US20120072124A1 - Genes associated with progression and response in chronic myeloid leukemia and uses thereof - Google Patents

Abstract

The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

Description

CROSS REFERENCE TO RELATED APPLICATIONS
• This application is a divisional of U.S. patent application Ser. No. 11/640,517 filed Dec. 14, 2006 which claims the benefit, under 35 U.S.C. §19(e), of U.S. Provisional Patent Application No. 60/751,455, filed on Dec. 15, 2005. Each of which is incorporated herein by reference in its entirety.
• This invention was made with U.S. Government support under Contract Nos. CA-18029 and CA-85053 awarded by the National Institutes of Health of the United States Department of Health and Human Services. The U.S. Government has certain rights in the invention.
• This application includes the Sequence Listing submitted in the parent application, entitled “Genes Associated with Progression and Response in Chronic Myeloid Leukemia and Uses Thereof” Ser. No. 11/640,517, filed Dec. 14, 2006, which is hereby incorporated by reference herein in its entirety.
TECHNICAL FIELD
• The invention relates to molecular markers that are associated with the progression of chronic myeloid leukemia (CML). The invention also relates to methods and computer systems for evaluating the progression of CML based on these molecular markers. The present invention also relates to methods and compositions for treating CML patients by modulating the expression or activity of certain genes involved in CML progression and/or their encoded proteins. The invention further relates to methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate (Gleevec™)
BACKGROUND
• Chronic myeloid leukemia (CML) is a hematopoetic stem cell disease with distinct biological and clinical features. In humans, a majority of CML (about 95%) has been found to be associated with a chromosomal abnormality that involves a t(9;22)(q34;q11) translocation, which results in the expression of the BCR/ABL fusion gene (Philadelphia Chromosome or Ph). The rest is associated with either a cryptic translocation that is invisible on G-banded chromosome preparations or a variant translocation involving another chromosome or chromosomes as well aschromosomes 9 and 22. CML usually presents in the so-called chronic phase, in which the clonal expansion of mature myeloid cells leads to an elevated white blood cell (WBC) count. Without curative intervention chronic phase CML will invariably transform through a phase of “acceleration,” often heralded by the appearance of increased immature myeloid cells in the bone marrow and peripheral blood, as well as new cytogenetic changes in addition to the Ph chromosome. Progression then proceeds quickly to blast crisis, with immature blast cells overwhelming the production of normal hematopoetic elements. Blast crisis is highly resistant to treatment, with death generally occurring from infection and bleeding complications secondary to the absence of normal granulocytes and platelets. The median time from diagnosis of chronic phase CML to progression blast crisis is approximately 3-4 years but the range of timing is quite broad, encompassing from 0.5-15 years (Faderl et al., 1999, Ann Intern Med 131:207).
• There is a broad range of treatment options for CML. All treatments work far better on chronic phase disease than on accelerated or blast phase. The only known curative therapy for CML is stem cell transplantation, a complex and potentially toxic modality that carries a high potential for morbidity and mortality (Radich et al., 2003, Blood 102:31). Non-transplant therapy includes alpha interferon, which can produce a major reduction in the proportion of Ph positive cells and extend the natural history of the disease in approximately 10-20% of cases (Kantarjian et al., 1999, J Clin Oncol 17:284). The tyrosine kinase inhibitor, imatinib mesylate, suppresses the Ph to the point where it is undetectable by cytogenetic evaluation (“complete cytogenetic remission”) in >70% of newly diagnosed chronic phase CML cases (Druker et al., 2001, N Engl J Med 344:1031). The duration of such responses is unknown, as is potential for cure with imatinib. Resistance to imatinib occurs (especially in advanced phase disease) often accompanied by point mutations in the active area of imatinib binding in the abl gene (Shah et al., 2002, Cancer Cell 2:117). The natural history of such relapses is unknown, though some appear to have a speedy entry into advanced disease (Branford et al., 2003, Blood 102:276).
• U.S. Patent Application Publication No. 2003/0104426 A1 discloses genetic markers whose expression correlates with progression of CML. Specifically, the patent application discloses sets of markers whose expression patterns can be used to differentiate chronic phase individuals from those in blast crisis, and methods of using these markers to distinguish these conditions. The patent application also discloses kits containing ready-to-use microarrays and computer data analysis software for carrying out the disclosed methods.
• PRAME (Preferentially Expressed Antigen of Melanoma) was identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729).
• The genetic events that cause the progression of chronic phase to blast crisis CML are unknown (Calabretta et al., 2004, Blood 103:4010; Shet et al., 2002, Leukemia 16:1402). Numerous genetic abnormalities have been demonstrated, including chromosomal changes including a multiplication of the Ph, the disruption of TP53, the deletion of the p15/p16 tumor suppressor genes (the latter only in lymphoid blast crisis). However, none of these changes are particularly common. Genetic instability is apparent in the additional chromosomal changes that occur with progression, though standard assays of instability, such as alterations in minisatellite repeats, is relatively uncommon (Wada et al., 1994, Blood 83:3449; Mori et al., 1997, Leukemia 11:151). Unfortunately, clinical and molecular tests cannot predict where on the “clock” of progression an individual lies at the time of the initial diagnosis, and this makes it impossible to tailor therapy to the degree of risk that faces an individual CML patient. It is also not possible to identify the subset of patients who will benefit most from the variety of therapy options, such as interferon, imatinib, or transplantation. Thus, presently tailoring therapy to individual risk is difficult. There is therefore a need to identify genes whose levels of expression change during the evolution of the chronic phase to blast crisis. There is a need for methods that utilize measured expression levels of such genes to determine the phase and/or progression of CML in a patient. There is also a need for methods of treating CML by targeting such genes.
• Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.
SUMMARY
• The invention provides a method for determining the progression of chronic myeloid leukemia (CML) in a patient, comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as a chronic phase (CP-CML) profile or as an advanced phase (ADV-CML) profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 1a and/or Table 1b or respective functional equivalents thereof, wherein at least one of said 5 genes is from Table 1a; and (b) determining said patient as in a chronic phase if said marker profile is classified as a CP-CML profile, or determining said patient as in an advanced phase if said marker profile is classified as an ADV-CML profile. In one embodiment, said plurality of gene products are of at least 5, 10, 20, 50, 70 or 100 of the genes listed in Table 1a. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.
• In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.
• In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 500 of the genes, respectively, listed in Table 1a and/or 1b.
• In another preferred embodiment, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 2a.
• In still another preferred embodiment, said gene products are products of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all of the genes, respectively, corresponding to the markers listed in Table 3. In one embodiment, said gene products are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the up-regulated markers listed in Table 3, or are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the down-regulated markers listed in Table 3.
• In one embodiment, each of said gene products is a gene transcript.
• In one embodiment, measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.
• In another embodiment, measurement of each said gene transcript is obtained by quantitative reverse transcriptase PCR (qRT-PCR).
• In another embodiment, each of said plurality of gene products is a protein.
• In a preferred embodiment, said classifying is carried out using a progression classifier, which receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is a CP-CML profile or an ADV-CML profile.
• In one embodiment, said progression classifier is trained with training data from a plurality of training CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is in CP-CML or ADV-CML.
• In a preferred embodiment, said progression classifier comprises a CP-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having CP-CML and/or an ADV-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having ADV-CML, and said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and/or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template and/or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template and/or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
• In a specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
• In another specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a higher similarity to said CP-CML template than to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a higher similarity to said ADV-CML template than to said CP-CML template.
• In one embodiment, said similarity to said CP-CML template is represented by a correlation coefficient between said marker profile and said CP-CML template, wherein said similarity to said ADV-CML template is represented by a correlation coefficient between said marker profile and said ADV-CML template. In one embodiment, said correlation coefficients between said marker profile and said CP-CML template and said ADV-CML template are respectively calculated according to the equation
• 
  P_i=({right arrow over (z)}_i·{right arrow over (y)})/(∥{right arrow over (z)}_i∥·∥{right arrow over (y)}∥)
• where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}₁represents said CP-CML template, and {right arrow over (z)}₂represents said ADV-CML template, P₁represents said correlation coefficient between said marker profile and said CP-CML template, and P₂represents said correlation coefficient between said marker profile and said ADV-CML template.
• In one embodiment, the measurement of each gene product in said CP-CML template or said ADV-CML template is an average of the measurements of said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.
• In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said CP-CML template is a relative level of said gene product representative of level of said gene product in a plurality of CP-CML patients versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said ADV-CML template is a relative level of said gene product representative of level of said gene product in a plurality of ADV-CML patients versus level of said gene product in a reference pool, represented as a log ratio.
• In one embodiment, the respective log ratio for each gene product in said CP-CML template or said ADV-CML template is an average of the log ratios for said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.
• In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).
• The invention also provides a method for assigning a therapeutic regimen for a CML patient, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning said patient a therapeutic regimen according to the status of progression determined in step (a). In one embodiment, said patient is determined to be in ADV-CML, and said therapeutic regimen assigned to said patient comprises bone marrow transplant.
• The invention also provides a method for enrolling CML patients for a clinical trial of an agent for treating CML, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning each patient having a CP-CML to one patient group and each patient having an ADV-CML to another patient group, at least one of said patient group being enrolled in said clinical trial.
• The invention also provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) determining the progression of said patient using any of the above described methods; and (b) determining said patient as responsive to IM treatment if said marker profile is classified as a CP-CML profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an ADV-CML profile.
• In another aspect, the invention provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as an IM-sensitive profile or an IM-resistant profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 4 or respective functional equivalents thereof; and (b) determining said patient as responsive to IM treatment if said marker profile is classified as an IM-sensitive profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an IM-resistant profile. In one embodiment, said plurality of gene products are of at least 5 of the genes listed in Table 4. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.
• In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.
• In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 4.
• In one embodiment, each of said gene products is a gene transcript.
• In one embodiment, measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.
• In another embodiment, each of said plurality of gene products is a protein.
• In a preferred embodiment, said classifying is carried out by a method comprising using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is an IM-sensitive profile or an IM-resistant profile.
• In one embodiment, said progression classifier is trained with training data from a plurality of tranining CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is sensitive or resistant to imatinib mesylate.
• In one embodiment, said progression classifier comprises an IM-sensitive template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients responsive to IM treatment and/or an IM-resistant template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients resistant to IM treatment, and said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and/or said IM-resistant template; and (a2) classifying said marker profile as a IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template and/or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template and/or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
• In a specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template or said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
• In another specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a higher similarity to said IM-sensitive template than to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a higher similarity to said IM-resistant template than to said IM-sensitive template.
• In one embodiment, said similarity to said IM-sensitive template is represented by a correlation coefficient between said marker profile and said IM-sensitive template, and said similarity to said IM-resistant template is represented by a correlation coefficient between said marker profile and said IM-resistant template.
• In one embodiment, said correlation coefficients between said marker profile and said IM-sensitive template and said IM-sensitive template are respectively calculated according to the equation
• 
  P_i=({right arrow over (z)}_i·{right arrow over (y)})/(∥{right arrow over (z)}_i∥·∥{right arrow over (y)}∥)
• where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}₁represents said IM-sensitive template, and {right arrow over (z)}₂represents said IM-resistant template, P₁represents said correlation coefficient between said marker profile and said IM-sensitive template, and P₂represents said correlation coefficient between said marker profile and said IM-resistant template.
• In one embodiment, the measurement of each gene product in said IM-sensitive template or said IM-resistant template is an average of the measurements of said gene product in a plurality of patients responsive to IM treatment or in a plurality of patients resistant to IM treatment, respectively.
• In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said IM-sensitive template is a relative level of said gene product representative of level of said gene product in a plurality of patients responsive to IM treatment versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said IM-resistant template is a relative level of said gene product representative of level of said gene product in a plurality of patients resistant to IM treatment versus level of said gene product in a reference pool, represented as a log ratio.
• In one embodiment, the respective log ratio for each gene product in said IM-sensitive template or said IM-resistant template is an average of the log ratios for said gene product in a plurality of patients responsive to IM treatment or in a plurality of ADV-CML patients, respectively.
• In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).
• The invention also provides a method for assigning a treatment regimen for a CML patient, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning said patient a treatment regimen comprising bone marrow transplant if said patient is determined to be resistant to imatinib mesylate.
• The invention also provides a method for enrolling CML patients for a clinical trial of a treatment modality for treating CML, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning each patient who is predicted to be resistant to imatinib mesylate to one patient group and each patient who is predicted to be responsive to imatinib mesylate to another patient group, at least one of said patient group being enrolled in said clinical trial.
• In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising one or more agents that modulate the expression and/or activity of one or more different genes listed in one or more of Tables 2a, 2b, 5a and 5b and/or their encoded proteins, wherein said patient exhibits aberrant regulation of said one or more genes.
• In one embodiment, said one or more different genes are selected from the different genes listed in one or more of Tables 2a and 5a.
• In another embodiment, said one or more different genes are selected from the genes listed in both Tables 2a and 5a, i.e., genes common in Tables 2a and 5a.
• In still another embodiment, said one or more different genes are selected from the genes listed in Table 3.
• In one embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more different genes in said patient.
• In another embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more different genes in said patient.
• In a preferred embodiment, said treatment regimen comprises an siRNA targeting said one or more different genes.
• In preferred embodiment, said one or more different genes consisting of 2, 3, 4, 5, 6, or 10 different genes.
• In another embodiment, said one or more different genes are selected from the down-regulated genes listed in Table 3, and said treatment regimen comprises subjecting said patient to gene therapy, said gene therapy enhancing the expression of said one or more different genes in said patient.
• In one embodiment, the methods of the invention further comprises determining a transcript level of each of said one or more different genes, and said patient is determined to exhibit aberrant regulation of said different gene if said transcript level deviated from a predetermined threshold level. In some embodiments, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.
• In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene. In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.
• In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using quantitative reverse transcriptase PCT (qRT-PCR).
• In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising (i) an effective amount of imatinib mesylate (IM), and (ii) an agent other than IM, wherein said agent modulates the expression and/or activity of 1, 2, 3, 4, 5, 10 or more of the genes listed in Table 4 and/or their encoded proteins, and wherein said patient exhibits aberrant regulation of said one or more genes.
• In one embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more genes in said patient.
• In another embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more genes in said patient.
• In one embodiment, said treatment regimen comprises an siRNA targeting said one or more target genes.
• In some embodiments, said one or more genes consists of at least 2, 3, 4, 5, 6, or target genes.
• In one embodiment, said one or more genes are selected from the group consisting of the down-regulated genes listed in Table 4, and said agent comprises subject said patient to gene therapy, said gene therapy enhancing the expression of said one or more genes in said patient.
• The methods can further comprises determining a transcript level of each said gene, and said patient is determined to exhibit aberrant regulation of said gene if said transcript level deviated from a predetermined threshold level. In some embodiment, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.
• In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene.
• In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.
• In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said CML target gene using quantitative reverse transcriptase PCT (qRT-PCR).
• In still another aspect, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting cells a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a label; and (b) detecting said label on said cells, wherein detection of said label above a predetermined threshold indicates that said patient has advanced phase CML. The cell sample can be a bone marrow sample or a peripheral blood sample.
• In one embodiment, said antibody is a monoclonal antibody.
• In another embodiment, said label is fluorescence label, and said detecting is carried out using a fluorescence activated cell sorter.
• In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody, wherein said antibody binds a PRAME protein, and wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a therapeutic molecule, wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells.
• In one embodiment, said antibody is a monoclonal antibody.
• The invention also provides a method for ex vivo depletion of advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of a patient, comprising (a) incubating said bone marrow or peripheral blood sample with an antibody that binds a PRAME protein; and (b) removing cells having said antibody attached. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising (i) depleting advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of said patient using the method described above; and (ii) transplanting the sample obtained in step (i) to said patient.
• In still another aspect, the invention provides a method for identifying a set of genes that are associated with progression of chronic myeloid leukemia (CML), comprising: (a) subtracting from each of a plurality of CML expression profiles a CD34+ expression profile to obtain a plurality of CD34+(−) CML expression profiles, each said CML expression profile comprising levels of expression of a plurality of genes in cells of one of a plurality of chronic myeloid leukemia (CML) patients, said CD34+ expression profile comprising levels of expression of said plurality of genes in non cancerous immature CD34+ cells, said plurality of CML patients comprising patients of different phases of CML; (b) comparing said plurality of CD34+(−) CML expression profiles; and (c) identifying one or more genes that exhibit significant differences in levels of expression between different phases of CML across said plurality of CD34+(−) CML expression profiles.
• In one embodiment, said comparing is carried out by ANOVA and said identifying is carried out by identifying one or more genes one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p<10⁻⁸.
• The method can further comprise: (d) comparing levels of expression of said identified genes between cells of CML blast crisis and normal immature CD34+ cells; and (e) selecting those genes that exhibit significant differences in expression.
• In another embodiment, said comparing is carried out by ANOVA and said selecting is carried out by selecting one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p-value <0.01%.
• The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs, wherein said one or more programs cause the processor to carry out any one of the methods of the invention.
• The invention also provides a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, said computer program product comprising a computer readable storage medium having a computer program mechanism encoded thereon, wherein said computer program mechanism may be loaded into the memory of said computer and cause said computer to carry out any one of the methods of the invention.
• In still another aspect, the invention provides a microarray comprising for each of a plurality of genes, said genes being at least 5 of the genes selected from the group consisting of the genes as identified respectively by SEQ ID NOS: 1-3968, wherein at least one of said 5 genes is not a gene selected from the group consisting of genes as identified respectively by SEQ ID NOS: 56, 65, 70, 177, 190, 199, 1758, 1773, 1774, 1776, 1786, 1815, 1823, 3925, 3933, 3947, 3956, and 3961, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 70%, 80%, 90% or 98% of the probes on said microarray.
• In one embodiment, said plurality of genes is at least 10, 20, 40, 70, 100, or 200 genes.
• In another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 1a and/or 1b.
• In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 2a and/or 2b.
• In still another embodiment, said plurality of genes is at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all 20 of the genes listed in Table 3.
• In still another embodiment, said plurality of genes are selected from the group consisting of the genes listed in Table 4.
• In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 5a and/or 5b.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1. Genes associated with CML progression. Samples of CML cases in chronic phase, accelerated by cytogenetic criteria only, accelerated phase, blast crisis, and blast crisis “in remission” were compared to a pool of chronic phase RNA. Approximately 3,000 genes were significantly associated with progressive disease at a significance level of p<10⁻¹¹. Each row represents one sample, and each column represents one gene. A darker color indicates over-expression relative to the control pool, and a lighter color indicates low-expression.
• FIG. 2. 2a: Genes differentially expressed in blast crisis CML compared to normal CD34+ stem cells. CML blast crisis samples with >70% blasts were compared to normal CD34+ bone marrow stem cells.2b: Approximately 400 genes were significantly differentially expressed between CML blasts and their immature CD34+ normal counterparts (ANOVA P<0.1%).2c: Phase genes corrected for normal CD34+ gene expression (ANOVA P<1×10⁻⁸). The gene expression of normal CD34+ cells was subtracted from each disease sample. The resulting pattern reflects genes associated with progression independent of normal blast biology.
• FIG. 3. Genes expression signature of genes associated with specific promoter sequences. Genes with specific promoter sequences were tested for their differential enrichment across different phases of CML (see Methods).FIG. 3ashows genes bearing a MZF promoter;FIG. 3bshows expression of genes under putative control of delta EF1.
• FIG. 4. Gene expression in Imatinib failure cases.4a: All CML cases including cases of imatinib failure; gene expression is based on the previously obtained ˜3,000 phase reporter set.4b: Cases are ranked and sorted by the correlation of summed gene expression, with cases representing the most “cp-like” and most “bc-like” forming the boundaries of gene expression patterns. Cases of imatinib failures are shown.4c: Genes differentially expressed in imatinib resistant cases that are not associated with progression gene set. The boxed areas represent genes differentially expressed in the imatinib resistant cases compared to blast crisis cases.
• FIG. 5. Comparison of gene expression in accelerated phase versus blast phase CML. The graph shows the scatter plot of log(ratio) of all 25K genes in blast crisis and accelerated phase cases. Each blue dot represents a gene. Thus, genes in the upper left hand box are up in accelerated phase, but down in blast crisis. Genes in the upper right box are up both in accelerated and blast crisis. The gene expression levels are very highly correlated between accelerated and blast crisis (r=0.81).
• FIG. 6. Phase reporter genes after removal of normal CD34+ signature. The gene expression signature of normal CD34+ cells was subtracted from the data of CML cases. The genes shown are the genes differentially expressed across disease phases after genome wide removal of CD34+ signatures (p-value of <10⁻⁴).
• FIG. 7. Comparison of gene expression between bone marrow and peripheral blood. In three cases of blast crisis samples were simultaneously drawn from marrow and blood. The figures show a high correlation of gene expression for these three cases.
• FIG. 8 illustrates an exemplary embodiment of a computer system for implementing the methods of this invention.
DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
• The invention provides molecular markers, i.e., genes, the expression levels of which can be used for evaluating the progression of chronic myeloid leukemia (CML) from chronic phase to advanced phase. The identities of these markers and the measurements of their respective gene products, e.g., measurements of levels (abundances) of their encoded mRNAs or proteins, can be used by application of a pattern recognition algorithm to develop a progression classifier that discriminates between different phases of CML based on measurements of such gene products in a sample from a patient. As used herein, the term “gene product” includes mRNA transcribed from the gene and protein encoded by the gene.
• Chronic myelogenous leukemia (CML) is characterized by high peripheral white blood cell (WBC) counts with granulocyte predominance and extramedullary hematopoiesis. CML typically evolves through 3 clinically distinct stages or phases: chronic phase (CP-CML or CP), accelerated phase (AP-CML or AP), and blast phase (BP-CML or BP), which is also called acute phase or blast crisis (BC-CML or BC). The chronic phase lasts several years and is characterized by accumulation of myeloid precursors and mature cells in bone marrow, peripheral blood, and extramedullary sites. During the chronic phase, patients typically have fewer than 10% blasts (or 20% blasts and promyelocytes combined) in blood or bone marrow samples. These patients usually have relatively mild symptoms and usually respond to standard treatments. The chronic phase progresses into the accelerated phase, which lasts about 4 to 6 months. During the accelerated phase, patients typically have more than 10% blasts (or 20% blasts and promyelocytes combined) but less than 30% blasts and promyelocytes in their bone marrow or blood samples. These patients often have fever, poor appetite, and weight loss. Symptoms and blood counts of an AP-CML patient are not as responsive to treatments as they are during the chronic phase. The leukemia cells often have developed new chromosomal changes, in addition to the Philadelphia chromosome. The accelerated phase progresses to the blast phase, which lasts for a few months. During the blast phase, patients typically have more than 30% blasts and promyelocytes in their bone marrow and/or blood samples. The blast cells often spread to tissues and organs beyond the bone marrow. The accelerated phase and the blast phase are often grouped together into an advanced phase of CML (ADV-CML or ADV). The molecular markers of the invention are particular useful for evaluating the progression of a CML patient from the chronic phase to the advanced phase.
• The invention provides a list of genes that are differentially expressed across different phases of CML (Tables 1a and 1b, infra). This set of genes is called the phase reporter geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for staging a CML patient. A functional equivalent with respect to a gene, designated as gene A, refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA encoded by gene A. In particular, CML staging in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a and/or 1b; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a and/or 1b, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 1a. Such a profile of measurements is also referred to herein as an “expression profile” or a “marker profile.” In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a, or functional equivalents of such genes. In another specific embodiment, the evaluation of CML progression in a patient is carried out using measurements of gene products of less than 30, 40, 50, 70, 100, 200, 300, 400, or 500 total genes, in which all or at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes are from Tables 1a and/or 1b or their functional equivalents, or at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 of the genes are from Tables 1a and/or 1b or their functional equivalents. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelerated phase or blast crisis).
• The invention also provides a list of genes that are associated with CML progression (Tables 2a and 2b, infra). These genes are also termed “progression genes” in the application. This set of genes is called the progression geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for staging a CML patient. Since these genes are associated with CML progression, they are also targets for therapeutic intervention of CML. For example, a CML patient exhibiting aberrant regulation of such genes can be treated by therapies targeting such genes. Thus, measurements of gene products of these molecular markers, as well as of their functional equivalents, can also be used for determining an appropriated treatment regimen for a CML patient.
• Different subcombination of CML progression genes can also be used. Thus, in various embodiments, the markers that are the genes listed in Tables 2a-2b or 3 are used. Measurements of gene products of these molecular markers and/or their functional equivalents can be used for evaluating the progression of CML in a patient. The evaluation of CML progression in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Tables 2a and/or 2b, or at least 5, 10, 15 or all of the genes in Table 3; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a and/or 2b or in Table 3, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 2a. In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 300 or all of the genes in Tables 2a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a, or functional equivalents of such genes. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelerated phase or blast crisis).
• The invention also provides a list of genes that are associated with resistance to imatinib mesylate (Table 4, infra). These genes are also termed “imatinib resistance genes” in the application. This set of genes is called the imatinib resistance geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for evaluating the responsiveness of a CML patient to imatinib treatment. The evaluation of responsiveness of a patient to imatinib is carried out by a method comprising determining whether the patient is likely to be responsive to imatinib treatment based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Table 4; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Table 4, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient. In one embodiment, if the patient expression profile is classified as a IM-resistance profile, the patient is determined as likely to be resistant to imatinib treatment, whereas if the patient expression profile is classified as a IM-sensitive profile, the patient is determined as likely to be responsive to imatinib treatment. In a specific embodiment, a CML patient in the chronic phase is evaluated for responsiveness to imatinib treatment based on an expression profile of such imatinib resistance genes. If the patient's expression profile indicates that the patient is likely to be resistant to imatinib treatment, bone marrow transplantation and/or other investigative treatment regimens may be assigned to the patient.
• In another embodiment, the responsiveness of a CML patient to imatinib treatment can also be evaluated based on expression of phase reporters or progression genes. In this embodiment, the patient expression profile comprising measurements of phase reporter genes (Table 1a and/or 1b) or progression genes (Table 2a and/or 2b) is evaluated using a method described above. If the patient expression profile is classified as a ADV-CML profile, the patient is determined as likely to be resistant to imatinib treatment.
• The measurements in the profiles of the gene products that are used can be any suitable measured values representative of the expression levels of the respective genes. The measurement of the expression level of a gene can be direct or indirect, e.g., directly of abundance levels of RNAs or proteins or indirectly, by measuring abundance levels of cDNAs, amplified RNAs or DNAs, proteins, or activity levels of RNAs or proteins, or other molecules (e.g., a metabolite) that are indicative of the foregoing. In one embodiment, the profile comprises measurements of abundances of the transcripts of the marker genes. The measurement of abundance can be a measurement of the absolute abundance of a gene product. The measurement of abundance can also be a value representative of the absolute abundance, e.g., a normalized abundance value (e.g., an abundance normalized against the abundance of a reference gene product) or an averaged abundance value (e.g., average of abundances obtained at different time points or from different tumor cell samples from the patients, or average of abundances obtained using different probes, etc.), or a combination of both. As an example, the measurement of abundance of a gene transcript can be a value obtained using an Affymetrix® GeneChip® to measure hybridization to the transcript.
• In another embodiment, the expression profile is a differential expression profile comprising differential measurements of a plurality of transcripts in a sample derived from the patient versus measurements of the plurality of transcripts in a reference sample, e.g., a cell sample of normal cells. Each differential measurement in the profile can be but is not limited to an arithmetic difference, a ratio, or a log(ratio). As an example, the measurement of abundance of a gene transcript can be a value for the transcript obtained using an ink-jet array or a cDNA array in a two-color measurement. In a preferred embodiment, the reference sample comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML). In another preferred embodiment, the reference sample comprise target polynucleotide molecules from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.
• The invention also provides methods and computer systems for evaluating the progression of CML in a patient based on a measured marker profile comprising measurements of the markers of the present invention, e.g., an expression profile comprising measurements of transcripts of at least some of the genes listed in Tables 1a and/or 1b, e.g., at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 in Tables 1a and/or 1b or functional equivalents of such genes, wherein at least 1, 2, 3, 5 or 10 genes are from Table 1a. The methods and systems of the invention use a progression classifier for evaluating the progression of CML. The progression classifier can be based on any appropriate pattern recognition method (such as those described in Section 5.2) that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs, i.e., chronic phase or advanced phase. The progression classifier can be constructed with training data from a plurality of CML patients for whom marker profiles and progression status are known. The plurality of patients used for training the progression classifier is also referred to herein as the training population. The training data comprise for each patient in the training population (a) a marker profile comprising measurements of gene products of a plurality of genes, respectively, in an appropriate cell sample, e.g., a bone marrow or peripheral blood sample, taken from the patient; and (b) progression status information (e.g., the CML phase of the patient). Various progression classifiers that can be used in conjunction with the present invention are described in Section 5.2., infra. In some embodiments, additional patients having known marker profiles and progression status can be used to test the accuracy of the progression classifier obtained using the training population. Such additional patients are also called “the testing population.”
• The markers in the marker sets are selected based on their ability to discriminate patients having different CML phases in a plurality of CML patients for whom the progression status are known. Various methods can be used to evaluate the correlation between marker levels and CML progression. For example, genes whose expression levels are significantly different across patients in different CML phases can be identified using an appropriate statistical method, e.g., ANOVA.
• The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, the expression and/or activities of one or more CML progression genes and/or target genes and/or their gene products. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain CML pathways that involve in CML progression and response. The CML progression genes include those genes listed in Tables 2a and 2b. The CML target genes include those genes listed in Tables 5a and 5b. The CML pathways include FLT3; Rras2; beta-catenin; and SOCS2. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain proteosomes and chaperone proteins. The invention also provides methods and compositions for treating a patient having CML by modulating genes controlled by a promoter selected from the group consisting of the following MZF, delta EF1, SPI-B, Yin Yang, and Ahr-ARNT. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., reducing, the expression and/or activity of CD47. The invention also provides methods and compositions for treating a patient having CML by targeting PRAME. The invention is based, at least in part, on the identification of aberrant regulation of these genes and pathways in CML.
• Thus, the invention provides methods and compositions for treating CML by modulating the expression and/or activity of CML progression genes and/or CML target genes and/or their gene products, and/or by modulating interactions of the CML progression genes and/or target genes and/or their gene products with other proteins or molecules, e.g., substrates. The methods and compositions can be used for treating CML patient who exhibit aberrant regulation in such CML progression/target genes. Thus, such methods and compositions can be used in conjunction with imatinib mesylate. In one embodiment, the expression of one or more of the CML progression/target genes is modulated, e.g., reduced or enhanced, to treat a CML patient exhibiting aberrant regulation of these CML progression/target genes. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the CML progression/target genes. In another embodiment, the activity of one or more CML progression/target proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target a CML progression/target protein.
• The invention also provides methods and compositions for treating CML by modulating the expression and/or activity of imatinib mesylate resistance genes and/or their gene products, and/or by modulating interactions of the IM-resistance genes and/or their gene products with other proteins or molecules, e.g., substrates, in combination of imatinib mesylate. In one embodiment, the expression of one or more of the IM-resistance genes is modulated, e.g., reduced or enhanced, to treat a CML patient undergoing imatinib mesylate treatment. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the imatinib mesylate genes. In another embodiment, the activity of one or more imatinib mesylate proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target imatinib mesylate proteins.
• The invention also provides methods and compositions for utilizing CML progression/target genes or IM-resistance genes, and/or their products for screening for agents that modulate their expression and/or activity and/or modulating their interactions with other proteins or molecules. Agents that modulate expression and/or activity of CML progression/target genes can be used for treating CML patient exhibiting aberrant regulation of one or more CML progression/target genes. Agents that modulate expression and/or activity of IM-resistance genes can be used in combination with IM for treating CML patient exhibiting resistance to IM treatment. Thus, the invention provides methods and compositions for utilizing CML progression/target genes and gene products for screening for agents that are useful in modulating expression and/or activity of CML progression/target genes or IM resistance genes and/or their products and/or modulating their interactions with other proteins or molecules in a CML patient exhibiting aberrant regulation of one or more CML progression/target genes or IM resistance genes. The compositions of the invention include but not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, peptide or polypeptide molecules, and small organic or inorganic molecules.
• The present invention also provides methods and compositions for identifying other extra- or intra-cellular molecules, e.g., genes and proteins, which interacts with the CML progression/target genes or IM resistance genes, and/or their gene products, and/or CML progression pathways. The present invention also provides methods and compositions for treating CML by modulating such cellular constituents and/or pathways.
• As used herein, a patient is an animal having CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In a preferred embodiment, the patient is a human patient. Suitable samples that can be used in conjunction with the present invention include but are not limited to bone marrow samples and peripheral blood samples.
5.1. Genes Associated with CML Progression and Response
• The invention provides molecular marker sets (of genes) that can be used for evaluating progression and/or imatinib resistance in a CML patient based on a profile of the markers in the marker set (containing measurements of marker gene products).
• Tables 1a and 1b list genes that are differentially expressed across different phases of CML. This set of genes is called the phase reporter geneset. The phase reporter genes are identified by their SEQ ID NOs in Tables 1a and 1b. Tables 1a and 1b also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase. Information for these genes is presented in Table 8. In Table 8, the following information is presented for each gene: gene identifier (column 1), gene name (column 2), the SEQ ID NO of the sequence of the gene (column 3), and the SEQ ID NO of the probe sequence used in the present application (column 4). The first column of Table 8 shows the identifiers of genes disclosed in the application. The term “SUBS” is shorthand for substance identifier. For those genes listed in Table 8 that have a GenBank® accession number, the GenBank® accession number is listed. For those genes in Table 8 that do not have a GenBank® Accession No, the Contig ID numbers of the transcript sequences in the Phil Green assembly (Nat Genet. 2000 June; 25(2):232-4) is listed. Phil Green's group at the University of Washington assembled ESTs from the Washington University-Merck Human EST Project and CGAP archives. Analysis of expressed sequence tags indicates 35,000 human genes (Nat Genet. 2000 June; 25(2):232-4). This assembly, dated Mar. 17, 2000, resulted in 62,064 contigs representing 795,000 ESTs. These contigs have the word “contig” included in their identifiers. Table 1a lists phase reporters that were not disclosed in U.S.Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 1b lists phase reporters that were also identified in U.S.Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.

• TABLE 1a
  phase reporter genes

  	SEQ ID NO	log(ratio) CP	log(ratio) AP	log(ratio) BC

  	1	−0.00406	0.196563	0.331631
  	2	−0.013036	0.331191	0.13619
  	3	−0.01517	−0.1969	−0.51997
  	4	−0.01226	0.234703	0.506317
  	5	−0.01055	−0.11513	−0.25239
  	6	0.02333	0.2234	0.385294
  	7	0.001109	−0.04225	−0.38922
  	8	0.022178	0.320491	0.362686
  	9	−0.01332	−0.22505	−0.26552
  	10	0.002491	0.107514	0.40248
  	11	−0.03342	−0.12983	−0.34856
  	12	−0.02396	−0.1739	−0.56037
  	13	0.004316	−0.16534	−0.15954
  	14	−0.00225	0.464357	0.637155
  	15	−0.06413	−0.10146	−0.58794
  	16	0.009128	0.235874	0.469511
  	17	0.020236	1.123603	0.742981
  	18	0.016214	0.159637	0.392829
  	19	−0.04723	−0.47509	−1.36264
  	21	−0.01095	0.232221	0.294685
  	22	0.012172	0.427707	0.729027
  	23	−0.01999	−0.21291	−0.36149
  	24	−0.00972	−0.14706	−0.4052
  	25	0.004981	−0.21328	−0.37135
  	26	−0.02611	−0.30231	−0.45226
  	27	0.010514	0.338824	0.434019
  	29	−0.02088	−0.283	−0.45987
  	30	−0.00198	−0.11265	−0.28724
  	31	0.023577	0.770737	0.690215
  	32	0.008671	−0.0801	−0.28421
  	33	0.012103	−0.15124	−0.15019
  	34	0.010651	−0.14341	−0.515
  	35	−0.00126	0.010489	0.264385
  	36	0.027348	0.34774	0.624742
  	37	0.033762	0.213053	0.520588
  	38	0.003765	−0.14306	−0.39624
  	39	0.033025	0.281292	0.406565
  	40	−0.06315	−0.28017	−1.14257
  	41	0.007748	0.09581	0.335903
  	42	−0.01732	−0.09377	−0.68791
  	43	0.018086	−0.22492	−0.285
  	44	0.014232	−0.27373	−0.31289
  	45	0.036197	0.142295	0.466937
  	46	−0.01022	0.299737	0.425197
  	47	0.006822	0.199214	0.443601
  	48	0.021602	0.186392	0.33675
  	49	−0.03649	−0.26722	−0.49009
  	52	0.008248	0.502971	0.507442
  	53	0.040187	0.687502	0.564688
  	54	−0.00051	−0.10576	−0.40709
  	55	−0.01352	−0.22612	−0.49128
  	57	−0.05265	0.433648	0.40219
  	58	0.019239	0.187127	0.325353
  	59	0.006451	−0.22186	−0.18506
  	60	0.010201	0.615117	1.017473
  	61	0.013254	−0.23449	−0.26153
  	62	0.012036	−0.20146	−0.36216
  	63	0.018656	0.262829	0.530868
  	64	−0.01623	−0.1428	−0.50841
  	66	−0.00346	−0.1026	−0.30257
  	67	0.009841	0.335299	0.527591
  	68	0.009665	0.97143	0.990692
  	69	−0.03517	0.36588	0.442864
  	71	0.005961	−0.17466	−0.20803
  	73	−0.00646	−0.25708	−0.21749
  	74	−0.018621	0.110352	−0.541362
  	75	−0.00408	−0.21342	−0.26897
  	76	0.009207	0.769453	0.850508
  	78	0.0123	0.167805	0.337085
  	79	0.00674	−0.17218	−0.25414
  	80	−0.00232	−0.13768	−0.25962
  	81	−0.04268	−0.09565	−0.76123
  	82	−0.00889	−0.18131	−0.3448
  	83	0.00964	0.139417	0.328274
  	84	−0.03477	0.147022	−0.67052
  	85	−0.0546	−0.22956	−1.32988
  	86	−0.01987	−0.41057	−0.63814
  	87	−0.00053	−0.16512	−0.19246
  	89	0.029134	0.166704	0.399066
  	90	−0.00832	−0.13645	−0.3186
  	92	0.037155	0.284153	0.64532
  	94	−0.01142	−0.13881	−0.3608
  	95	0.01125	0.10955	0.227757
  	96	0.012527	0.229295	0.293851
  	98	0.060257	0.952532	0.999368
  	100	−0.0643	−0.33585	−0.59098
  	101	0.009363	0.184372	0.293381
  	102	−0.0128	−0.2329	−0.54422
  	103	0.019799	0.472863	0.54563
  	104	0.039449	0.415733	0.576671
  	106	0.010496	−0.12076	−0.18666
  	107	0.011423	−0.16555	−0.23653
  	108	−0.08443	1.178885	0.802082
  	109	0.013994	0.264328	0.401994
  	110	0.04438	0.40653	0.580366
  	111	0.027108	0.265955	0.604212
  	112	0.003332	−0.25986	−0.29846
  	113	−0.01029	−0.26712	−0.2846
  	114	−0.05586	−0.21334	−0.82293
  	115	0.009594	0.017981	0.208686
  	117	−0.01023	0.452998	0.673941
  	118	−0.00659	0.490457	0.517515
  	119	−0.02254	0.744289	0.818592
  	120	−0.01441	−0.29009	−0.5309
  	121	−0.01153	−0.19616	−0.33788
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  	1743	0.010364	0.348908	0.367908
  	1744	−0.02434	−0.09144	0.156156
  	1745	−0.02231	−0.20802	−0.22645
  	1746	−0.04199	−0.25892	−1.00436
  	1747	−0.01659	−0.1995	−0.30164
  	1748	−0.03118	−0.26385	−0.39963
  	1749	0.001133	−0.16781	−0.22877
  	1750	−0.0074	−0.24548	−0.5296
  	1751	0.030846	0.50771	0.564782
  	1752	−0.0023	0.557287	0.447554
  	1753	0.044274	−0.18457	−0.17418
  	1754	0.005458	0.258669	0.438507
  	1755	0.026709	0.265936	0.433134
  	1756	−0.07289	−0.28387	−0.87405
  	1759	0.017564	0.231565	0.588896
  	1760	−0.00904	−0.20562	−0.2297
  	1761	0.034479	0.143745	0.281478
  	1763	0.002059	0.422689	0.661307
  	1764	0.015931	0.381083	0.601851
  	1765	−0.069608	0.229406	−0.942888
  	1766	−0.01109	0.23371	0.474147
  	1768	0.04507	0.229723	0.345461
  	1769	−0.07627	0.156128	0.250496
  	1770	0.01144	0.346982	0.490984
  	1771	−0.02162	−0.28795	−0.27807
  	1772	0.019225	0.236177	0.441341
  	1775	0.022918	0.183774	0.301866
  	1777	0.010911	0.118611	0.209198
  	1778	−0.05232	−0.2939	−1.18191
  	1779	0.011474	0.267102	0.353548
  	1780	0.032706	0.233902	0.480801
  	1782	−0.00163	−0.14093	−0.26973
  	1783	0.030167	0.180356	0.299337
  	1784	0.015401	0.594929	0.862064
  	1785	−0.00264	0.291894	0.36507
  	1787	−0.01282	−0.21492	−0.34306
  	1788	0.009731	−0.13302	−0.11645
  	1789	−0.00598	−0.0331	−0.28125
  	1790	0.008607	−0.16296	−0.20062
  	1791	0.002438	0.388732	0.329922
  	1792	0.001959	0.023872	0.208334
  	1793	0.010073	0.404828	0.426744
  	1794	−0.03895	−0.21887	−0.5835
  	1795	−0.0592	−0.09279	−0.44737
  	1796	−0.0262	−0.25466	−0.21655
  	1797	−0.12257	−0.31528	−1.5223
  	1798	0.006863	0.125618	0.179833
  	1801	0.002794	−0.12806	−0.33744
  	1802	−0.006187	−0.271892	−0.547214
  	1803	−0.02679	−0.23885	−0.46079
  	1804	0.007217	−0.21745	−0.20809
  	1805	−0.11509	−0.38375	−0.60223
  	1806	−0.02318	−0.33783	−1.07263
  	1807	−0.00505	−0.2652	−0.35813
  	1808	0.004754	0.169766	0.345844
  	1809	−0.01864	−0.17631	−0.30283
  	1810	−0.01537	−0.11929	−0.49832
  	1811	−0.02414	−0.22298	−0.56307
  	1812	−0.05789	−0.46577	−0.67116
  	1813	0.004929	0.074195	−0.38902
  	1814	−0.12994	−0.5422	−0.67394
  	1816	0.000462	−0.29172	−0.78629
  	1817	−0.05267	−0.08425	−0.56209
  	1818	0.021928	0.103957	0.612197
  	1819	−0.04001	−0.08007	−0.62152
  	1821	0.012366	0.608222	0.811802
  	1822	0.008709	0.058535	0.172787
  	1824	0.055901	1.019295	1.14166
  	1825	−0.01941	−0.32585	−0.35338
  	1826	0.024815	0.359143	0.586203
  	1827	−0.01719	−0.20544	−0.21855
  	1829	−0.0351	0.382362	0.463074
  	1830	0.012246	−0.22063	−0.17454
  	1831	−0.01595	−0.15761	−0.40073
  	1832	0.018962	0.22087	0.566994
  	1833	0.029653	0.034092	0.253365
  	1834	−0.01445	−0.24365	−0.30384
  	1835	−0.02682	−0.22033	−0.32568
  	1836	−0.09901	−0.30331	−1.47414
  	1837	0.030238	0.239652	0.470628
  	1838	0.002423	−0.19623	−0.5761
  	1841	−0.03342	−0.13149	−0.66763
  	1842	0.029358	0.337117	0.459639
  	1843	0.001903	−0.21172	−0.37406
  	1844	−0.03995	−0.30379	−0.41743
  	1845	−0.00479	−0.13037	−0.30756
  	1846	−0.00041	−0.34946	−0.65983
  	1847	−0.00414	−0.14024	−0.31772
  	1848	−0.01386	−0.22644	−0.32931
  	1850	0.01079	0.211982	0.326417
  	1851	−0.02231	−0.2043	−1.19046
  	1852	0.015181	0.111086	0.251967
  	1853	−0.01527	−0.28004	−0.47715
  	1854	0.000932	−0.24516	−0.28454
  	1855	0.033597	0.184815	0.265554
  	1856	−0.03302	−0.34634	−0.76554
  	1857	0.005193	−0.22844	−0.62729
  	1858	−0.05483	−0.30502	−0.82935
  	1859	0.001499	−0.10385	−0.32329
  	1860	0.013105	0.210462	0.248993
  	1861	0.008675	0.496561	0.927091
  	1862	0.010826	−0.21583	−0.30859
  	1863	−0.02181	−0.43456	−0.94264
  	1864	−0.01059	−0.24026	−0.50607
  	1865	−0.01382	0.374521	0.555237
  	1866	−0.12558	−0.46355	−1.21848
  	1867	0.016134	−0.25351	−0.57052
  	1868	0.001577	0.372509	0.34609
  	1869	−0.14247	−0.50568	−1.11469
  	1871	−0.03321	−0.44414	−1.2074
  	1872	0.022755	0.237358	0.526712
  	1874	0.015851	0.398675	0.461731
  	1875	0.028164	0.290971	0.40534
  	1876	−0.00363	0.330491	0.472481
  	1877	−0.01271	−0.28482	−0.41247
  	1878	−0.05324	−0.21202	−0.97494
  	1879	−0.01231	0.272185	0.50145
  	1880	0.009419	−0.16361	−0.28568
  	1881	0.024008	0.385428	0.510505
  	1882	−0.01343	−0.30202	−0.25117
  	1883	0.019995	0.230682	0.273889
  	1884	−0.0234	0.35963	0.444844
  	1885	0.026138	0.213097	0.383805
  	1886	−0.00891	0.004522	−0.56889
  	1887	−0.00744	−0.28972	−0.55691
  	1888	0.016743	0.303348	0.429235
  	1889	0.001491	0.145451	0.360623
  	1890	−0.00739	−0.14358	−0.51551
  	1891	−0.01196	−0.17613	−0.29865
  	1892	−0.04341	−0.18291	−1.32937
  	1894	0.036374	0.308875	0.347083
  	1895	−0.01486	−0.35427	−0.75272
  	1896	0.020399	−0.17097	−0.28996
  	1897	0.00121	−0.17923	−0.19633
  	1899	−0.02719	−0.20241	−0.70406
  	1900	−0.00544	−0.1899	−0.31452
  	1901	−0.02757	−0.18302	−1.14281
  	1902	0.002335	−0.21384	−0.30124
  	1903	0.022039	0.236533	0.451828
  	1904	−0.02356	−0.35422	−0.59893
  	1905	0.012193	0.149476	0.324708
  	1906	−0.018987	−0.066969	−0.26783
  	1907	0.006033	0.110037	0.284895
  	1908	0.001763	−0.19256	−0.24906
  	1909	−0.03746	−0.27994	−0.98912
  	1910	−0.014553	−0.104128	−0.202699
  	1911	−0.00195	−0.19606	−0.26083
  	1912	−0.00425	−0.25347	−0.32548
  	1913	−0.09292	−0.0302	−0.94519
  	1914	−0.01006	−0.17543	−0.72417
  	1915	0.016217	−0.11786	−0.33524
  	1916	−0.23712	−0.79448	−1.17987
  	1917	0.020851	−0.31695	−0.30797
  	1918	−0.00017	−0.20379	−0.42295
  	1919	0.003761	0.079721	0.31422
  	1920	−0.01211	−0.21388	−0.23505
  	1921	−0.23852	−0.78111	−1.15703
  	1922	−0.01943	−0.36905	−0.84702
  	1923	−0.11396	−0.29114	−1.28313
  	1924	−0.02134	−0.19369	−0.87972
  	1925	0.019202	−0.23042	−0.31619
  	1927	0.016189	0.022638	−0.210103
  	1928	−0.11288	−0.43825	−1.01888
  	1929	−0.15456	−0.55089	−1.75387
  	1930	−0.04421	−0.41059	−1.08044
  	1931	−0.02591	−0.15838	−0.64711
  	1932	−0.03919	−0.38915	−1.40276
  	1933	0.017422	0.39976	0.60926
  	1934	−0.09323	−0.42485	−1.39982
  	1935	−0.00778	−0.23173	−0.65059
  	1936	−0.04034	−0.37519	−0.84927
  	1937	−0.00128	0.221931	0.260665
  	1938	−0.02216	−0.35136	−0.76624
  	1939	−0.04121	−0.30657	−0.73842
  	1940	−0.00255	−0.03829	−0.60883
  	1941	0.001721	−0.28062	−0.72685
  	1942	−0.0357	−0.30908	−0.99946
  	1943	0.001724	0.258581	0.240667
  	1945	−0.02465	−0.27186	−0.86081
  	1946	−0.08093	−0.47696	−1.43226
  	1947	−0.03385	−0.32059	−0.3286
  	1950	0.002196	−0.17359	−0.19672
  	1951	0.006991	−0.20072	−0.25329
  	1952	−0.00608	−0.40942	−0.73578
  	1953	0.005028	−0.15884	−0.16945
  	1954	−0.01496	−0.38759	−0.80625
  	1955	−0.00401	−0.23755	−0.2686
  	1956	−0.0131	−0.35273	−0.47846
  	1957	−0.33149	−0.64113	−1.67356
  	1958	0.011706	0.158574	0.307924
  	1960	0.001843	0.620171	0.791092
  	1961	0.007272	0.209398	0.407065
  	1962	−0.03168	−0.28618	−0.39373
  	1963	−0.03105	−0.33984	−1.10317
  	1964	−0.02235	−0.19517	−0.60335
  	1966	−0.01351	−0.15096	−0.50109
  	1967	−0.0447	−0.30407	−0.77666
  	1968	0.018818	0.632814	1.006789
  	1969	−0.02596	−0.08579	−0.5593
  	1970	−0.00539	−0.12713	−0.51489
  	1971	−0.00231	−0.27674	−0.53183
  	1972	0.011694	−0.16092	−0.17151
  	1973	0.025222	0.269645	−0.254999
  	1974	0.005887	−0.23322	−0.3102
  	1975	0.010273	0.158669	0.375971
  	1976	0.01164	0.069451	0.30272
  	1977	0.003153	0.020107	0.291161
  	1978	0.010275	0.035343	0.290966
  	1979	−0.00726	0.290123	0.41272
  	1980	0.027274	0.114447	0.317692
  	1981	−0.00299	−0.18464	−0.18655
  	1982	0.003371	−0.20588	−0.27555
  	1983	−0.02234	−0.24084	−0.25563
  	1984	−0.01421	−0.27928	−0.47362
  	1985	−0.01976	−0.32802	−0.50237
  	1986	0.007511	0.140653	0.381245
  	1987	−0.07456	−0.17753	−1.53576
  	1988	−0.11518	−0.48269	−0.6296
  	1989	−0.02835	−0.34393	−0.51483
  	1992	0.025232	0.10373	0.212754
  	1993	−0.01001	0.495077	0.431265
  	1994	0.011564	0.199355	0.29528
  	1995	−0.08513	−0.34241	−0.75858
  	1996	0.009808	−0.08644	−0.66723
  	1997	−0.00362	−0.24336	−0.58573
  	1998	−0.027543	−0.140155	−0.699914
  	1999	0.010602	0.381886	0.466869
  	2000	0.005232	0.090412	0.303792
  	2001	−0.04158	−0.10036	−0.75716
  	2002	0.00709	−0.25448	−0.42862
  	2003	0.020328	0.349002	0.540023
  	2004	−0.10392	−0.26626	−1.14552
  	2005	−0.00395	−0.14092	−0.81253
  	2006	0.018924	0.16205	0.301643
  	2008	0.017035	−0.18494	−0.32494
  	2009	−0.0108	−0.2725	−0.60257
  	2010	0.062715	0.858399	1.070711
  	2011	−0.00319	−0.23151	−0.40707
  	2013	0.016426	0.585105	0.735072
  	2014	0.015113	−0.07451	−0.25615
  	2015	0.015706	0.227053	0.434043
  	2016	−0.01066	−0.06296	−0.26564
  	2017	0.029794	0.296055	0.351559
  	2018	0.029692	0.437282	0.898887
  	2019	0.021497	0.043623	0.287068
  	2020	0.012762	−0.00058	0.249706
  	2021	0.019174	0.298194	0.539625
  	2022	−0.00953	0.15747	0.378583
  	2024	0.002746	0.021635	0.240366
  	2025	−0.01867	0.148242	0.393055
  	2026	0.012409	0.29772	0.537753
  	2027	−0.10141	−0.42795	−0.96011
  	2028	−0.04498	−0.43649	−1.45709
  	2029	−0.00698	0.084208	0.226775
  	2030	−0.01906	−0.07943	−0.3736
  	2031	0.037343	0.135145	0.345018
  	2034	0.016288	0.26475	0.36449
  	2035	0.006041	−0.39239	−0.2779
  	2036	0.005805	−0.16315	−0.18766
  	2037	0.008439	−0.20905	−0.20892
  	2038	−0.04899	−0.25655	−0.65559
  	2039	0.008925	−0.17251	−0.16471
  	2041	0.025259	0.472669	0.602447
  	2042	0.003359	−0.068862	−0.130822
  	2043	−0.02582	−0.14361	−0.66288
  	2044	0.009058	0.271975	0.401515
  	2045	0.003375	0.481213	0.58199
  	2046	0.030247	0.202417	0.360615
  	2047	−0.01954	−0.24101	−0.52265
  	2048	0.02079	0.122979	0.287027
  	2049	0.01841	0.128683	0.297137
  	2050	−0.07838	−0.3133	−0.81839
  	2051	0.035655	0.12048	0.325558
  	2052	0.019567	0.208663	0.305192
  	2053	0.006616	−0.14349	−0.25109
  	2054	0.01283	0.763707	1.304963
  	2055	0.011199	0.145867	0.391723
  	2056	0.017212	−0.089889	−0.160576
  	2057	0.020607	−0.18267	−0.20839
  	2058	−0.01011	0.234598	0.4539
  	2059	0.028485	0.975327	1.038984
  	2060	−0.00122	−0.11435	−0.26342
  	2061	0.007696	−0.15684	−0.41357
  	2062	−0.10026	−0.36029	−1.4428
  	2063	−0.0135	−0.27765	−0.73306
  	2065	0.013947	0.089198	0.20872
  	2066	−0.00563	−0.28159	−0.25268
  	2067	−0.034481	−0.314757	−0.571005
  	2068	0.014892	0.234483	0.341533
  	2069	0.013673	−0.24452	−0.31746
  	2070	−0.03035	−0.24676	−0.33611
  	2071	0.016716	0.069954	0.274927
  	2072	−0.00023	−0.14279	−0.18875
  	2074	0.020103	0.397908	0.358054
  	2075	0.000883	−0.16172	−0.27555
  	2076	0.004859	0.17127	0.332493
  	2077	0.01037	−0.21565	−0.18888
  	2078	−0.01703	−0.29207	−0.3353
  	2079	0.004482	−0.13823	−0.1988
  	2080	−0.00423	0.264912	0.538955
  	2083	−0.01884	−0.22222	−0.54983
  	2084	0.002429	0.191739	0.286946
  	2086	−0.11171	−0.3468	−1.66202
  	2089	−0.00222	−0.2653	−0.22905
  	2090	−0.00873	−0.25551	−0.39288
  	2091	0.017863	0.3995	0.563314
  	2092	−0.02737	−0.29124	−0.54792
  	2093	0.001438	0.393312	0.645013
  	2094	−0.00161	0.329179	0.599467
  	2095	−0.04662	−0.4555	−1.39345
  	2096	0.00868	−0.14575	−0.16084
  	2097	−0.01069	0.438307	0.530558
  	2098	0.005224	−0.1524	−0.57137
  	2099	−0.00512	−0.23121	−0.20581
  	2100	0.01594	−0.11251	−0.15343
  	2102	−0.03821	−0.13991	−0.37379
  	2103	−0.0791	−0.56806	−0.76943
  	2105	−0.0032	0.184921	0.613022
  	2107	0.028212	0.476891	0.557632
  	2108	0.016664	−0.18764	−0.19983
  	2109	0.024344	0.270797	0.434368
  	2110	0.016946	0.26032	0.406567
  	2111	−0.03403	−0.18774	−0.47693
  	2112	−0.03586	−0.18075	−0.81904
  	2113	−0.03026	−0.30742	−0.71977
  	2114	0.047553	1.260344	1.156552
  	2115	−0.01266	−0.26929	−0.3155
  	2116	−0.09454	−0.21809	−1.42535
  	2117	−0.12163	−0.41838	−1.70565
  	2118	−0.03225	−0.24102	−0.4328
  	2119	−0.0277	−0.23099	−0.76403
  	2120	0.00625	−0.06197	−0.47991
  	2121	−0.01834	−0.27363	−0.90414
  	2122	0.011765	0.253516	0.398825
  	2123	0.00067	−0.1136	−0.48147
  	2124	0.017464	−0.20661	−0.22346
  	2125	−0.0182	−0.13711	−0.28222
  	2127	−0.042666	0.689794	0.248637
  	2128	0.002977	−0.20398	−0.24483
  	2129	−0.05143	0.803666	0.887101
  	2130	0.00574	−0.21235	−0.29382
  	2131	−0.00303	−0.18488	−0.88168
  	2132	−0.001535	0.140887	0.196882
  	2133	−0.00393	−0.06911	−0.36393
  	2134	−0.03722	0.513288	0.815222
  	2135	−0.01418	−0.07171	−0.47154
  	2136	−0.016679	0.5014	0.158751
  	2137	−0.03413	−0.34893	−1.14123
  	2138	0.021545	0.163729	0.280431
  	2139	0.001657	−0.20288	−0.32099
  	2140	−0.04362	−0.26001	−0.88714
  	2141	−0.0604	−0.3014	−1.2413
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  	3713	−0.0289	−0.19531	−0.40228
  	3714	0.011165	0.155011	0.279136
  	3715	−0.00133	0.390666	0.773649
  	3716	0.021292	0.217723	0.532074
  	3717	0.029764	0.133139	0.363509
  	3719	−0.00569	0.272222	0.395599
  	3720	0.006975	0.316981	−0.554667
  	3721	−0.00718	0.174198	0.213069
  	3722	−0.01824	−0.14028	−0.55819
  	3723	0.001449	0.433877	0.750806
  	3724	−0.06438	−0.34026	−0.90631
  	3726	0.016783	0.074532	0.32937
  	3727	−0.023638	−0.142935	−0.651747
  	3728	0.005353	0.185561	0.374248
  	3729	0.015333	0.466716	0.338765
  	3730	−0.11273	−0.34033	−0.74304
  	3731	−0.052	−0.44987	−1.00602
  	3732	0.001521	0.087123	0.219262
  	3733	−0.00774	0.297037	0.411744
  	3734	0.007834	−0.27308	−0.2795
  	3735	−0.0003	0.1427	0.284445
  	3736	−0.00304	0.247981	0.419058
  	3737	−0.05269	−0.14303	−0.9691
  	3738	0.058799	0.23747	0.50269
  	3739	−0.02901	−0.34538	−0.60565
  	3740	0.008498	0.100432	0.280781
  	3741	−0.0008	0.258263	0.455968
  	3742	−0.04584	0.066503	0.375283
  	3743	−0.03349	0.288905	0.502598
  	3744	−0.04514	−0.31129	−1.31612
  	3745	0.008607	0.236502	0.379077
  	3747	0.025051	0.654614	0.673397
  	3748	−0.00402	−0.23433	−0.60235
  	3749	−0.03559	1.065448	1.023898
  	3750	−0.02419	0.213775	0.639856
  	3751	−0.03336	−0.27007	−0.76418
  	3752	−0.0443	0.339835	0.498822
  	3753	−0.01658	0.10543	0.226121
  	3754	0.009493	0.275559	0.623179
  	3755	−0.021919	0.195442	0.379175
  	3756	0.007138	0.218329	0.357365
  	3757	−0.00525	−0.21511	−0.32728
  	3758	0.012473	0.201175	0.362596
  	3759	−0.01279	−0.2507	−0.53842
  	3760	0.025025	0.151079	0.286126
  	3761	0.013849	0.149988	0.305557
  	3762	−0.02366	−0.28636	−0.81937
  	3764	−0.01564	−0.19303	−0.26092
  	3766	−0.0078	0.33788	0.559023
  	3767	−0.14766	−0.58681	−0.8303
  	3768	−0.02365	−0.02657	−0.40423
  	3769	−0.07505	−0.45329	−0.81364
  	3770	0.014256	0.252952	0.791686
  	3771	0.000762	0.414331	0.473745
  	3772	−0.04075	−0.10969	−0.87339
  	3773	0.009132	−0.19384	−0.26354
  	3774	0.006782	0.308886	0.586722
  	3775	0.016697	−0.13758	−0.22465
  	3776	−0.00641	−0.09848	−0.32179
  	3777	−0.01008	−0.30175	−0.74848
  	3778	−0.18892	−0.16936	−0.96093
  	3779	0.015198	0.460693	0.920111
  	3780	−0.00343	0.30979	0.443498
  	3781	0.007713	−0.22269	−0.19107
  	3782	−0.00516	−0.21752	−0.43031
  	3783	0.008031	−0.275	−0.26959
  	3784	0.001544	0.152755	0.22911
  	3786	0.033983	0.314454	0.467167
  	3787	−0.00797	−0.17558	−0.34756
  	3788	−0.01013	0.252803	0.451763
  	3789	0.011368	−0.17659	−0.27607
  	3790	−0.01187	0.559225	0.865392
  	3791	0.007796	−0.11536	−0.75804
  	3794	−0.02133	−0.24973	−0.60104
  	3795	0.006022	−0.33209	−0.26862
  	3796	0.010623	0.370266	0.38694
  	3797	0.014382	−0.13074	−0.1862
  	3798	−0.00565	−0.31968	−0.72164
  	3799	−0.00825	−0.25969	−0.45754
  	3801	−0.00696	−0.08637	−0.25043
  	3802	0.017105	0.245965	0.524084
  	3803	0.012106	−0.10429	−0.39847
  	3805	0.000356	0.413256	0.478106
  	3806	0.010934	0.29635	0.386202
  	3807	0.000112	−0.09254	−0.20172
  	3808	−0.029	−0.27661	−0.49614
  	3809	0.010957	0.143925	0.427276
  	3810	0.013606	0.288317	0.384979
  	3811	0.00107	−0.14349	−0.23862
  	3813	0.015757	0.049963	0.322916
  	3814	0.012775	0.268704	0.489882
  	3815	−0.00178	−0.24858	−0.55539
  	3816	0.020478	0.328518	0.363496
  	3817	0.024418	0.191881	0.339502
  	3818	−0.01942	−0.29161	−0.28157
  	3819	0.000103	0.270294	0.325421
  	3820	−0.01143	0.488676	1.0676
  	3821	−0.00952	0.403054	0.422651
  	3822	0.009236	−0.18298	−0.28602
  	3823	−0.00386	−0.02828	−0.23222
  	3824	0.014109	0.222256	0.352421
  	3825	0.02032	0.265215	0.459123
  	3826	0.033585	0.252623	0.438713
  	3827	−0.03236	−0.26125	−0.51846
  	3828	0.034594	0.156209	0.285878
  	3829	0.020227	0.248677	0.346795
  	3830	0.014978	0.091181	0.209185
  	3831	−0.00336	−0.26565	−0.32013
  	3832	−0.01958	−0.3121	−0.42927
  	3833	0.026113	0.382008	0.532301
  	3834	0.023708	−0.1401	−0.30331
  	3835	0.005344	0.232229	0.33731
  	3837	0.015978	0.148698	0.33504
  	3838	−0.06039	−0.39414	−1.08079
  	3839	−0.05249	−0.43012	−0.97039
  	3840	0.035352	0.420428	0.634365
  	3841	0.014726	0.065969	0.296027
  	3842	0.014931	0.337795	0.48071
  	3843	0.000632	0.084208	0.363903
  	3846	−0.12428	−0.61888	−1.14868
  	3847	0.024094	0.242898	0.532951
  	3848	0.014222	−0.20545	−0.18744
  	3850	−0.0071	−0.39614	−1.31291
  	3851	0.012684	0.070752	0.274745
  	3852	0.02372	0.172396	0.342361
  	3853	0.00189	−0.145487	−0.229147
  	3854	−0.00101	−0.21912	−0.72961
  	3855	0.007222	−0.15336	−0.26965
  	3856	0.007543	−0.15408	−0.15187
  	3858	0.018762	−0.28212	−0.40115
  	3859	−0.08983	−0.08099	−0.96191
  	3860	0.004134	0.11989	0.775235
  	3861	−0.00476	0.799769	0.775464
  	3862	−0.02069	0.619347	0.552404
  	3863	0.023825	0.198966	0.288914
  	3864	0.002065	−0.18112	−0.3627
  	3865	0.023799	0.373823	0.502792
  	3866	−0.07514	−0.16355	−1.15587
  	3867	−0.02357	0.426881	0.768005
  	3868	−0.06742	−0.22372	−1.48362
  	3869	0.007952	−0.20656	−0.18147
  	3870	−0.00995	−0.18825	−0.32561
  	3871	−0.09391	−0.49811	−0.67155
  	3872	−0.01577	−0.30748	−0.36469
  	3873	0.00135	−0.177	−0.26574
  	3874	0.01437	−0.27493	−0.64992
  	3875	0.008601	0.175417	0.368725
  	3877	0.0215	0.239552	0.543968
  	3878	0.007867	−0.14612	−0.219
  	3879	−0.02127	−0.13431	−0.5214
  	3881	−0.01449	−0.22729	−0.38659
  	3882	−0.008	−0.28045	−0.35033
  	3883	−0.00282	−0.22456	−0.3246
  	3884	−0.01006	0.125335	0.437432
  	3885	−0.0341	−0.33793	−0.64981
  	3886	−0.02831	−0.22518	−0.44843
  	3887	−0.00342	−0.15249	−0.46289
  	3888	0.014393	0.484554	0.495931
  	3889	0.001776	0.262078	0.383028
  	3890	0.011023	−0.01062	−0.44164
  	3892	0.004332	−0.00059	−0.38242
  	3893	0.001464	−0.14286	−0.18126
  	3894	−0.01231	−0.2316	−0.32005
  	3895	0.018186	0.089257	0.210466
  	3896	0.0075	−0.17357	−0.27499
  	3897	−0.00568	−0.14148	−0.37829
  	3898	0.002511	−0.14907	−0.15297
  	3899	−0.0092	−0.1654	−0.41466
  	3900	0.01744	0.108167	0.303529
  	3902	−0.21525	−0.62727	−0.88264
  	3903	0.012294	0.101754	0.422339
  	3904	0.007328	−0.12993	−0.17647
  	3906	0.032547	0.2237	0.374842
  	3907	0.020824	0.455249	0.666732
  	3908	0.001958	−0.08941	−0.20901
  	3909	−0.03403	−0.28041	−0.66761
  	3910	0.005124	0.373303	0.456396
  	3911	0.007527	0.436713	0.635286
  	3912	−0.01004	−0.18805	−0.1945
  	3913	−0.13841	0.130768	−0.78612
  	3914	0.005593	−0.24982	−0.45921
  	3916	0.007871	0.294561	0.472056
  	3917	0.000456	0.350453	0.512085
  	3918	−0.00721	−0.20685	−0.30782
  	3919	0.00249	0.4553	0.467418
  	3920	0.003433	0.234106	0.347743
  	3921	0.02159	0.267666	0.272491
  	3922	−0.01034	−0.23596	−0.40316
  	3923	−0.0218	−0.17331	−0.31503
  	3924	−0.01052	−0.2608	−0.45258
  	3926	0.005481	−0.19415	−0.38862
  	3927	−0.00198	−0.15223	−0.26378
  	3928	−0.00481	−0.19212	−0.60011
  	3929	−0.02907	−0.31237	−0.67115
  	3930	0.018932	0.502499	0.630779
  	3931	0.007823	0.330178	0.374828
  	3932	−0.00625	−0.19177	−0.36188
  	3934	−0.01138	−0.16719	−0.62327
  	3936	0.013418	−0.12059	−0.21994
  	3937	−0.00602	−0.17249	−0.19886
  	3938	−0.00093	−0.18338	−0.21621
  	3940	−0.0063	0.32237	0.447277
  	3941	−0.03123	0.753525	1.028617
  	3942	−0.03893	−0.15886	−1.03693
  	3943	0.016177	0.318878	0.500708
  	3944	0.029472	−0.14649	−0.37317
  	3945	−0.15185	−0.49868	−0.607
  	3946	−0.09644	−0.46037	−0.57596
  	3948	0.010157	0.279247	0.48872
  	3949	0.002141	−0.34666	−0.2661
  	3950	−0.03206	−0.28804	−0.36911
  	3951	0.006273	0.122116	0.414685
  	3952	−0.04024	0.176953	0.383377
  	3953	0.0072	−0.23691	−0.34253
  	3954	0.012744	−0.16741	−0.24655
  	3955	−0.019735	−0.159647	−0.33003
  	3957	−0.00172	0.066009	0.290683
  	3958	0.000007	0.258618	0.366426
  	3959	−0.07307	−0.35372	−0.42584
  	3960	−0.005	−0.29445	−0.89736
  	3962	−0.00971	−0.14007	−0.77128
  	3963	−0.0012	−0.19036	−0.18134
  	3964	−0.00871	−0.31654	−0.73351
  	3965	0.007545	−0.19764	−0.31117
  	3967	−0.09077	−0.42429	−0.50192
  	3968	0.002684	−0.24249	−0.27393

• TABLE 1b
  phase reporter genes

  	SEQ ID NO	log(ratio) CP	log(ratio) AP	log(ratio) BC

  	56	−0.01844	−0.2843	−0.52572
  	65	−0.043	−0.27935	−0.61442
  	70	−0.02677	0.321263	0.479287
  	177	−0.02343	−0.25951	−0.53988
  	190	−0.04631	−0.22027	−0.61104
  	199	−0.19435	−0.66091	−1.74771
  	1758	−0.0427	−0.06237	−0.68566
  	1773	0.032164	0.295407	0.487261
  	1774	0.02296	0.304684	0.561645
  	1786	0.014041	0.225619	0.584752
  	1815	0.035253	0.254518	0.53063
  	1823	0.014591	0.300107	0.456781
  	3925	−0.04398	−0.3128	−0.99975
  	3933	−0.0347	−0.12523	−0.74375
  	3947	−0.04231	−0.53589	−1.45253
  	3956	−0.00856	−0.16684	−0.95119

• Tables 2a and 2b list a set of 386 progression genes identified by searching for phase reporter genes after removing CD34 content (p<10⁻⁸) (the “progression geneset”). The CD34 content is removed by subtracting the expression level of each gene in a sample of CD34+ cells from the expression level of the gene in a tumor sample from a CML patient. The progression genes are identified by their SEQ ID NOs in Tables 2a and 2b. Information for these genes is presented in Table 8. Table 2a lists progression genes that were not disclosed in U.S.Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 2b lists progression genes that were also identified in U.S.Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Tables 2a and 2b also listed for each gene the log ratio of CD34+(−) expression level of the gene (i.e., the expression level of the gene in a tumor sample from a CML patient minus the expression level of the gene in a sample of CD34+ cells) in samples from patients of a particular phase (e.g., CP, AP, or BC) versus CD34+(−) expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase.

• TABLE 2a
  progression genes

  	SEQ ID NO	log(ratio) CP	log(ratio) AP	log(ratio) BC

  	2	−0.013036	0.331191	0.13619
  	22	−0.027625	0.25124	0.297168
  	44	−0.008283	−0.175784	−0.35176
  	74	−0.018621	0.110352	−0.541362
  	75	0.012898	−0.15485	−0.081578
  	98	−0.0065	0.226199	0.384576
  	118	0.0235	0.413795	0.572899
  	120	−0.068801	−0.238346	−0.788486
  	123	−0.014776	0.153884	0.315337
  	127	0.014361	0.2732	0.196317
  	146	−0.062898	−0.026859	−0.467529
  	166	−0.008117	−0.02223	−0.588809
  	192	−0.03375	−0.376045	−0.824014
  	201	−0.046038	0.745451	0.938831
  	252	−0.011159	−0.181168	−0.338022
  	260	−0.014983	0.169381	0.378207
  	261	0.002136	−0.013939	0.252784
  	277	−0.059071	0.153895	−0.707755
  	282	−0.011292	0.246831	0.217263
  	300	−0.015553	0.264616	0.213715
  	312	−0.006268	−0.169392	−0.415121
  	321	0.017293	0.264073	0.351815
  	329	0.015519	−0.110525	−0.132442
  	348	0.003377	0.292866	0.385025
  	359	0.011735	−0.238758	−0.159133
  	361	0.0199	−0.29195	−0.308127
  	369	0.015105	−0.30705	−0.467622
  	379	0.011972	0.153175	0.287232
  	382	−0.034613	0.539856	0.385649
  	392	−0.018091	0.211741	0.151359
  	397	0.001911	−0.204817	−0.142157
  	398	−0.055256	0.454774	0.463563
  	401	0.010902	−0.0223	−0.435077
  	407	0.022957	−0.146156	−0.144178
  	408	0.000587	0.042633	0.171636
  	413	−0.004104	−0.021944	−0.541188
  	432	−0.021105	0.318234	0.36938
  	453	0.000187	−0.016503	−0.233794
  	462	0.015733	−0.049378	−0.203749
  	464	−0.007901	−0.242419	−0.192786
  	468	−0.069818	0.055712	−0.792861
  	483	0.022087	0.013675	−0.264371
  	487	−0.044506	−0.226859	−0.730255
  	490	0.032225	0.697253	0.473438
  	493	0.005365	0.117615	0.279824
  	506	0.002222	0.244418	0.413136
  	508	−0.001048	0.149848	0.252886
  	513	−0.025942	0.105185	−0.589267
  	532	0.013898	−0.091144	−0.105794
  	535	−0.02973	0.31094	−0.640132
  	549	−0.024057	−0.192808	−0.507538
  	562	−0.007465	−0.085295	−0.451408
  	564	0.010706	0.16159	0.377863
  	565	−0.013377	0.189935	0.358398
  	596	−0.027369	−0.300983	−0.676728
  	602	−0.02947	0.152602	0.288592
  	607	−0.03208	0.163679	0.433561
  	629	−0.017135	0.164754	0.393246
  	631	−0.005919	0.029702	0.182895
  	638	0.005995	0.158171	0.295784
  	641	−0.002351	0.141381	−0.371398
  	644	0.011035	−0.188829	−0.236191
  	648	−0.000305	0.09399	0.156447
  	671	−0.052686	0.224817	−0.778464
  	678	−0.011662	−0.03032	−0.483853
  	686	−0.044146	0.393448	0.352519
  	687	0.004128	0.014188	0.147004
  	688	−0.007112	0.135577	−0.384238
  	692	0.01078	−0.193913	−0.339249
  	694	0.026903	0.238728	0.198984
  	699	0.002836	−0.136336	−0.204499
  	700	−0.003573	0.186663	0.111998
  	702	−0.004795	0.43693	0.231795
  	704	0.008652	0.448527	0.623811
  	708	0.035423	−0.072534	−0.243577
  	710	0.00051	−0.260385	−0.325256
  	715	−0.031368	−0.034762	−0.28179
  	725	0.018721	−0.110491	−0.07631
  	727	0.011701	0.352484	0.599663
  	730	0.007214	−0.100867	−0.390067
  	739	−0.021549	0.313399	0.230556
  	758	0.006066	0.197232	0.154028
  	774	−0.011428	0.297906	0.460758
  	781	0.049464	0.661373	0.621414
  	789	−0.011135	0.073025	0.220549
  	794	0.00587	−0.124811	−0.092198
  	852	−0.009777	0.061913	0.217413
  	862	0.012512	0.101103	0.346959
  	878	−0.007159	0.624676	0.342539
  	879	0.015292	0.310113	−0.619546
  	902	0.01057	0.108517	0.282889
  	906	0.009153	0.106628	0.432846
  	912	−0.03355	−0.086456	−0.556116
  	913	−0.002153	−0.162393	−0.176945
  	934	−0.001515	0.49437	0.349162
  	949	−0.009006	−0.003959	−0.260665
  	969	0.009521	−0.194416	−0.088755
  	983	−0.009189	−0.179037	−0.279808
  	984	0.003783	0.428077	−0.304577
  	995	0.018194	0.115536	0.453015
  	1005	−0.004206	0.264613	0.406912
  	1006	0.013715	0.253173	−0.48171
  	1014	−0.027032	0.218431	0.369874
  	1027	−0.097802	0.14838	−0.409138
  	1030	0.012193	−0.156904	−0.129918
  	1036	0.018457	0.150121	0.282032
  	1042	0.016406	0.12399	0.254155
  	1047	−0.010956	0.160388	0.293704
  	1053	−0.003597	0.168234	0.188554
  	1065	0.041337	0.356808	0.457428
  	1086	0.012167	0.126556	0.308808
  	1089	−0.056921	0.265345	0.488138
  	1092	0.031164	0.741399	0.650443
  	1093	−0.019458	0.265262	0.281598
  	1100	−0.026376	−0.107488	0.120579
  	1105	0.000402	0.241675	0.374547
  	1106	0.013275	0.053145	0.284804
  	1111	0.006695	0.390109	0.467033
  	1113	0.00931	−0.151037	−0.094238
  	1145	−0.003373	−0.121256	−0.288823
  	1161	−0.036419	−0.112814	−0.289979
  	1169	0.004364	−0.149179	−0.137703
  	1180	−0.003015	0.149485	0.243152
  	1181	−0.006552	0.354743	0.273738
  	1182	−0.063925	0.133911	−0.796733
  	1201	−0.024631	0.061529	−0.462534
  	1211	−0.0131	0.42541	0.389219
  	1227	0.003709	−0.172158	−0.119982
  	1228	−0.001968	−0.182794	−0.15988
  	1234	0.003295	−0.168464	−0.233929
  	1264	0.007382	−0.120962	−0.228059
  	1288	−0.025178	0.393585	0.566352
  	1294	0.004545	0.126708	0.283647
  	1308	−0.051939	−0.225136	−1.142094
  	1324	0.000802	0.195216	0.368476
  	1327	0.0232	0.29162	0.330751
  	1328	0.016117	−0.125314	−0.193334
  	1333	−0.001615	0.157104	0.160918
  	1334	−0.003194	0.078374	−0.585411
  	1352	−0.013243	−0.259131	−0.724495
  	1364	0.020286	−0.059623	−0.36669
  	1394	−0.038031	0.569499	0.281012
  	1400	−0.034692	−0.392913	−0.855372
  	1408	0.012613	0.202286	−0.410509
  	1421	0.015803	0.301704	−0.280571
  	1434	0.023441	0.24849	0.404885
  	1465	0.011301	1.119758	0.380817
  	1475	0.002495	−0.174538	−0.144746
  	1489	−0.005825	0.171399	0.198891
  	1503	−0.010846	0.33961	0.344346
  	1538	0.008774	0.250497	0.380736
  	1544	−0.001566	−0.118486	−0.225612
  	1565	0.003841	−0.24087	−0.188087
  	1586	−0.05968	0.131214	0.231979
  	1596	−0.012267	0.315077	0.462982
  	1598	−0.040336	0.405119	0.295977
  	1600	0.016473	0.171937	0.480309
  	1613	0.018672	0.639835	0.686131
  	1615	0.003796	−0.155045	−0.123787
  	1621	0.000743	0.182262	0.22026
  	1622	−0.01422	0.108504	0.441113
  	1624	−0.003494	−0.128858	−0.416283
  	1631	−0.066238	0.08156	0.35517
  	1644	0.012751	0.004567	−0.256495
  	1653	−0.051037	0.575903	0.659891
  	1666	−0.005018	0.304418	0.391773
  	1667	0.020618	−0.152906	−0.073514
  	1674	0.001052	0.230389	0.365551
  	1707	−0.10203	−0.508005	−0.433948
  	1713	−0.000033	0.227119	0.293211
  	1723	−0.008555	−0.013157	0.311742
  	1726	0.01878	−0.134004	−0.114544
  	1729	0.017853	0.122885	0.403719
  	1740	0.000129	0.082648	0.202706
  	1744	−0.008165	0.028902	0.157605
  	1754	−0.03329	0.24969	0.276391
  	1756	−0.006572	−0.090777	−0.187299
  	1764	−0.023292	0.061919	0.439367
  	1765	−0.069608	0.229406	−0.942888
  	1769	0.004735	0.111816	0.380203
  	1772	−0.053231	0.914364	0.703125
  	1784	0.011665	0.266176	0.262102
  	1798	0.006863	0.125618	0.179833
  	1802	−0.006187	−0.271892	−0.547214
  	1813	0.004929	0.074195	−0.38902
  	1822	0.008709	0.058535	0.172787
  	1851	−0.038706	0.176417	−0.585557
  	1854	0.011347	−0.148867	−0.08759
  	1856	0.023502	−0.039695	−0.260378
  	1857	0.001175	−0.00306	−0.260983
  	1864	−0.023131	−0.110894	−0.595764
  	1902	0.011275	−0.14224	−0.083923
  	1906	−0.018987	−0.066969	−0.26783
  	1910	−0.014553	−0.104128	−0.202699
  	1927	0.016189	0.022638	−0.210103
  	1936	−0.008747	−0.190402	−0.17087
  	1966	0.009815	−0.207021	−0.109949
  	1973	0.025222	0.269645	−0.254999
  	1997	0.000408	−0.206852	−0.093692
  	1998	−0.027543	−0.140155	−0.699914
  	2024	0.002746	0.021635	0.240366
  	2041	−0.006546	0.162101	0.390622
  	2042	0.003359	−0.068862	−0.130822
  	2054	0.003287	0.188219	0.311283
  	2056	0.017212	−0.089889	−0.160576
  	2059	−0.020181	1.117376	0.593213
  	2067	−0.034481	−0.314757	−0.571005
  	2069	0.020052	−0.126164	−0.092528
  	2084	−0.030024	0.35537	0.651561
  	2116	0.013573	−0.038963	−0.25063
  	2121	−0.071015	0.041386	−0.850915
  	2127	−0.042666	0.689794	0.248637
  	2132	−0.001535	0.140887	0.196882
  	2136	−0.016679	0.5014	0.158751
  	2148	0.007504	−0.089503	−0.424451
  	2162	−0.018781	−0.151041	−0.25681
  	2196	0.001252	−0.045446	−0.145241
  	2197	0.011939	0.082814	0.421803
  	2211	0.016656	−0.118424	−0.17814
  	2218	−0.001994	0.132273	0.102983
  	2222	−0.080043	0.129091	0.187538
  	2247	0.014934	−0.139989	−0.120912
  	2248	−0.012664	0.324801	0.485921
  	2259	0.009135	0.109045	−0.390417
  	2276	0.010096	−0.162022	−0.120129
  	2277	0.013334	0.571954	−0.227756
  	2282	0.003573	−0.28411	−0.296893
  	2286	−0.00426	−0.361198	−0.342302
  	2298	−0.042053	−0.27671	−0.589169
  	2302	0.008627	−0.135924	−0.184813
  	2310	−0.001488	−0.154965	−0.151611
  	2334	0.022782	0.118742	0.155021
  	2344	−0.046131	−0.043556	0.354686
  	2373	0.013698	0.020747	−0.300319
  	2388	−0.057599	0.240909	0.4755
  	2392	0.007643	−0.159192	−0.126831
  	2398	−0.04217	0.124478	−0.490219
  	2414	0.006247	0.039279	0.231344
  	2458	−0.047592	−0.021181	0.62265
  	2464	0.009492	0.497028	0.550105
  	2465	−0.061732	0.844778	0.746645
  	2474	−0.010535	0.317139	0.32638
  	2479	0.009625	−0.032207	−0.206553
  	2482	0.007713	0.134365	0.22816
  	2486	0.008277	−0.165135	−0.505359
  	2494	−0.008876	−0.013903	−0.345788
  	2495	0.023159	−0.11675	−0.103801
  	2501	0.024313	−0.133841	−0.10317
  	2517	0.010041	−0.026346	−0.284518
  	2541	0.001637	−0.123709	−0.165061
  	2555	0.009862	−0.295888	−0.195271
  	2561	0.003441	0.143297	0.393623
  	2563	−0.001684	−0.157035	−0.180935
  	2567	0.018774	0.481516	0.617251
  	2580	0.001717	0.072093	0.449871
  	2584	−0.108511	0.237285	0.358945
  	2591	−0.014377	0.016583	0.170925
  	2599	−0.004314	0.138559	−0.449886
  	2603	0.011638	−0.148946	−0.141157
  	2606	−0.008722	−0.002843	−0.263652
  	2612	0.006823	−0.083968	−0.181774
  	2627	0.033377	−0.002066	−0.307558
  	2631	−0.091338	−0.170022	−1.015137
  	2637	0.000709	−0.02223	−0.36686
  	2654	−0.018035	−0.080645	−0.380195
  	2659	0.022976	0.537017	0.816212
  	2664	−0.002476	−0.035144	−0.354387
  	2696	0.061699	0.295673	0.624181
  	2698	−0.008783	−0.162188	−0.319096
  	2699	0.021373	−0.029099	−0.143444
  	2700	0.004112	0.278744	0.204271
  	2707	0.014731	−0.005959	−0.192094
  	2750	0.007282	−0.224306	−0.335665
  	2769	−0.085357	0.275787	−0.772084
  	2772	0.017216	−0.120145	−0.343286
  	2775	−0.011673	0.769212	0.451896
  	2810	0.004075	−0.190069	−0.240619
  	2811	0.009903	−0.176453	−0.085968
  	2813	0.003336	0.202659	0.191714
  	2815	0.006303	0.092394	0.150836
  	2824	0.00192	−0.131874	−0.166371
  	2835	0.020297	−0.126422	−0.206971
  	2856	0.006157	−0.130875	−0.287515
  	2864	−0.012584	0.112957	0.202569
  	2865	0.002638	−0.150304	−0.265439
  	2868	−0.002354	0.025594	0.276877
  	2873	−0.003375	−0.040933	−0.559433
  	2891	0.012968	0.26685	0.212612
  	2897	−0.004267	0.32308	0.463093
  	2905	−0.045096	−0.397135	−0.859917
  	2926	−0.005235	0.098392	0.200836
  	2931	0.024967	0.193228	0.410268
  	2936	0.024484	−0.182182	−0.112346
  	2938	0.01805	−0.289863	−0.273244
  	2946	0.005996	−0.125692	−0.084214
  	2964	0.019559	−0.127505	−0.385534
  	2965	0.007544	−0.131222	−0.15763
  	2972	−0.062089	0.082359	0.199472
  	2973	0.003145	0.146062	0.413226
  	2976	0.007741	0.072786	−0.299474
  	2981	−0.018057	−0.15181	−0.335472
  	2995	0.012536	−0.169059	−0.090252
  	3004	−0.004586	0.054952	0.213188
  	3014	0.005466	−0.153481	−0.203641
  	3022	0.015475	−0.112142	−0.208532
  	3059	−0.014859	0.269937	0.241767
  	3079	−0.011007	−0.20423	−0.516356
  	3085	−0.007467	−0.154645	−0.263535
  	3094	0.009534	−0.137767	−0.14642
  	3105	0.023282	0.325101	0.254346
  	3120	0.0307	0.350781	−0.241198
  	3130	0.009997	−0.13136	−0.143976
  	3132	0.011847	−0.085343	−0.251605
  	3161	0.008344	−0.156984	−0.187369
  	3185	−0.011662	0.324166	0.476811
  	3194	0.002083	0.14088	0.284904
  	3211	0.004157	0.206272	0.386628
  	3214	0.025459	0.102741	0.240957
  	3215	0.00353	−0.064073	−0.167793
  	3228	0.017223	−0.161965	−0.0726
  	3237	0.002668	−0.009235	0.21907
  	3245	−0.039738	−0.344767	−0.512409
  	3269	−0.033522	−0.404287	−0.588228
  	3279	−0.059744	0.264262	0.389371
  	3288	−0.001709	−0.176379	−0.380142
  	3328	−0.001545	0.072595	0.2077
  	3337	0.01359	0.244776	0.208125
  	3338	−0.020347	−0.138845	−0.506552
  	3341	−0.049209	−0.011969	−0.419139
  	3356	0.023516	−0.13485	−0.110476
  	3357	0.000456	−0.135074	−0.091856
  	3380	−0.012204	−0.399725	−0.454969
  	3387	0.008267	0.330665	0.191095
  	3390	−0.002049	0.248303	0.32703
  	3395	−0.006382	−0.249059	−0.201365
  	3402	−0.084896	0.054938	0.463716
  	3416	−0.039529	−0.201668	−0.578439
  	3420	−0.000395	−0.09677	−0.20635
  	3423	0.012558	0.087882	0.242394
  	3426	0.01107	0.146821	−0.432986
  	3443	−0.015748	−0.058532	−0.400899
  	3444	−0.017838	0.112361	0.21707
  	3470	0.01235	0.202663	0.425686
  	3473	0.007791	0.222727	0.486992
  	3477	−0.007804	−0.012007	0.180183
  	3496	−0.078914	0.88838	0.619244
  	3516	−0.03045	−0.252169	−0.485051
  	3522	0.014247	0.255693	0.387975
  	3549	0.012122	1.072368	0.652041
  	3560	0.010452	0.067171	0.167825
  	3569	0.008055	0.236448	0.463364
  	3571	0.012994	−0.148049	−0.087744
  	3579	0.004924	−0.17069	−0.122234
  	3585	−0.001411	0.203954	0.124424
  	3594	0.022686	−0.159764	−0.113605
  	3595	0.00889	0.778268	0.724542
  	3627	−0.018961	−0.122255	−0.455286
  	3649	−0.00753	−0.075377	−0.245985
  	3655	−0.009543	−0.030372	0.280245
  	3658	0.010488	−0.100563	−0.316822
  	3662	−0.021261	−0.177479	−0.164925
  	3678	−0.018901	−0.069804	−0.40405
  	3689	0.008179	0.111666	0.212243
  	3715	0.000597	0.19448	0.237315
  	3720	0.006975	0.316981	−0.554667
  	3724	−0.006756	0.02331	−0.392742
  	3727	−0.023638	−0.142935	−0.651747
  	3749	0.01003	0.043979	0.215776
  	3751	0.029168	−0.073576	−0.140182
  	3754	0.001496	0.107186	0.165913
  	3755	−0.021919	0.195442	0.379175
  	3774	0.008601	0.081842	0.189429
  	3781	−0.027603	−0.124679	−0.389211
  	3795	−0.009508	−0.235417	−0.340756
  	3848	0.008156	−0.137025	−0.091425
  	3853	0.00189	−0.145487	−0.229147
  	3854	−0.009932	−0.323309	−0.627916
  	3865	−0.006782	0.081835	0.099887
  	3869	0.026028	−0.164373	−0.08952
  	3874	0.002977	0.004837	−0.354182
  	3878	−0.00536	−0.135863	−0.293698
  	3908	0.01371	−0.080601	−0.140019
  	3938	0.005563	−0.114606	−0.098469
  	3941	0.018012	0.177639	0.090444
  	3955	−0.019735	−0.159647	−0.33003

• TABLE 2b
  progression genes

  	SEQ ID NO	log(ratio) CP	log(ratio) AP	log(ratio) BC
  	3925	0.003797	−0.153433	−0.114664

• Table 3 lists the “top ten” genes that are associated with progression and response, independent of normal CD34+ expression, based onlog 10 ratio of expression compared to the chronic phase pool. These genes are identified by their SEQ ID NOs in Table 3. Information for these genes is presented in Table 8.

• TABLE 3
  “top ten” genes

  SEQ
  ID NO	log(ratio) CP	log(ratio) AP	log(ratio) BC	REGULATION

  902	0	0	0.599663	up
  984	0	0	−0.77846	down
  1334	0	0	−0.94289	down
  1756	0	0	−0.78849	down
  1813	0	0	−0.85091	down
  1973	0	0	−0.79673	down
  2056	0	0	−1.01514	down
  2211	0	0	−0.82401	down
  2561	0	0	0.686131	up
  2810	0	0	−0.85992	down
  2813	0	0	0.652041	up
  2815	0	0	0.816212	up
  2824	0	0	−1.14209	down
  2864	0	0	0.651561	up
  2973	0	0	0.746645	up
  3085	0	0	−0.85537	down
  3211	0	0	0.617251	up
  3477	0	0	0.619244	up
  3749	0	0	0.703125	up
  3941	0	0	0.659891	up

• Table 4 lists a set of 228 genes associated with imatinib resistance (the “imatinib resistance genes”). The imatinib resistance genes are identified by their SEQ ID NOs in Table 4. Information for these genes is presented in Table 8. Table 4 also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) or IM resistance (IM) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase or IM resistance.

• TABLE 4
  genes associated with imatinib resistance

  SEQ ID NO	log(ratio) CP	log(ratio) AP	log(ratio) BC	log(ratio)IM

  20	0	0	−0.38709	0.263887
  28	0	0	−0.01912	0.265124
  50	0	0	0.04967	0.383703
  72	0	0	−0.03184	0.248668
  77	0	0	−0.1097	0.230979
  91	0	0	−0.21363	0.302135
  93	0	0	0.012872	0.248989
  97	0	0	0.084015	0.441542
  124	0	0	0.230888	0.535462
  134	0	0	−0.03703	0.179006
  150	0	0	−0.0693	0.172068
  155	0	0	−0.13679	0.157108
  171	0	0	0.196959	0.633551
  195	0	0	0.02123	0.207227
  243	0	0	0.11112	0.695707
  254	0	0	−0.08112	0.269401
  269	0	0	−0.03573	0.298949
  275	0	0	−0.15251	0.212305
  283	0	0	−0.03596	0.21647
  292	0	0	0.20614	0.549719
  342	0	0	0.208194	0.677793
  371	0	0	−0.06027	0.449786
  372	0	0	−0.02106	0.351234
  377	0	0	−0.16901	0.161438
  386	0	0	−0.07531	0.180776
  406	0	0	−0.06767	0.371699
  426	0	0	−0.05036	0.281576
  442	0	0	−0.14473	0.198718
  456	0	0	−0.05428	0.215394
  459	0	0	−0.03202	0.345771
  469	0	0	−0.18903	0.227286
  480	0	0	0.038217	0.684655
  531	0	0	−0.17195	0.414879
  568	0	0	−0.06414	0.098452
  622	0	0	−0.40798	0.833497
  662	0	0	−0.00884	0.217496
  663	0	0	−0.09438	0.107198
  670	0	0	−0.17245	0.1338
  709	0	0	0.187456	0.553818
  722	0	0	−0.11073	0.162124
  768	0	0	−0.10115	0.42413
  785	0	0	0.219511	0.690758
  796	0	0	−0.12656	0.145981
  856	0	0	−0.01924	0.400575
  880	0	0	−0.10236	0.278475
  894	0	0	−0.02732	0.206984
  917	0	0	−0.25561	0.212912
  924	0	0	0.224269	0.708077
  973	0	0	−0.01275	0.730765
  977	0	0	−0.10317	0.400818
  980	0	0	−0.1785	0.286644
  1008	0	0	−0.10928	0.108172
  1014	0	0	0.148244	0.865065
  1023	0	0	0.098335	0.878985
  1037	0	0	−0.33476	0.837053
  1038	0	0	−0.20627	0.621468
  1052	0	0	−0.2069	0.236861
  1059	0	0	0.148036	0.402311
  1074	0	0	−0.33264	0.239842
  1089	0	0	0.174284	0.985452
  1095	0	0	0.304656	0.927005
  1124	0	0	−0.07093	0.616113
  1143	0	0	−0.18175	0.201291
  1157	0	0	−0.18174	0.21747
  1170	0	0	−0.08377	0.431166
  1173	0	0	−0.09515	0.560044
  1182	0	0	−0.45446	0.142546
  1190	0	0	0.041007	0.359776
  1215	0	0	−0.06781	0.83596
  1219	0	0	−0.07224	0.165806
  1224	0	0	−0.05776	0.205308
  1247	0	0	−0.08694	0.185421
  1249	0	0	0.263515	0.605748
  1267	0	0	0.263464	1.063745
  1323	0	0	−0.2206	0.10102
  1329	0	0	−0.00537	0.436924
  1331	0	0	−0.01409	0.755256
  1336	0	0	−0.15667	0.34331
  1367	0	0	−0.3207	0.489696
  1379	0	0	−0.17026	0.205201
  1389	0	0	0.079937	0.359209
  1435	0	0	0.092179	0.722108
  1449	0	0	−0.467	0.171956
  1451	0	0	0.425181	0.859676
  1478	0	0	−0.152	0.122073
  1482	0	0	0.111952	0.395553
  1494	0	0	−0.16752	0.177726
  1526	0	0	−0.15569	0.166092
  1534	0	0	0.10057	0.802351
  1549	0	0	−0.01958	0.262207
  1566	0	0	−0.07228	0.314048
  1591	0	0	0.253125	0.761339
  1657	0	0	−0.02703	0.334287
  1671	0	0	−0.13532	0.128801
  1708	0	0	−0.03956	0.206351
  1709	0	0	0.265264	0.510844
  1731	0	0	−0.16089	0.119466
  1789	0	0	−0.28125	0.246382
  1820	0	0	−0.42872	0.604742
  1839	0	0	−0.01985	0.652489
  1840	0	0	0.057241	0.774482
  1898	0	0	−0.39467	0.378527
  1948	0	0	0.082745	0.793455
  1949	0	0	−0.18208	0.868135
  1959	0	0	−0.22455	0.344545
  1965	0	0	−0.26522	0.569866
  2012	0	0	−0.35247	0.31479
  2033	0	0	0.040006	0.345342
  2073	0	0	0.039277	0.877752
  2081	0	0	−0.05539	0.149592
  2087	0	0	−0.29516	0.404949
  2088	0	0	−0.02581	0.326797
  2106	0	0	−0.23592	0.332507
  2126	0	0	−0.02439	0.515267
  2145	0	0	−0.2559	0.725553
  2151	0	0	−0.01135	0.414351
  2172	0	0	−0.08199	0.39351
  2178	0	0	−0.26619	0.102312
  2181	0	0	−0.06055	0.158135
  2183	0	0	0.223605	0.977949
  2189	0	0	0.216936	1.068883
  2199	0	0	−0.27714	0.840265
  2207	0	0	−0.29681	0.440807
  2228	0	0	−0.05689	0.930733
  2244	0	0	−0.37335	0.576383
  2269	0	0	−0.17482	0.171115
  2285	0	0	−0.05323	0.923962
  2286	0	0	−0.11188	0.142335
  2289	0	0	−0.31747	0.354229
  2292	0	0	0.437319	0.959855
  2354	0	0	−0.06186	0.222863
  2387	0	0	−0.60522	0.324344
  2388	0	0	−0.11786	0.725499
  2408	0	0	0.27178	0.449011
  2427	0	0	−0.0812	0.174195
  2437	0	0	0.027895	1.082811
  2449	0	0	0.012028	0.297163
  2479	0	0	−0.22582	0.179989
  2492	0	0	−0.25009	0.349156
  2531	0	0	0.07276	0.662312
  2545	0	0	0.021603	0.945236
  2553	0	0	−0.01276	0.395767
  2564	0	0	−0.28345	0.250146
  2568	0	0	−0.10977	0.19616
  2582	0	0	0.253015	0.634172
  2615	0	0	0.128864	1.013705
  2618	0	0	−0.2905	0.559533
  2629	0	0	−0.06243	0.410775
  2633	0	0	−0.41692	0.392893
  2652	0	0	0.205031	0.647252
  2653	0	0	−0.00396	0.377357
  2660	0	0	−0.53433	0.393617
  2665	0	0	0.062554	0.686441
  2666	0	0	0.017231	0.276612
  2686	0	0	0.074055	0.352962
  2697	0	0	0.142879	0.722647
  2756	0	0	0.033883	0.281303
  2780	0	0	−0.43199	0.457222
  2802	0	0	0.032077	0.248953
  2807	0	0	0.088818	0.865409
  2828	0	0	0.375805	0.936957
  2844	0	0	−0.10182	0.193285
  2879	0	0	−0.11063	0.376181
  2896	0	0	−0.12602	0.433851
  2942	0	0	0.038329	0.261638
  2955	0	0	0.337985	0.616413
  2977	0	0	0.006318	0.640784
  2980	0	0	−0.06256	0.752042
  2984	0	0	−0.0839	0.535325
  2989	0	0	−0.04767	0.23291
  2994	0	0	−0.12413	0.24541
  3004	0	0	−0.22221	0.402371
  3015	0	0	−0.38468	0.767185
  3040	0	0	−0.15874	0.553807
  3051	0	0	−0.16014	0.258388
  3095	0	0	−0.23449	0.453399
  3145	0	0	0.046709	0.349592
  3149	0	0	−0.07479	0.13184
  3172	0	0	−0.09216	0.235379
  3178	0	0	−0.16051	0.189495
  3181	0	0	−0.18123	0.657828
  3183	0	0	−0.08563	0.644291
  3234	0	0	−0.09319	0.622993
  3239	0	0	−0.15225	0.543178
  3263	0	0	−0.09885	0.51508
  3267	0	0	−0.0802	0.247087
  3272	0	0	−0.06519	0.20193
  3284	0	0	−0.39928	0.564677
  3317	0	0	0.042257	0.663222
  3324	0	0	−0.0387	0.202691
  3334	0	0	−0.14218	0.402162
  3342	0	0	0.094368	0.377785
  3360	0	0	−0.18153	0.352019
  3370	0	0	−0.07291	0.154629
  3373	0	0	0.266208	1.01143
  3378	0	0	0.154822	0.471737
  3389	0	0	0.096215	0.292396
  3402	0	0	0.166222	0.929501
  3433	0	0	−0.08958	0.164089
  3476	0	0	−0.02612	0.185903
  3479	0	0	−0.23806	0.307206
  3482	0	0	0.017378	0.267581
  3546	0	0	0.071637	0.321201
  3554	0	0	−0.10865	0.21563
  3620	0	0	−0.18183	0.230787
  3632	0	0	0.04804	0.247622
  3677	0	0	−0.14473	0.201314
  3683	0	0	0.00301	0.2633
  3686	0	0	−0.03852	0.375431
  3692	0	0	−0.59334	0.407906
  3711	0	0	−0.07697	0.1336
  3725	0	0	−0.1157	0.688963
  3746	0	0	−0.09686	0.406243
  3765	0	0	−0.38459	0.568063
  3785	0	0	−0.02761	0.586677
  3793	0	0	−0.01682	0.432956
  3800	0	0	0.093978	0.693084
  3804	0	0	0.149344	0.963817
  3812	0	0	0.078875	0.719019
  3836	0	0	0.245725	0.62927
  3876	0	0	−0.10377	0.245747
  3891	0	0	0.056743	0.30804
  3905	0	0	−0.18947	0.77305
  3935	0	0	−0.1837	0.688495
  3939	0	0	−0.13203	0.177443
  3946	0	0	−0.57596	0.119957
  3966	0	0	−0.14854	0.290791

• Tables 5a and 5b list 386 target genes, which are differentially expressed between CML blast crisis and normal immature CD34+ cells (p<0.1%) (the “target geneset”). The target genes are identified by their SEQ ID NOs in Tables 5a and 5b. Information for these genes is presented in Table 8. Table 5a lists target genes that that were not disclosed in U.S.Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 5b lists target genes that were also identified in U.S.Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.

• TABLE 5a
  CML target genes
  SEQID NO

  2
  8
  51
  74
  88
  99
  105
  109
  116
  142
  146
  158
  174
  184
  185
  191
  204
  246
  252
  261
  267
  298
  309
  312
  321
  337
  343
  359
  365
  370
  379
  390
  393
  432
  444
  483
  490
  493
  494
  495
  503
  506
  522
  562
  564
  565
  571
  576
  596
  600
  602
  605
  607
  615
  628
  629
  631
  638
  644
  659
  664
  665
  675
  676
  688
  700
  701
  727
  728
  730
  741
  745
  759
  766
  781
  788
  790
  809
  813
  843
  840
  841
  845
  847
  873
  878
  884
  900
  902
  906
  908
  915
  934
  960
  962
  983
  1000
  1012
  1014
  1020
  1027
  1036
  1051
  1054
  1067
  1089
  1093
  1106
  1112
  1132
  1138
  1140
  1145
  1158
  1160
  1161
  1164
  1165
  1183
  1188
  1197
  1202
  1223
  1245
  1254
  1288
  1300
  1306
  1308
  1311
  1325
  1331
  1334
  1346
  1352
  1380
  1400
  1409
  1410
  1411
  1415
  1416
  1440
  1441
  1446
  1452
  1456
  1464
  1472
  1489
  1495
  1500
  1502
  1503
  1522
  1527
  1532
  1534
  1575
  1596
  1608
  1614
  1643
  1652
  1674
  1689
  1711
  1712
  1713
  1724
  1728
  1756
  1757
  1762
  1767
  1772
  1781
  1785
  1798
  1799
  1800
  1802
  1803
  1813
  1828
  1849
  1870
  1873
  1893
  1910
  1926
  1927
  1944
  1990
  1991
  1998
  2007
  2011
  2023
  2032
  2040
  2042
  2056
  2064
  2082
  2085
  2101
  2104
  2136
  2161
  2162
  2174
  2188
  2200
  2206
  2211
  2212
  2213
  2218
  2224
  2248
  2252
  2253
  2266
  2279
  2304
  2310
  2312
  2313
  2320
  2329
  2356
  2372
  2388
  2406
  2442
  2454
  2462
  2469
  2479
  2505
  2525
  2534
  2554
  2561
  2563
  2565
  2567
  2591
  2600
  2631
  2632
  2649
  2654
  2658
  2664
  2665
  2670
  2676
  2696
  2699
  2721
  2726
  2734
  2739
  2766
  2775
  2777
  2788
  2810
  2824
  2825
  2830
  2842
  2862
  2863
  2864
  2892
  2894
  2900
  2903
  2921
  2928
  2938
  2953
  2964
  2967
  2981
  3003
  3019
  3020
  3027
  3029
  3047
  3048
  3067
  3075
  3085
  3093
  3094
  3097
  3103
  3136
  3185
  3191
  3194
  3196
  3215
  3222
  3238
  3240
  3241
  3245
  3248
  3254
  3279
  3312
  3329
  3339
  3348
  3361
  3364
  3373
  3380
  3395
  3396
  3398
  3400
  3402
  3428
  3456
  3462
  3470
  3500
  3514
  3533
  3538
  3555
  3569
  3582
  3583
  3611
  3628
  3640
  3642
  3646
  3650
  3655
  3658
  3685
  3689
  3696
  3718
  3755
  3763
  3792
  3844
  3845
  3849
  3857
  3880
  3901
  3915
  3937
  3940
  3955

• TABLE 5b
  CML target genes

  	SEQ ID NO	log(ratio) BC
  	1776	0
  	3961	0

• Genes that are not listed in Table 1a or 1b but which are functional equivalents of any gene listed in Table 1a or 1b can also be used with or in place of the gene listed in the table. A functional equivalent of a gene A refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA of gene A.
• In various specific embodiments, different numbers and subcombinations of the genes listed in Tables 1a and/or 1b are selected as the marker set, whose profile is used in the methods of the invention, as described in Section 5.2., infra. In various embodiments, all or a subset of those genes listed in each of Tables 2a and/or 2b or Table 3, supra, or their respective functional equivalents are used.
• In one embodiment, one or more genes that cluster together with one or more genes listed in a table can be selected to represent the cluster such that the marker set contains genes representing a plurality of different clusters.
• In a specific embodiment, measurements of gene products of the genes, respectively, shown in Tables 2a and/or 2b, or their respective functional equivalents, are used for CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Tables 2a and/or 2b are used.
• In another embodiment, measurements of the gene products of the set of 20 genes shown in Table 3 (which is a subset of the genes listed in Table 2a and Table 5a) or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15 or 20 of the genes listed in Table 3 are used.
• In another embodiment, measurements of the gene products of the set of 10 up-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the up-regulated genes listed in Table 3 are used.
• In another embodiment, measurements of the gene products of the set of 10 down-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the down-regulated genes listed in Table 3 are used.
• In still another embodiment, measurements of the genes, respectively, shown in Table 4 or their respective functional equivalents are used for determining imatinib resistance in a patient. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Table 4 are used. In a specific embodiment, imatinib resistance is determined according to the measurements of gene products of all or at least 5, 6, 7, or 8 of the genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.
• The invention also provides sets of promoter controlled genes, measurements of which can be used for evaluating the progression of CML in a patient. In one embodiment, measurements of the gene products of genes that are controlled by one or more of the promoters shown in Table 6 or their respective functional equivalents are used for evaluating CML progression. In a particular embodiment, measurements of gene products controlled by a promoter selected from the group consisting of set of promoters shown in Table 6 or their respective functional equivalents are used.

• TABLE 6
  Promoters associated with CML progression

  		EXPEC-
  PROMOTER	P-VALUE	TATION	SOURCE	SPECIES

  MZF_1-4	0	0	Genes with common	Homo
  			promoter sites	sapiens
  S8	1.22E−12	7.69E−11	Genes with common	Homo
  			promoter sites	sapiens
  deltaEF1	5.87E−11	3.70E−09	Genes with common	Homo
  			promoter sites	sapiens
  SPI-B	1.48E−10	9.35E−09	Genes with common	Homo
  			promoter sites	sapiens
  Yin-Yang	1.48E−09	9.30E−08	Genes with common	Homo
  			promoter sites	sapiens
  Ahr-ARNT	1.60E−09	1.01E−07	Genes with common	Homo
  			promoter sites	sapiens
  MZF_5-13	1.26E−06	7.96E−05	Genes with common	Homo
  			promoter sites	sapiens
  c-MYB_1	5.10E−06	0.000321	Genes with common	Homo
  			promoter sites	sapiens

• The invention provides methods for identifying a set of genes for evaluating stage/progression of CML. The methods make use of measured expression profiles of a plurality of genes (e.g., measurements of abundance levels of the corresponding gene products) in bone marrow or blood samples from a plurality of patients whose CML stage/progression status are known. As used herein, a patient is animal inflicted with CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In one embodiment, for each of the plurality of genes a metric of correlation between expression level of the gene and survival outcome in the plurality of CML patients is determined. One or more genes are then selected based on their metrics of correlation.
• Progression markers can be obtained by identifying genes whose expression levels are significantly different across CML patients of different phases of CML. In preferred embodiments, genes whose expression levels exhibit differences across different phrase groups to at least a predetermined level are selected as the genes whose expression levels correlate with CML phases. In one embodiment, the expression level differences among patients of different CML phases are evaluated using ANOVA. In one embodiment, a gene is selected if the p-value of the gene corresponds to a predetermined significance level, e.g., a p-value less than 10⁻¹¹.
• The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs, wherein said one or more programs cause the processor to carry out a method described above.
• The invention also provides a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, said computer program product comprising a computer readable storage medium having a computer program mechanism encoded thereon, wherein said computer program mechanism may be loaded into the memory of said computer and cause said computer to carry out a method described above.
5.2. Methods of Evaluating CML Progression and Responses
• The invention provides methods for determining the stage or progression status in a CML patient using a measured marker profile comprising measurements of the gene products of genes, e.g., the sets of genes described in Section 5.1., supra.
5.2.1. Methods for Evaluating Progression Based on Expression Profiles
• In preferred embodiments, the methods of the invention use a progression classifier, also called a classifier, for predicting CML progression and/or responsiveness to imatinib mesylate in a patient. The progression classifier can be based on any appropriate pattern recognition method that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs. The progression classifier can be trained with training data from a training population of CML patients. Typically, the training data comprise for each of the CML patients in the training population a training marker profile comprising measurements of respective gene products of a plurality of genes in a suitable sample taken from the patient and CML progression information. In a preferred embodiment, the training population comprises patients from each of the different stages of CML, i.e., CP-CML, ADV-CML, or AP-CML and BC-CML. In another preferred embodiment, the training population comprises patients from each of the different IM response groups, i.e., IM resistant and IM responsive.
• In preferred embodiments, the progression classifier can be based on a classification (pattern recognition) method described below, e.g., profile similarity (Section 5.2.1.1., infra); artificial neural network (Section 5.2.1.2., infra); support vector machine (SVM, Section 5.2.1.3., infra); logic regression (Section 5.2.1.4., infra), linear or quadratic discriminant analysis (Section 5.2.1.5., infra), decision trees (Section 5.2.1.6., infra), clustering (Section 5.2.1.7., infra), principal component analysis (Section 5.2.1.8., infra), nearest neighbor classifier analysis (Section 5.2.1.9., infra). Such progression classifiers can be trained with the training population using methods described in the relevant sections, infra.
• The marker profile can be obtained by measuring the plurality of gene products in a CML cell sample from the patient using a method known in the art, e.g., a method described in Section 5.2.4-5.2.5., infra.
• Various known statistical pattern recognition methods can be used in conjunction with the present invention. A progression classifier based on any of such methods can be constructed using the marker profiles and progression data of training patients. Such a progression classifier can then be used to evaluate the progression status of a CML patient based on the patient's marker profile. The methods can also be used to identify markers that discriminate between different progression status and/or imatinib resistance using a marker profile and progression and/or imatinib resistance data of training patients. For simplicity, the methods are often discussed with respect to evaluation of the progression status. It will be understood by a person skilled in the art that the methods are equally applicable to evaluation of IM responsiveness.
5.2.1.1. Profile Matching
• A patient's CML stage or progression status can be evaluated by comparing a marker profile obtained in a suitable sample from the patient with a marker profile that is representative of a particular CML phase. Such a marker profile is also termed a “template profile” or a “template.” The degree of similarity to such a template profile provides an evaluation of the patient's CML stage or progression status. If the degree of similarity of the patient marker profile and a template profile is above a predetermined threshold, the patient is assigned a CML phase or progression status represented by the template. For example, a patient's CML stage or progression status can be evaluated by comparing a marker profile of the patient to a predetermined template profile corresponding to a certain CML stage or progression status, e.g., an ADV-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of advanced phase patients or a CP-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of chronic phase patients.
• In one embodiment, the similarity is represented by a correlation coefficient between the patient's profile and the template. In one embodiment, a correlation coefficient above a correlation threshold indicates a high similarity, whereas a correlation coefficient below the threshold indicates a low similarity.
• In a specific embodiment, P_imeasures the similarity between the patient's profile {right arrow over (y)} and a template profile, e.g., a template profile comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}_CPor the ADV-CML template {right arrow over (z)}_ADV. Such a coefficient, P_i, can be calculated using the following equation:
• 
  P_i=({right arrow over (z)}_i·{right arrow over (y)})/(∥{right arrow over (z)}_i∥·∥{right arrow over (y)}∥)
• where i designates the ith template. For example, i is CP for CP-CML template. Thus, in one embodiment, {right arrow over (y)} is classified as a CP-CML profile if P_CPis greater than a selected correlation threshold. In another embodiment, {right arrow over (y)} is classified as an ADV-CML profile if P_ADVis greater than a selected correlation threshold. In preferred embodiments, the correlation threshold is set as 0.3, 0.4, 0.5 or 0.6. In another embodiment, {right arrow over (y)} is classified as a CP-CML profile if P_CPis greater than P_ADV, whereas {right arrow over (y)} is classified as a ADV-CML profile if P_CPis less than P_ADV.
• In another embodiment, the correlation coefficient is a weighted dot product of the patient's profile {right arrow over (y)} and a template profile, in which measurements of each different marker is assigned a weight.
• In another embodiment, similarity between a patient's profile and a template is represented by a distance between the patient's profile and the template. In one embodiment, a distance below a given value indicates high similarity, whereas a distance equal to or greater than the given value indicates low similarity.
• In one embodiment, the Euclidian distance according to the formula
• 
  D_i=∥{right arrow over (y)}−{right arrow over (z)}_i∥
• is used, where D_imeasures the distance between the patient's profile {right arrow over (y)} and a template profile comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}_CP, the ADV-CML template {right arrow over (z)}_ADVor the AP-CML template {right arrow over (z)}_APor BC-CML template {right arrow over (z)}_Bc. In other embodiments, the Euclidian distance is squared to place progressively greater weight on cellular constituents that are further apart. In alternative embodiments, the distance measure D_iis the Manhattan distance provide by
• $D_i=\sum _ny\left(n\right)-z_i\left(n\right)$
• where y(n) and z_i(n) are respectively measurements of the nth marker gene product in the patient's profile {right arrow over (y)} and a template profile.
• In another embodiment, the distance is defined as D_i=1−P_iwhere P_iis the correlation coefficient or normalized dot product as described above.
• In still other embodiments, the distance measure may be the Chebychev distance, the power distance, and percent disagreement, all of which are well known in the art.
• A distance based similarity measure is particularly useful for classifying advanced phase CML patients as either AP-CML or BC-CML since the marker profiles of AP-CML and BC-CML differ from each other in a quantitative rather than qualitative manner. Thus, in one embodiment, the invention provides a method for classifying an advanced phase CML patient as either AP-CML or BC-CML by comparing the distances between a marker profile of the patient with an AP-CML template and a BC-CML template, and classifying the patient as either AP-CML or BC-CML if the distance to the corresponding template is smaller.
• A person skilled in the art would understand that the above described methods can be applied to expression profiles of IM resistance genes for evaluation of IM responsiveness. For example, the methods can be used to compare a patient expression profile to IM resistance template and IM responsive template by calculating a P_imeasuring the similarity between the patient's profile {right arrow over (y)} and the IM resistance template comprising measurements of marker gene products representative of measurements of marker gene products in IM resistant patients, {right arrow over (z)}_resist, and/or IM responsive template comprising measurements of marker gene products representative of measurements of marker gene products in IM responsive patients, {right arrow over (z)}_resp. Such a coefficient, P_i, can be calculated using the equation described above.
5.2.1.2. Artificial Neural Network
• In some embodiments, a neural network is used to classify a patient marker profile. The neural network takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. A neural network can be constructed for a selected set of molecular markers of the invention. A neural network is a two-stage regression or classification model. A neural network has a layered structure that includes a layer of input units (and the bias) connected by a layer of weights to a layer of output units. For regression, the layer of output units typically includes just one output unit. However, neural networks can handle multiple quantitative responses in a seamless fashion.
• In multilayer neural networks, there are input units (input layer), hidden units (hidden layer), and output units (output layer). There is, furthermore, a single bias unit that is connected to each unit other than the input units. Neural networks are described in Duda et al., 2001, Pattern Classification, Second Edition, John Wiley & Sons, Inc., New York; and Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York.
• The basic approach to the use of neural networks is to start with an untrained network, present a training pattern, e.g., marker profiles from training patients, to the input layer, and to pass signals through the net and determine the output, e.g., the status of progression and/or the status of imatinib resistance in the training patients, at the output layer. These outputs are then compared to the target values; any difference corresponds to an error. This error or criterion function is some scalar function of the weights and is minimized when the network outputs match the desired outputs. Thus, the weights are adjusted to reduce this measure of error. For regression, this error can be sum-of-squared errors. For classification, this error can be either squared error or cross-entropy (deviation). See, e.g., Hastie et al., 2001,The Elements of Statistical Learning, Springer-Verlag, New York.
• Three commonly used training protocols are stochastic, batch, and on-line. In stochastic training, patterns are chosen randomly from the training set and the network weights are updated for each pattern presentation. Multilayer nonlinear networks trained by gradient descent methods such as stochastic back-propagation perform a maximum-likelihood estimation of the weight values in the model defined by the network topology. In batch training, all patterns are presented to the network before learning takes place. Typically, in batch training, several passes are made through the training data. In online training, each pattern is presented once and only once to the net.
• In some embodiments, consideration is given to starting values for weights. If the weights are near zero, then the operative part of the sigmoid commonly used in the hidden layer of a neural network (see, e.g., Hastie et al., 2001,The Elements of Statistical Learning, Springer-Verlag, New York) is roughly linear, and hence the neural network collapses into an approximately linear model. In some embodiments, starting values for weights are chosen to be random values near zero. Hence the model starts out nearly linear, and becomes nonlinear as the weights increase. Individual units localize to directions and introduce nonlinearities where needed. Use of exact zero weights leads to zero derivatives and perfect symmetry, and the algorithm never moves. Alternatively, starting with large weights often leads to poor solutions.
• Since the scaling of inputs determines the effective scaling of weights in the bottom layer, it can have a large effect on the quality of the final solution. Thus, in some embodiments, at the outset all expression values are standardized to have mean zero and a standard deviation of one. This ensures all inputs are treated equally in the regularization process, and allows one to choose a meaningful range for the random starting weights. With standardization inputs, it is typical to take random uniform weights over the range [−0.7, +0.7].
• A recurrent problem in the use of networks having a hidden layer is the optimal number of hidden units to use in the network. The number of inputs and outputs of a network are determined by the problem to be solved. In the present invention, the number of inputs for a given neural network can be the number of molecular markers in the selected set of molecular markers of the invention. The number of output for the neural network will typically be just one. However, in some embodiment more than one output is used so that more than just two states can be defined by the network. If too many hidden units are used in a neural network, the network will have too many degrees of freedom and is trained too long, there is a danger that the network will overfit the data. If there are too few hidden units, the training set cannot be learned. Generally speaking, however, it is better to have too many hidden units than too few. With too few hidden units, the model might not have enough flexibility to capture the nonlinearities in the data; with too many hidden units, the extra weight can be shrunk towards zero if appropriate regularization or pruning, as described below, is used. In typical embodiments, the number of hidden units is somewhere in the range of 5 to 100, with the number increasing with the number of inputs and number of training cases.
• One general approach to determining the number of hidden units to use is to apply a regularization approach. In the regularization approach, a new criterion function is constructed that depends not only on the classical training error, but also on classifier complexity. Specifically, the new criterion function penalizes highly complex models; searching for the minimum in this criterion is to balance error on the training set with error on the training set plus a regularization term, which expresses constraints or desirable properties of solutions:
• 
  J=J_pat+λJ_reg.
• The parameter λ is adjusted to impose the regularization more or less strongly. In other words, larger values for λ will tend to shrink weights towards zero: typically cross-validation with a validation set is used to estimate λ. This validation set can be obtained by setting aside a random subset of the training population. Other forms of penalty can also be used, for example the weight elimination penalty (see, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York).
• Another approach to determine the number of hidden units to use is to eliminate—prune—weights that are least needed. In one approach, the weights with the smallest magnitude are eliminated (set to zero). Such magnitude-based pruning can work, but is nonoptimal; sometimes weights with small magnitudes are important for learning and training data. In some embodiments, rather than using a magnitude-based pruning approach, Wald statistics are computed. The fundamental idea in Wald Statistics is that they can be used to estimate the importance of a hidden unit (weight) in a model. Then, hidden units having the least importance are eliminated (by setting their input and output weights to zero). Two algorithms in this regard are the Optimal Brain Damage (OBD) and the Optimal Brain Surgeon (OBS) algorithms that use second-order approximation to predict how the training error depends upon a weight, and eliminate the weight that leads to the smallest increase in training error.
• Optimal Brain Damage and Optimal Brain Surgeon share the same basic approach of training a network to local minimum error at weight w, and then pruning a weight that leads to the smallest increase in the training error. The predicted functional increase in the error for a change in full weight vector δw is:
• $\delta J={\left(\frac{\partial J}{\partial w}\right)}^t·\delta w+\frac{1}{2}\delta w^t·\frac{{\partial }^2J}{\partial {\mathrm{<figure-callout\; label="w"\; filenames="US20120072124A1-20120322-D00000.png,US20120072124A1-20120322-D00001.png"\; state="\{\{state\}\}">w</figure-callout>}}^2}·\delta w+O\left({\delta w}^3\right)$
• where
• $\frac{{\partial }^2J}{\partial {\mathrm{<figure-callout\; label="w"\; filenames="US20120072124A1-20120322-D00000.png,US20120072124A1-20120322-D00001.png"\; state="\{\{state\}\}">w</figure-callout>}}^2}$
• is the Hessian matrix. The first term vanishes because we are at a local minimum in error; third and higher order terms are ignored. The general solution for minimizing this function given the constraint of deleting one weight is:
• $\delta w=-\frac{w_q}{{\left[H^{-1}\right]}_{\mathrm{qq}}}H^{-1}·u_q\mathrm{and}L_q=\frac{1}{2}-\frac{w_q^2}{{\left[H^{-1}\right]}_{\mathrm{qq}}}$
• Here, u_qis the unit vector along the qth direction in weight space and L_qis approximation to the saliency of the weight q—the increase in training error if weight q is pruned and the other weights updated δw. These equations require the inverse of H. One method to calculate this inverse matrix is to start with a small value, H₀⁻¹=α⁻¹I, where α is a small parameter—effectively a weight constant. Next the matrix is updated with each pattern according to
• $H_{m+1}^{-1}=H_m^{-1}-\frac{H_m^{-1}X_{m+1}X_{m+1}^TH_m^{-1}}{\frac{n}{a_m}+X_{m+1}^TH_m^{-1}x_{m+1}}$
• where the subscripts correspond to the pattern being presented and a_mdecreases with m. After the full training set has been presented, the inverse Hessian matrix is given by H⁻¹=H_n⁻¹. In algorithmic form, the Optimal Brain Surgeon method is:

• 		begin initialize nH, w, θ
  		train a reasonably large network to minimum error
  		do compute H−1by Eqn. 1
  		$q^{*}\leftarrow \arg \underset{q}{\min }{\mathrm{<figure-callout\; label="w\; q"\; filenames="US20120072124A1-20120322-D00000.png,US20120072124A1-20120322-D00001.png"\; state="\{\{state\}\}">w</figure-callout>}}_q^{}\text{/}\left({2\left[H^{-1}\right]}_{\mathrm{qq}}\right)\left(\mathrm{saliency}L_q\right)$
  		$w\leftarrow w-\frac{w_{q^{*}}}{{\left[H^{-1}\right]}_{q^{*}q^{*}}}H^{-1}e_{q^{*}}\left(\mathrm{saliency}L_q\right)$
  		until J(w) > θ
  		return w
  		end

• The Optimal Brain Damage method is computationally simpler because the calculation of the inverse Hessian matrix inline 3 is particularly simple for a diagonal matrix. The above algorithm terminates when the error is greater than a criterion initialized to be θ. Another approach is to changeline 6 to terminate when the change in J(w) due to elimination of a weight is greater than some criterion value.
• In some embodiments, a back-propagation neural network (see, for example Abdi, 1994, “A neural network primer”, J. Biol System. 2, 247-283) containing a single hidden layer of ten neurons (ten hidden units) found in EasyNN-Plus version 4.0 g software package (Neural Planner Software Inc.) is used. In a specific example, parameter values within the EasyNN-Plus program are set as follows: a learning rate of 0.05, and a momentum of 0.2. In some embodiments in which the EasyNN-Plus version 4.0 g software package is used, “outlier” samples are identified by performing twenty independently-seeded trials involving 20,000 learning cycles each.
5.2.1.3. Support Vector Machine
• In some embodiments of the present invention, support vector machines (SVMs) are used to classify subjects using expression profiles of marker genes described in the present invention. The SVM takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. General description of SVM can be found in, for example, Cristianini and Shawe-Taylor, 2000, An Introduction to Support Vector Machines, Cambridge University Press, Cambridge, Boser et al., 1992, “A training algorithm for optimal margin classifiers, inProceedings of the5^thAnnual ACM Workshop on Computational Learning Theory, ACM Press, Pittsburgh, Pa., pp. 142-152; Vapnik, 1998, Statistical Learning Theory, Wiley, New York; Duda,Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.; Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; and Furey et al., 2000, Bioinformatics 16, 906-914. Applications of SVM in biological applications are described in Jaakkola et al.,Proceedings of the7^thInternational Conference on Intelligent Systems for Molecular Biology, AAAI Press, Menlo Park, Calif. (1999); Brown et al.,Proc. Natl. Acad. Sci.97(1):262-67 (2000); Zien et al.,Bioinformatics,16(9):799-807 (2000); Furey et al.,Bioinformatics,16(10):906-914 (2000)
• In one approach, when a SVM is used, the gene expression data is standardized to have mean zero and unit variance and the members of a training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a selected set of genes of the present invention is used to train the SVM. Then the ability for the trained SVM to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given selected set of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the SVM computation.
• Support vector machines map a given set of binary labeled training data to a high-dimensional feature space and separate the two classes of data with a maximum margin hyperplane. In general, this hyperplane corresponds to a nonlinear decision boundary in the input space. Let XεR₀⊂

  

  ⁿbe the input vectors, yε{−1,+1} be the labels, and φ: R₀→F be the mapping from input space to feature space. Then the SVM learning algorithm finds a hyperplane (w,b) such that the quantity
• $\gamma =\underset{i}{\min }y_i\left\{〈w,\phi \left(X_i\right)〉-b\right\}$
• is maximized, where the vector w has the same dimensionality as F, b is a real number, and γ is called the margin. The corresponding decision function is then
• 
  ƒ(X)=sign(

  

  w,φ(X)

  

  −b)
• This minimum occurs when
• $w=\sum _i{\alpha }_iy_i\phi \left(X_i\right)$
• where {α_i} are positive real numbers that maximize
• $\sum _i{\alpha }_i-\sum _{\mathrm{ij}}{\alpha }_i{\alpha }_jy_iy_j〈\phi \left(X_i\right),\phi \left(X_j\right)〉$
• subject to
• $\sum _i{\alpha }_iy_i=0,{\alpha }_i>0$
• The decision function can equivalently be expressed as
• $f\left(X\right)=\mathrm{sign}(\sum _i{\alpha }_iy_i〈\phi (X_i,\phi \left(X\right)〉-b)$
• From this equation it can be seen that the α_iassociated with the training point X_iexpresses the strength with which that point is embedded in the final decision function. A remarkable property of this alternative representation is that only a subset of the points will be associated with a non-zero α_i. These points are called support vectors and are the points that lie closest to the separating hyperplane. The sparseness of the α vector has several computational and learning theoretic consequences. It is important to note that neither the learning algorithm nor the decision function needs to represent explicitly the image of points in the feature space, φ(X_i), since both use only the dot products between such images,

  

  φ(X_i),φ(X_j)

  

  . Hence, if one were given a function K(X,Y)=

  

  φ(X),φ(X)

  

  , one could learn and use the maximum margin hyperplane in the feature space without ever explicitly performing the mapping. For each continuous positive definite function K(X,Y) there exists a mapping φ such that K(X,Y)=

  

  φ(X),φ(X)

  

  for all X, YεR₀(Mercer's Theorem). The function K(X,Y) is called the kernel function. The use of a kernel function allows the support vector machine to operate efficiently in a nonlinear high-dimensional feature spaces without being adversely affected by the dimensionality of that space. Indeed, it is possible to work with feature spaces of infinite dimension. Moreover, Mercer's theorem makes it possible to learn in the feature space without even knowing φ and F. The matrix K_ij=

  

  φ(X_i),φ(X_j)

  

  is called the kernel matrix. Finally, note that the learning algorithm is a quadratic optimization problem that has only a global optimum. The absence of local minima is a significant difference from standard pattern recognition techniques such as neural networks. For moderate sample sizes, the optimization problem can be solved with simple gradient descent techniques. In the presence of noise, the standard maximum margin algorithm described above can be subject to overfitting, and more sophisticated techniques should be used. This problem arises because the maximum margin algorithm always finds a perfectly consistent hypothesis and does not tolerate training error. Sometimes, however, it is necessary to trade some training accuracy for better predictive power. The need for tolerating training error has led to the development the soft-margin and the margin-distribution classifiers. One of these techniques replaces the kernel matrix in the training phase as follows:
• 
  K←K+λI
• while still using the standard kernel function in the decision phase. By tuning λ, one can control the training error, and it is possible to prove that the risk of misclassifying unseen points can be decreased with a suitable choice of λ.
• If instead of controlling the overall training error one wants to control the trade-off between false positives and false negatives, it is possible to modify K as follows:
• 
  K←K+λD
• where D is a diagonal matrix whose entries are either d⁺ or d⁻, in locations corresponding to positive and negative examples. It is possible to prove that this technique is equivalent to controlling the size of the α_iin a way that depends on the size of the class, introducing a bias for larger α_iin the class with smaller d. This in turn corresponds to an asymmetric margin; i.e., the class with smaller d will be kept further away from the decision boundary. In some cases, the extreme imbalance of the two classes, along with the presence of noise, creates a situation in which points from the minority class can be easily mistaken for mislabelled points. Enforcing a strong bias against training errors in the minority class provides protection against such errors and forces the SVM to make the positive examples support vectors. Thus, choosing
• $d^{+}=\frac{1}{n^{+}}\mathrm{and}d^{-}=\frac{1}{n^{-}}$
• provides a heuristic way to automatically adjust the relative importance of the two classes, based on their respective cardinalities. This technique effectively controls the trade-off between sensitivity and specificity.
• In the present invention, a linear kernel can be used. The similarity between two marker profiles X and Y can be the dot product X·Y. In one embodiment, the kernel is
• 
  K(X,Y)=X·Y+1
• In another embodiment, a kernel of degree d is used
• 
  K(X,Y)=(X·Y+1)^d, wheredcan be either 2, 3, . . .
• In still another embodiment, a Gaussian kernel is used
• $K\left(X,Y\right)=\exp \left(\frac{-{X-Y}^2}{2{\sigma }^2}\right)$
• where σ is the width of the Gaussian.
5.2.1.4. Logistic Regression
• In some embodiments, the progression classifier is based on a regression model, preferably a logistic regression model. Such a regression model includes a coefficient for each of the molecular markers in a selected set of molecular markers of the invention. In such embodiments, the coefficients for the regression model are computed using, for example, a maximum likelihood approach. In particular embodiments, molecular marker data from two different clinical groups, e.g., chronic phase and advanced phase or imatinib resistant and imatinib sensitive, is used and the dependent variable is the clinical status of the patient for which molecular marker characteristic data are from.
• Some embodiments of the present invention provide generalizations of the logistic regression model that handle multicategory (polychotomous) responses. Such embodiments can be used to discriminate an organism into one or three or more clinical groups, e.g., chronic phase, accelerated phase, and blast phase. Such regression models use multicategory logit models that simultaneously refer to all pairs of categories, and describe the odds of response in one category instead of another. Once the model specifies logits for a certain (J-1) pairs of categories, the rest are redundant. See, for example, Agresti,An Introduction to Categorical Data Analysis, John Wiley & Sons, Inc., 1996, New York,Chapter 8, which is hereby incorporated by reference.
5.2.1.5. Discriminant Analysis
• Linear discriminant analysis (LDA) attempts to classify a subject into one of two categories based on certain object properties. In other words, LDA tests whether object attributes measured in an experiment predict categorization of the objects. LDA typically requires continuous independent variables and a dichotomous categorical dependent variable. In the present invention, the expression values for the selected set of molecular markers of the invention across a subset of the training population serve as the requisite continuous independent variables. The clinical group classification of each of the members of the training population serves as the dichotomous categorical dependent variable.
• LDA seeks the linear combination of variables that maximizes the ratio of between-group variance and within-group variance by using the grouping information. Implicitly, the linear weights used by LDA depend on how the expression of a molecular marker across the training set separates in the two groups (e.g., a group that has CP-CML and a group that have ADV-CMP) and how this gene expression correlates with the expression of other genes. In some embodiments, LDA is applied to the data matrix of the N members in the training sample by K genes in a combination of genes described in the present invention. Then, the linear discriminant of each member of the training population is plotted. Ideally, those members of the training population representing a first subgroup (e.g. those subjects that have CP-CML) will cluster into one range of linear discriminant values (e.g., negative) and those member of the training population representing a second subgroup (e.g. those subjects that have ADV-CML) will cluster into a second range of linear discriminant values (e.g., positive). The LDA is considered more successful when the separation between the clusters of discriminant values is larger. For more information on linear discriminant analysis, see Duda,Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; Venables & Ripley, 1997, Modern Applied Statistics with s-plus, Springer, N.Y.
• Quadratic discriminant analysis (QDA) takes the same input parameters and returns the same results as LDA. QDA uses quadratic equations, rather than linear equations, to produce results. LDA and QDA are interchangeable, and which to use is a matter of preference and/or availability of software to support the analysis. Logistic regression takes the same input parameters and returns the same results as LDA and QDA.
5.2.1.6. Decision Trees
• In some embodiments of the present invention, decision trees are used to classify patients using expression data for a selected set of molecular markers of the invention. Decision tree algorithms belong to the class of supervised learning algorithms. The aim of a decision tree is to induce a classifier (a tree) from real-world example data. This tree can be used to classify unseen examples which have not been used to derive the decision tree.
• A decision tree is derived from training data. An example contains values for the different attributes and what class the example belongs. In one embodiment, the training data is expression data for a combination of genes described in the present invention across the training population.
• The following algorithm describes a decision tree derivation:

• Tree(Examples,Class,Attributes)
  Create a root node
  If all Examples have the same Class value, give the
  root this label
  Else if Attributes is empty label the root according to the
  most common value
  Else begin
  Calculate the information gain for each attribute
  Select the attribute A with highest information gain and
  make this the root attribute
  For each possible value, v, of this attribute
  Add a new branch below the root, corresponding to A = v
  Let Examples(v) be those examples with A = v
  If Examples(v) is empty, make the new branch a leaf node
  labeled with the most common value among Examples
  Else let the new branch be the tree created by
  Tree(Examples(v),Class,Attributes - {A})
  end

  
  A more detailed description of the calculation of information gain is shown in the following. If the possible classes v_iof the examples have probabilities P(v_i) then the information content I of the actual answer is given by:
• $I\left(P\left(v_1\right),\dots ,P\left(v_n\right)\right)=\sum _{i=1}^n-P\left(v_i\right){\mathrm{<figure-callout\; label="log"\; filenames="US20120072124A1-20120322-D00000.png,US20120072124A1-20120322-D00001.png"\; state="\{\{state\}\}">log</figure-callout>}}_2P\left(v_i\right)$
• The I-value shows how much information we need in order to be able to describe the outcome of a classification for the specific dataset used. Supposing that the dataset contains p positive (e.g. has ADV-CML) and n negative (e.g. has CP-CML) examples (e.g. individuals), the information contained in a correct answer is:
• $I\left(\frac{p}{p+n},\frac{n}{p+n}\right)=-\frac{p}{p+n}{\mathrm{<figure-callout\; label="log"\; filenames="US20120072124A1-20120322-D00000.png,US20120072124A1-20120322-D00001.png"\; state="\{\{state\}\}">log</figure-callout>}}_2\frac{p}{p+n}-\frac{n}{p+n}{\mathrm{<figure-callout\; label="log"\; filenames="US20120072124A1-20120322-D00000.png,US20120072124A1-20120322-D00001.png"\; state="\{\{state\}\}">log</figure-callout>}}_2\frac{n}{p+n}$
• where log₂is the logarithm using base two. By testing single attributes the amount of information needed to make a correct classification can be reduced. The remainder for a specific attribute A (e.g. a gene) shows how much the information that is needed can be reduced.
• $\mathrm{Remainder}\left(A\right)=\sum _{i=1}^v\frac{p_i+n_i}{p+n}I\left(\frac{p_i}{p_i+n_i},\frac{n_i}{p_i+n_i}\right)$
• “v” is the number of unique attribute values for attribute A in a certain dataset, “i” is a certain attribute value, “p_i” is the number of examples for attribute A where the classification is positive (e.g. cancer), “n_i” is the number of examples for attribute A where the classification is negative (e.g. healthy).
• The information gain of a specific attribute A is calculated as the difference between the information content for the classes and the remainder of attribute A:
• $\mathrm{Gain}\left(A\right)=I\left(\frac{p}{p+n},\frac{n}{p+n}\right)-\mathrm{Remainder}\left(A\right)$
• The information gain is used to evaluate how important the different attributes are for the classification (how well they split up the examples), and the attribute with the highest information.
• In general there are a number of different decision tree algorithms, many of which are described in Duda,Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc. Decision tree algorithms often require consideration of feature processing, impurity measure, stopping criterion, and pruning. Specific decision tree algorithms include, cut are not limited to classification and regression trees (CART), multivariate decision trees, ID3, and C4.5.
• In one approach, when an exemplary embodiment of a decision tree is used, the gene expression data for a selected set of molecular markers of the invention across a training population is standardized to have mean zero and unit variance. The members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a select combination of genes described in the present invention is used to construct the decision tree. Then, the ability for the decision tree to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given combination of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the decision tree computation.
5.2.1.7. Clustering
• In some embodiments, the expression values for a selected set of molecular markers of the invention are used to cluster a training set. For example, consider the case in which ten genes described in the present invention are used. Each member m of the training population will have expression values for each of the ten genes. Such values from a member m in the training population define the vector:

• X1m	X2m	X3m	X4m	X5m	X6m	X7m	X8m	X9m	X10m

  
  where X_imis the expression level of the i^thgene in organism m. If there are m organisms in the training set, selection of i genes will define m vectors. Note that the methods of the present invention do not require that each the expression value of every single gene used in the vectors be represented in every single vector m. In other words, data from a subject in which one of the i^thgenes is not found can still be used for clustering. In such instances, the missing expression value is assigned either a “zero” or some other normalized value. In some embodiments, prior to clustering, the gene expression values are normalized to have a mean value of zero and unit variance.
• Those members of the training population that exhibit similar expression patterns across the training group will tend to cluster together. A particular combination of genes of the present invention is considered to be a good classifier in this aspect of the invention when the vectors cluster into the trait groups found in the training population. For instance, if the training population includes patients with chronic phase and advanced phase CML, a clustering classifier will cluster the population into two groups, with each group uniquely representing either chronic phase or advanced phase.
• Clustering is described on pages 211-256 of Duda and Hart,Pattern Classification and Scene Analysis,1973, John Wiley & Sons, Inc., New York. As described in Section 6.7 of Duda, the clustering problem is described as one of finding natural groupings in a dataset. To identify natural groupings, two issues are addressed. First, a way to measure similarity (or dissimilarity) between two samples is determined. This metric (similarity measure) is used to ensure that the samples in one cluster are more like one another than they are to samples in other clusters. Second, a mechanism for partitioning the data into clusters using the similarity measure is determined.
• Similarity measures are discussed in Section 6.7 of Duda, where it is stated that one way to begin a clustering investigation is to define a distance function and to compute the matrix of distances between all pairs of samples in a dataset. If distance is a good measure of similarity, then the distance between samples in the same cluster will be significantly less than the distance between samples in different clusters. However, as stated on page 215 of Duda, clustering does not require the use of a distance metric. For example, a nonmetric similarity function s(x, x′) can be used to compare two vectors x and x′. Conventionally, s(x, x′) is a symmetric function whose value is large when x and x′ are somehow “similar”. An example of a nonmetric similarity function s(x, x′) is provided on page 216 of Duda.
• Once a method for measuring “similarity” or “dissimilarity” between points in a dataset has been selected, clustering requires a criterion function that measures the clustering quality of any partition of the data. Partitions of the data set that extremize the criterion function are used to cluster the data. See page 217 of Duda. Criterion functions are discussed in Section 6.8 of Duda.
• More recently, Duda et al., Pattern Classification, 2^ndedition, John Wiley & Sons, Inc. New York, has been published. Pages 537-563 describe clustering in detail. More information on clustering techniques can be found in Kaufman and Rousseeuw, 1990,Finding Groups in Data: An Introduction to Cluster Analysis, Wiley, New York, N.Y.; Everitt, 1993, Cluster analysis(3d ed.), Wiley, New York, N.Y.; and Backer, 1995,Computer-Assisted Reasoning in Cluster Analysis, Prentice Hall, Upper Saddle River, N.J. Particular exemplary clustering techniques that can be used in the present invention include, but are not limited to, hierarchical clustering (agglomerative clustering using nearest-neighbor algorithm, farthest-neighbor algorithm, the average linkage algorithm, the centroid algorithm, or the sum-of-squares algorithm), k-means clustering, fuzzy k-means clustering algorithm, and Jarvis-Patrick clustering.
5.2.1.8. Principal Component Analysis
• Principal component analysis (PCA) has been proposed to analyze gene expression data. Principal component analysis is a classical technique to reduce the dimensionality of a data set by transforming the data to a new set of variable (principal components) that summarize the features of the data. See, for example, Jolliffe, 1986, Principal Component Analysis, Springer, N.Y. Principal components (PCs) are uncorrelate and are ordered such that the k^thPC has the kth largest variance among PCs. The k^thPC can be interpreted as the direction that maximizes the variation of the projections of the data points such that it is orthogonal to the first k−1 PCs. The first few PCs capture most of the variation in the data set. In contrast, the last few PCs are often assumed to capture only the residual ‘noise’ in the data.
• PCA can also be used to create a progression classifier in accordance with the present invention. In such an approach, vectors for a selected set of molecular markers of the invention can be constructed in the same manner described for clustering above. In fact, the set of vectors, where each vector represents the expression values for the select genes from a particular member of the training population, can be considered a matrix. In some embodiments, this matrix is represented in a Free-Wilson method of qualitative binary description of monomers (Kubinyi, 1990, 3D QSAR in drug design theory methods and applications, Pergamon Press, Oxford, pp 589-638), and distributed in a maximally compressed space using PCA so that the first principal component (PC) captures the largest amount of variance information possible, the second principal component (PC) captures the second largest amount of all variance information, and so forth until all variance information in the matrix has been accounted for.
• Then, each of the vectors (where each vector represents a member of the training population) is plotted. Many different types of plots are possible. In some embodiments, a one-dimensional plot is made. In this one-dimensional plot, the value for the first principal component from each of the members of the training population is plotted. In this form of plot, the expectation is that members of a first group (e.g. chronic phase patients) will cluster in one range of first principal component values and members of a second group (e.g., advance phase patients) will cluster in a second range of first principal component values.
• In one example, the training population comprises two groups: chronic phase patients and advanced phase patients or imatinib resistant and imatinib sensitive. The first principal component is computed using the molecular marker expression values for the select genes of the present invention across the entire training population data set. Then, each member of the training set is plotted as a function of the value for the first principal component. In this example, those members of the training population in which the first principal component is positive are the chronic phase (or imatinib sensitive) patients and those members of the training population in which the first principal component is negative are advanced phase (or imatinib resistant) patients.
• In some embodiments, the members of the training population are plotted against more than one principal component. For example, in some embodiments, the members of the training population are plotted on a two-dimensional plot in which the first dimension is the first principal component and the second dimension is the second principal component. In such a two-dimensional plot, the expectation is that members of each subgroup represented in the training population will cluster into discrete groups. For example, a first cluster of members in the two-dimensional plot will represent subjects with CP-CML, a second cluster of members in the two-dimensional plot will represent subjects with ADV-CML, and so forth.
• In some embodiments, the members of the training population are plotted against more than two principal components and a determination is made as to whether the members of the training population are clustering into groups that each uniquely represents a subgroup found in the training population. In some embodiments, principal component analysis is performed by using the R mva package (Anderson, 1973, Cluster Analysis for applications, Academic Press, New York 1973; Gordon, Classification, Second Edition, Chapman and Hall, CRC, 1999.). Principal component analysis is further described in Duda,Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.
5.2.1.9. Nearest Neighbor Classifier Analysis
• Nearest neighbor classifiers are memory-based and require no model to be fit. Given a query point x₀, the k training points x_(r), r, . . . , k closest in distance to x₀are identified and then the point x₀is classified using the k nearest neighbors. Ties can be broken at random.
• In some embodiments, Euclidean distance in feature space is used to determine distance as:
• 
  d_(i)=∥x_(i)−x₀∥.
• Typically, when the nearest neighbor algorithm is used, the expression data used to compute the linear discriminant is standardized to have mean zero andvariance 1. In the present invention, the members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. Profiles of a selected set of molecular markers of the invention represents the feature space into which members of the test set are plotted. Next, the ability of the training set to correctly characterize the members of the test set is computed. In some embodiments, nearest neighbor computation is performed several times for a given combination of genes of the present invention. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of genes is taken as the average of each such iteration of the nearest neighbor computation.
• The nearest neighbor rule can be refined to deal with issues of unequal class priors, differential misclassification costs, and feature selection. Many of these refinements involve some form of weighted voting for the neighbors. For more information on nearest neighbor analysis, see Duda,Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.
5.2.1.10. Evolutionary Methods
• Inspired by the process of biological evolution, evolutionary methods of classifier design employ a stochastic search for an optimal classifier. In broad overview, such methods create several classifiers—a population—from measurements of gene products of the present invention. Each classifier varies somewhat from the other. Next, the classifiers are scored on expression data across the training population. In keeping with the analogy with biological evolution, the resulting (scalar) score is sometimes called the fitness. The classifiers are ranked according to their score and the best classifiers are retained (some portion of the total population of classifiers). Again, in keeping with biological terminology, this is called survival of the fittest. The classifiers are stochastically altered in the next generation—the children or offspring. Some offspring classifiers will have higher scores than their parent in the previous generation, some will have lower scores. The overall process is then repeated for the subsequent generation: The classifiers are scored and the best ones are retained, randomly altered to give yet another generation, and so on. In part, because of the ranking, each generation has, on average, a slightly higher score than the previous one. The process is halted when the single best classifier in a generation has a score that exceeds a desired criterion value. More information on evolutionary methods is found in, for example, Duda,Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.
5.2.1.11. Bagging, Boosting and the Random Subspace Method
• Bagging, boosting and the random subspace method are combining techniques that can be used to improve weak classifiers. These techniques are designed for, and usually applied to, decision trees. In addition, Skurichina and Duin provide evidence to suggest that such techniques can also be useful in linear discriminant analysis.
• In bagging, one samples the training set, generating random independent bootstrap replicates, constructs the classifier on each of these, and aggregates them by a simple majority vote in the final decision rule. See, for example, Breiman, 1996, Machine Learning 24, 123-140; and Efron & Tibshirani,An Introduction to Bootstrap, Chapman & Hall, New York, 1993.
• In boosting, classifiers are constructed on weighted versions of the training set, which are dependent on previous classification results. Initially, all objects have equal weights, and the first classifier is constructed on this data set. Then, weights are changed according to the performance of the classifier. Erroneously classified objects (molecular markers in the data set) get larger weights, and the next classifier is boosted on the reweighted training set. In this way, a sequence of training sets and classifiers is obtained, which is then combined by simple majority voting or by weighted majority voting in the final decision. See, for example, Freund & Schapire, “Experiments with a new boosting algorithm,”Proceedings 13^thInternational Conference on Machine Learning, 1996, 148-156.
• To illustrate boosting, consider the case where there are two phenotypic groups exhibited by the population under study, phenotype 1 (e.g., advanced phase patients), and phenotype 2 (e.g., chronic phase patients). Given a vector of molecular markers X, a classifier G(X) produces a prediction taking one of the type values in the two value set: {phenotype 1, phenotype 2}. The error rate on the training sample is
• $\stackrel{\_}{\mathrm{err}}=\frac{1}{N}\sum _{i=1}^NI\left(y_i\ne G\left(x_i\right)\right)$
• where N is the number of subjects in the training set (the sum total of the subjects that have eitherphenotype 1 or phenotype 2).
• A weak classifier is one whose error rate is only slightly better than random guessing. In the boosting algorithm, the weak classification algorithm is repeatedly applied to modified versions of the data, thereby producing a sequence of weak classifiers G_m(x), m,=1, 2, . . . , M. The predictions from all of the classifiers in this sequence are then combined through a weighted majority vote to produce the final prediction:
• $G\left(x\right)=\mathrm{sign}\left(\sum _{m=1}^M{\alpha }_mG_m\left(x\right)\right)$
• Here α₁, α₂, . . . , α_Mare computed by the boosting algorithm and their purpose is to weigh the contribution of each respective G_m(x). Their effect is to give higher influence to the more accurate classifiers in the sequence.
• The data modifications at each boosting step consist of applying weights w₁, w₂, . . . , w_nto each of the training observations (x_i, y_i), i=1, 2, . . . , N. Initially all the weights are set to w_i=1/N, so that the first step simply trains the classifier on the data in the usual manner. For each successive iteration m=2, 3, . . . , M the observation weights are individually modified and the classification algorithm is reapplied to the weighted observations. At stem m, those observations that were misclassified by the classifier G_m-1(x) induced at the previous step have their weights increased, whereas the weights are decreased for those that were classified correctly. Thus as iterations proceed, observations that are difficult to correctly classify receive ever-increasing influence. Each successive classifier is thereby forced to concentrate on those training observations that are missed by previous ones in the sequence.
• The exemplary boosting algorithm is summarized as follows:

• 1. Initialize the observation weights wi= 1/N, i = 1, 2, . . . , N.
  2. For m = 1 to M:
  (a) Fit a classifier Gm(x) to the training set using weights wi.
  (b) Compute
  ${\mathrm{err}}_m=\frac{\sum _{i=1}^Nw_iI\left(y_i\ne G_m\left(x_i\right)\right)}{\sum _{i=1}^Nw_i}$
  (c) Compute αm= log((l − errm)/errm).
  (d) Set wi← wi· exp[αm· I(yi≠ Gm(xi))], i = 1, 2, . . . , N.
  $3.\mathrm{Output}G\left(x\right)=\mathrm{sign}\lfloor \sum _{m=1}^M{\alpha }_mG_m\left(x\right)\rfloor$

  
  In the algorithm, the current classifier G_m(x) is induced on the weighted observations at line 2a. The resulting weighted error rate is computed at line 2b. Line 2c calculates the weight α_mgiven to G_m(x) in producing the final classifier G(x) (line 3). The individual weights of each of the observations are updated for the next iteration at line 2d. Observations misclassified by G_m(x) have their weights scaled by a factor exp(α_m), increasing their relative influence for inducing the next classifier G_m+1/(x) in the sequence. In some embodiments, modifications of the Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, boosting method are used. See, for example, Hasti et al.,The Elements of Statistical Learning,2001, Springer, N.Y.,Chapter 10. In some embodiments, boosting or adaptive boosting methods are used.
• In some embodiments, modifications of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, are used. For example, in some embodiments, feature preselection is performed using a technique such as the nonparametric scoring methods of Park et al., 2002, Pac. Symp. Biocomput. 6, 52-63. Feature preselection is a form of dimensionality reduction in which the genes that discriminate between classifications the best are selected for use in the classifier. Then, the LogitBoost procedure introduced by Friedman et al., 2000, Ann Stat 28, 337-407 is used rather than the boosting procedure of Freund and Schapire. In some embodiments, the boosting and other classification methods of Ben-Dor et al., 2000, Journal of Computational Biology 7, 559-583 are used in the present invention. In some embodiments, the boosting and other classification methods of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, 119-139, are used.
• In the random subspace method, classifiers are constructed in random subspaces of the data feature space. These classifiers are usually combined by simple majority voting in the final decision rule. See, for example, Ho, “The Random subspace method for constructing decision forests,” IEEE Trans Pattern Analysis and Machine Intelligence, 1998; 20(8): 832-844.
5.2.1.12. Other Algorithms
• The pattern classification and statistical techniques described above are merely examples of the types of models that can be used to construct a model for classification. Moreover, combinations of the techniques described above can be used. Some combinations, such as the use of the combination of decision trees and boosting, have been described. However, many other combinations are possible. In addition, in other techniques in the art such as Projection Pursuit and Weighted Voting can be used to construct a progression classifier.
5.2.2. Methods of Determining Aberrant Regulation of CML Target Genes
• The invention also provides methods and compositions for determining aberrant regulation in CML target genes and/or their encoded proteins. Such information can be used to determine a treatment regimen for a patient. For example, patients who have a defective regulation of a CML target gene can be identified. A treatment regimen including a therapy to regulate the gene can be prescribed to the patient. Thus, the invention provides methods and composition for assigning treatment regimen for a cancer patient. The invention also provides methods and composition for monitoring treatment progress for a CML patient based on the status of one or more of the CML target proteins.
• A variety of methods can be employed for the diagnostic and prognostic evaluation of patients for their status of CML target genes or proteins. In one embodiment, measurements of expression level of one or more of the CML target genes listed in Tables 5a and 5b, and/or abundance or activity level the encoded proteins are used. One or more of these genes or proteins having a level of expression or activity deviated from a respective predetermined threshold indicate aberrant regulation of the genes or proteins.
• In one embodiment, the method comprises determining an expression level of a CML target gene (a gene listed in Table 5a or 5b) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and the expression level deviated from a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated CML target gene or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated CML target gene. In another embodiment, the method comprises determining a level of abundance of a CML target protein, i.e., a protein encoded by a CML target gene, in a sample from a patient, and determining whether the level of abundance is deviated a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. In still another embodiment, the method comprises determining a level of activity of a protein encoded by the CML target gene in a sample of a patient, and determining whether the level of activity is deviated a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. A reduced activity may be a result of mutation of the CML target gene. Thus, the invention also provides a method for evaluating the status of CML target in a patient, comprising determining a mutation in a CML target gene or a protein encoded by the CML target gene in a sample from the patient, and the detection of a mutation causing the activity of the CML target protein to deviate from a predetermined threshold level indicates aberrant regulation of the protein in the patient. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated CML target protein or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated CML target protein. In the foregoing embodiments, and the embodiments described below, the sample can be an ex vivo cell sample, e.g., cells in a cell culture, or in vivo cells.
• In a specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the up-regulated genes listed in Table 3 (which is a subset of the genes listed in Table 5a) in the sample of a patient, and determining whether the expression level is above a predetermined threshold, and an expression level above a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the up-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is above a predetermined threshold, and a level of abundance of the protein above a predetermined threshold level indicates aberrant regulation of the protein in the patient.
• In another specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the down-regulated genes listed in Table 3 in the sample of a patient, and determining whether the expression level is below a predetermined threshold, and an expression level below a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is a level less than 50%, 25%, 10% or 1% of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the down-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is below a predetermined threshold, and a level of abundance of the protein below a predetermined threshold level indicates aberrant regulation of the protein in the patient.
• In one embodiment, the method comprises determining an expression level of an imatinib resistance gene (a gene listed in Table 4) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and an expression level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated imatinib resistance gene or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated imatinib resistance gene. In another embodiment, the method comprises determining a level of abundance of an imatinib resistance protein, i.e., a protein encoded by an imatinib resistance gene, in a sample from a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. In still another embodiment, the method comprises determining a level of activity of a protein encoded by an imatinib resistance gene in a sample of a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Such reduce activity may be a result of mutation of the imatinib resistance gene. Thus, the invention also provides a method for evaluating imatinib resistance in a patient, comprising determining a mutation in an imatinib resistance gene or a protein encoded by the imatinib resistance gene in a sample from the patient, and the detection of a mutation causing the activity of the imatinib resistance protein to deviate from a predetermined threshold level indicates the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated imatinib resistance protein or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated imatinib resistance protein.
• In a specific embodiment, imatinib resistance is determined according to the expression levels of one or more genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.
• Such methods may, for example, utilize reagents such as nucleotide sequences and antibodies, e.g., the CML progression nucleotide sequences, and antibodies directed against CML progression proteins, including peptide fragments thereof. Specifically, such reagents may be used, for example, for: (1) the detection of the presence of mutations in a CML progression gene, or the detection of either over- or under-expression of a CML progression gene relative to the normal expression level; and (2) the detection of either an over- or an under-abundance of a CML progression protein relative to the normal CML progression protein level. These methods are also applicable to imatinib resistance genes and/or proteins.
• The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising nucleic acid of at least one specific CML progression gene or an antibody that binds a CML progression/target protein or an IM resistance protein described herein, which may be conveniently used, e.g., in clinical settings, to diagnose patients exhibiting CML progression/target protein related disorder or abnormalities or exhibiting IM resistance.
• For the detection of mutations in a CML progression/target gene or an IM resistance gene, any nucleated cell can be used as a starting source for genomic nucleic acid, e.g., bone marrow or peripheral blood. For the detection of expression of a CML progression/target gene or an IM resistance gene or CML progression/target gene or IM resistance gene products, any cell type or tissue in which the CML progression/target gene or the IM resistance gene is expressed may be utilized.
• Nucleic acid-based detection techniques and peptide detection techniques are described in Section 5.3., infra. In one embodiment, the expression levels of one or more marker genes are measured using qRT-PCR.
5.2.3. Methods of Detecting CML Cells
• The invention also provides diagnostic methods for the detection of CML cells, e.g., advanced phase CML hematopoetic stem cells and/or immature myeloid cells, by detecting a cell surface expressed CML progression protein (e.g., PRAME or CD47) or conserved variants or peptide fragments thereof, using, for example, immunoassays wherein the CML progression protein or conserved variants or peptide fragments are detected by their interaction with an anti-CML progression protein antibody.
• For example, antibodies, or fragments of antibodies, such as those described in the present invention may be used to quantitatively or qualitatively detect advanced phase CML hematopoetic stem cells and/or immature myeloid cells by the presence of a CML progression protein or conserved variants or peptide fragments thereof on their surfaces. This can be accomplished, for example, by immunofluorescence techniques employing a fluorescently labeled antibody (see below, this Section) coupled with light microscopic, flow cytometric, or fluorimetric detection.
• The antibodies (or fragments thereof) useful in the present invention may, additionally, be employed histologically, as in immunofluorescence or immunoelectron microscopy, for in situ detection of a CML progression protein or conserved variants or peptide fragments thereof. In situ detection may be accomplished by removing a histological specimen from a patient, e.g., bone marrow, and applying thereto a labeled antibody of the present invention. The antibody (or fragment) is preferably applied by overlaying the labeled antibody (or fragment) onto a biological sample. Through the use of such a procedure, it is possible to determine not only the presence of the CML progression protein, or conserved variants or peptide fragments, but also its distribution in the examined tissue. Using the present invention, those of ordinary skill will readily perceive that any of a wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection.
• Immunoassays for a CML progression protein or conserved variants or peptide fragments thereof will typically comprise incubating a sample, such as a biological fluid, a tissue extract, freshly harvested cells, or lysates of cells which have been incubated in cell culture, in the presence of a detectably labeled antibody capable of identifying A CML progression protein or conserved variants or peptide fragments thereof, and detecting the bound antibody by any of a number of techniques well-known in the art.
• The biological sample may be brought in contact with and immobilized onto a solid phase support or carrier such as nitrocellulose, or other solid support which is capable of immobilizing cells, cell particles or soluble proteins. The support may then be washed with suitable buffers followed by treatment with the detectably labeled antibody specific for a CML progression protein. The solid phase support may then be washed with the buffer a second time to remove unbound antibody. The amount of bound label on solid support may then be detected by conventional means.
• By “solid phase support or carrier” is intended any support capable of binding an antigen or an antibody. Well-known supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the support configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tub, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, test strip, etc. Preferred supports include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation.
• The binding activity of a given lot of an antibody may be determined according to well-known methods. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation.
• One of the ways in which the antibody specific to a CML progression protein can be detectably labeled is by linking the same to an enzyme and use in an enzyme immunoassay (EIA) (Voller, A., “The Enzyme Linked Immunosorbent Assay (ELISA)”, 1978, Diagnostic Horizons 2:1-7, Microbiological Associates Quarterly Publication, Walkersville, Md.); Voller, A. et al., 1978, J. Clin. Pathol. 31:507-520; Butler, J. E., 1981, Meth. Enzymol. 73:482-523; Maggio, E. (ed.), 1980, Enzyme Immunoassay, CRC Press, Boca Raton, Fla.,; Ishikawa, E. et al., (eds.), 1981, Enzyme Immunoassay, Kgaku Shoin, Tokyo). The enzyme which is bound to the antibody will react with an appropriate substrate, preferably a chromogenic substrate, in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorimetric or by visual means. Enzymes which can be used to detectably label the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate, dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. The detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards.
• Detection may also be accomplished using any of a variety of other immunoassays. For example, by radioactively labeling the antibodies or antibody fragments, it is possible to detect a CML progression protein through the use of a radioimmunoassay (RIA) (see, for example, Weintraub, B., Principles of Radioimmunoassays, Seventh Training Course on Radioligand Assay Techniques, The Endocrine Society, March, 1986, which is incorporated by reference herein). The radioactive isotope can be detected by such means as the use of a gamma counter or a scintillation counter or by autoradiography.
• It is also possible to label the antibody with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wave length, its presence can then be detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine.
• The antibody can also be detectably labeled using fluorescence emitting metals such as¹⁵²Eu, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriaminepentacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).
• The antibody also can be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.
• Likewise, a bioluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in, which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence of a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aequorin.
• An antibody that is specific to a CML progression protein conjugated to detectable substances can be utilized to sort advanced phase CML cells from normal cells by methods known to those of skill in the art. In one embodiment, the advanced phase CML cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.
• In one embodiment, cells, e.g, cells in bone marrow or peripheral blood, obtained from a patient, e.g., a human, are incubated with fluorescently labeled antibody specific for the CML progression protein for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with the antibody, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the CML progression protein-specific antibody. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation and further characterization.
5.2.4. Sample Collection
• In the present invention, gene products, such as target polynucleotide molecules or proteins, are extracted from a sample taken from a CML patient. The sample may be collected in any clinically acceptable manner, but must be collected such that marker-derived polynucleotides (i.e., RNA) are preserved (if gene expression is to be measured) or proteins are preserved (if encoded proteins are to be measured). In one embodiment, bone marrow samples are used. In another embodiment, peripheral blood samples are used. In one embodiment, the pre-treatment bone marrow or peripheral blood sample from a patient is used. In another embodiment, the treatment bone marrow or peripheral blood sample from a patient after and/or during treatment is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a patient is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a clinical chronic phase patient is used. In another embodiment, the sorted bone marrow or peripheral blood sample from a patient after and/or during treatment is used. Other suitable samples may comprise any clinically relevant tissue sample, such as a tumor biopsy or fine needle aspirate, or a sample of body fluid, such as blood, plasma, serum, lymph, ascitic fluid, cystic fluid, or urine. The sample may be taken from a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines.
• In a specific embodiment, mRNA or nucleic acids derived therefrom (i.e., cDNA or amplified RNA or amplified DNA) are preferably labeled distinguishably from polynucleotide molecules of a reference sample, and both are simultaneously or independently hybridized to a microarray comprising some or all of the markers or marker sets or subsets described above. Alternatively, mRNA or nucleic acids derived therefrom may be labeled with the same label as the reference polynucleotide molecules, wherein the intensity of hybridization of each at a particular probe is compared.
• Methods for preparing total and poly(A)+ RNA are well known and are described generally in Sambrook et al., MOLECULARCLONING—A LABORATORYMANUAL(2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) and Ausubel et al., CURRENTPROTOCOLS INMOLECULARBIOLOGY, vol. 2, Current Protocols Publishing, New York (1994)). Preferably, total RNA, or total mRNA (poly(A)+ RNA) is measured in the methods of the invention directly or indirectly (e.g., via measuring cDNA or cRNA).
• RNA may be isolated from eukaryotic cells by procedures that involve lysis of the cells and denaturation of the proteins contained therein. Cells of interest include wild-type cells (i.e., non-cancerous), drug-exposed wild-type cells, tumor- or tumor-derived cells, modified cells, normal or tumor cell line cells, and drug-exposed modified cells. Preferably, the cells are breast cancer tumor cells.
• Additional steps may be employed to remove DNA. Cell lysis may be accomplished with a nonionic detergent, followed by microcentrifugation to remove the nuclei and hence the bulk of the cellular DNA. In one embodiment, RNA is extracted from cells of the various types of interest using guanidinium thiocyanate lysis followed by CsCl centrifugation to separate the RNA from DNA (Chirgwin et al.,Biochemistry18:5294-5299 (1979)). Poly(A)+ RNA is selected by selection with oligo-dT cellulose (see Sambrook et al., MOLECULARCLONING—A LABORATORYMANUAL(2NDED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). Alternatively, separation of RNA from DNA can be accomplished by organic extraction, for example, with hot phenol or phenol/chloroform/isoamyl alcohol.
• If desired, RNase inhibitors may be added to the lysis buffer. Likewise, for certain cell types, it may be desirable to add a protein denaturation/digestion step to the protocol.
• For many applications, it is desirable to preferentially enrich mRNA with respect to other cellular RNAs, such as transfer RNA (tRNA) and ribosomal RNA (rRNA). Most mRNAs contain a poly(A) tail at their 3′ end. This allows them to be enriched by affinity chromatography, for example, using oligo(dT) or poly(U) coupled to a solid support, such as cellulose or Sephadex™ (see Ausubel et al., CURRENTPROTOCOLS INMOLECULARBIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Once bound, poly(A)+ mRNA is eluted from the affinity column using 2 mM EDTA/0.1% SDS.
• In a specific embodiment, total RNA or total mRNA from cells is used in the methods of the invention. The source of the RNA can be cells of an animal, e.g., human, mammal, primate, non-human animal, dog, cat, mouse, rat, bird, etc. In specific embodiments, the method of the invention is used with a sample containing total mRNA or total RNA from 1×10⁶cells or less. In another embodiment, proteins can be isolated from the foregoing sources, by methods known in the art, for use in expression analysis at the protein level.
• Probes to the homologs of the marker sequences disclosed herein can be employed preferably when non-human nucleic acid is being assayed.
5.2.5. Determination of Abundance Levels of Gene Products
• The abundance levels of the gene products of the genes in a sample may be determined by any means known in the art. The levels may be determined by isolating and determining the level (i.e., amount) of nucleic acid transcribed from each marker gene. Alternatively, or additionally, the level of specific proteins encoded by a marker gene may be determined
• The levels of transcripts of specific marker genes can be accomplished by determining the amount of mRNA, or polynucleotides derived therefrom, present in a sample. Any method for determining RNA levels can be used. For example, RNA is isolated from a sample and separated on an agarose gel. The separated RNA is then transferred to a solid support, such as a filter. Nucleic acid probes representing one or more markers are then hybridized to the filter by northern hybridization, and the amount of marker-derived RNA is determined. Such determination can be visual, or machine-aided, for example, by use of a densitometer. Another method of determining RNA levels is by use of a dot-blot or a slot-blot. In this method, RNA, or nucleic acid derived therefrom, from a sample is labeled. The RNA or nucleic acid derived therefrom is then hybridized to a filter containing oligonucleotides derived from one or more marker genes, wherein the oligonucleotides are placed upon the filter at discrete, easily-identifiable locations. Hybridization, or lack thereof, of the labeled RNA to the filter-bound oligonucleotides is determined visually or by densitometer. Polynucleotides can be labeled using a radiolabel or a fluorescent (i.e., visible) label.
• The levels of transcripts of particular marker genes may also be assessed by determining the level of the specific protein expressed from the marker genes. This can be accomplished, for example, by separation of proteins from a sample on a polyacrylamide gel, followed by identification of specific marker-derived proteins using antibodies in a western blot. Alternatively, proteins can be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves isoelectric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al, 1990, GELELECTROPHORESIS OFPROTEINS: A PRACTICALAPPROACH, IRL Press, New York; Shevchenko et al.,Proc. Nat'l Acad. Sci. USA93:1440-1445 (1996); Sagliocco et al.,Yeast12:1519-1533 (1996); Lander,Science274:536-539 (1996). The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, western blotting and immunoblot analysis using polyclonal and monoclonal antibodies.
• Alternatively, marker-derived protein levels can be determined by constructing an antibody microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the marker-derived proteins of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, ANTIBODIES: A LABORATORYMANUAL, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array, and their binding is assayed with assays known in the art. Generally, the expression, and the level of expression, of proteins of diagnostic or prognostic interest can be detected through immunohistochemical staining of tissue slices or sections.
• Finally, levels of transcripts of marker genes in a number of tissue specimens may be characterized using a “tissue array” (Kononen et al.,Nat. Med.4(7):844-7 (1998)). In a tissue array, multiple tissue samples are assessed on the same microarray. The arrays allow in situ detection of RNA and protein levels; consecutive sections allow the analysis of multiple samples simultaneously.
5.2.5.1. Microarrays
• In preferred embodiments, polynucleotide microarrays are used to measure expression so that the expression status of each of the markers above is assessed simultaneously. Generally, microarrays according to the invention comprise a plurality of markers informative for clinical category determination, for a particular disease or condition.
• The invention also provides a microarray comprising for each of a plurality of genes, said genes being all or at least 5, 10, 20, 30, 40, 50, 70, 100 or 200 of the genes listed in Tables 1a and/or 1b or any of Tables 2a-2b, 4 and 5a-5b, or all or at least 5, 10, or 15 of the genes listed in Table 3, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 60%, 70%, 80%, 90%, 95%, or 98% of the probes on said microarray. In a particular embodiment, the invention provides such a microarray wherein the plurality of genes comprises the 20 genes listed in Table 3 or the 228 genes listed in Table 4 or the 368 genes listed in Tables 5a and 5b. The microarray can be in a sealed container.
• The microarrays preferably comprise at least 2, 3, 4, 5, 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, 200 or more of markers, or all of the markers, or any combination of markers, identified as informative for CML progression and/or imatinib resistance, e.g., within Tables 1a and 1b or any of Tables 2a-2b, 3, 4, and 5a-5b. The actual number of informative markers the microarray comprises will vary depending upon the particular condition of interest.
• In other embodiments, the invention provides polynucleotide arrays in which the CML progression markers comprise at least 50%, 60%, 70%, 80%, 85%, 90%, 95% or 98% of the probes on the array. In another specific embodiment, the microarray comprises a plurality of probes, wherein said plurality of probes comprise probes complementary and hybridizable to at least 75% of the CML progression markers.
• General methods pertaining to the construction of microarrays comprising the marker sets and/or subsets above are described in the following sections.
5.2.5.2. Construction of Microarrays
• Microarrays are prepared by selecting probes which comprise a polynucleotide sequence, and then immobilizing such probes to a solid support or surface. For example, the probes may comprise DNA sequences, RNA sequences, or copolymer sequences of DNA and RNA. The polynucleotide sequences of the probes may also comprise DNA and/or RNA analogues, or combinations thereof. For example, the polynucleotide sequences of the probes may be full or partial fragments of genomic DNA. The polynucleotide sequences of the probes may also be synthesized nucleotide sequences, such as synthetic oligonucleotide sequences. The probe sequences can be synthesized either enzymatically in vivo, enzymatically in vitro (e.g., by PCR), or non-enzymatically in vitro.
• The probe or probes used in the methods of the invention are preferably immobilized to a solid support which may be either porous or non-porous. For example, the probes may be polynucleotide sequences which are attached to a nitrocellulose or nylon membrane or filter covalently at either the 3′ or the 5′ end of the polynucleotide. Such hybridization probes are well known in the art (see, e.g., Sambrook et al., MOLECULARCLONING—A LABORATORYMANUAL(2NDED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). Alternatively, the solid support or surface may be a glass or plastic surface. In a particularly preferred embodiment, hybridization levels are measured to microarrays of probes consisting of a solid phase on the surface of which are immobilized a population of polynucleotides, such as a population of DNA or DNA mimics, or, alternatively, a population of RNA or RNA mimics. The solid phase may be a nonporous or, optionally, a porous material such as a gel.
• In preferred embodiments, a microarray comprises a support or surface with an ordered array of binding (e.g., hybridization) sites or “probes” each representing one of the markers described herein. Preferably the microarrays are addressable arrays, and more preferably positionally addressable arrays. More specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position in the array (i.e., on the support or surface). In preferred embodiments, each probe is covalently attached to the solid support at a single site.
• Microarrays can be made in a number of ways, of which several are described below. However produced, microarrays share certain characteristics. The arrays are reproducible, allowing multiple copies of a given array to be produced and easily compared with each other. Preferably, microarrays are made from materials that are stable under binding (e.g., nucleic acid hybridization) conditions. The microarrays are preferably small, e.g., between 1 cm²and 25 cm², between 12 cm²and 13 cm², or 3 cm². However, larger arrays are also contemplated and may be preferable, e.g., for use in screening arrays. Preferably, a given binding site or unique set of binding sites in the microarray will specifically bind (e.g., hybridize) to the product of a single gene in a cell (e.g., to a specific mRNA, or to a specific cDNA derived therefrom). However, in general, other related or similar sequences will cross hybridize to a given binding site.
• The microarrays of the present invention include one or more test probes, each of which has a polynucleotide sequence that is complementary to a subsequence of RNA or DNA to be detected. Preferably, the position of each probe on the solid surface is known. Indeed, the microarrays are preferably positionally addressable arrays. Specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position on the array (i.e., on the support or surface).
• According to the invention, the microarray is an array (i.e., a matrix) in which each position represents one of the markers described herein. For example, each position can contain a DNA or DNA analogue based on genomic DNA to which a particular RNA or cDNA transcribed from that genetic marker can specifically hybridize. The DNA or DNA analogue can be, e.g., a synthetic oligomer or a gene fragment. In one embodiment, probes representing each of the markers are present on the array. In a preferred embodiment, the array comprises probes for each of the markers listed in Tables 1a and/or 1b or any one of Tables 2a-2b, 3, 4, and 5a-5b.
5.2.5.3. Preparing Probes for Microarrays
• As noted above, the “probe” to which a particular polynucleotide molecule specifically hybridizes according to the invention contains a complementary genomic polynucleotide sequence. The probes of the microarray preferably consist of nucleotide sequences of no more than 1,000 nucleotides. In some embodiments, the probes of the array consist of nucleotide sequences of 10 to 1,000 nucleotides. In a preferred embodiment, the nucleotide sequences of the probes are in the range of 10-200 nucleotides in length and are genomic sequences of a species of organism, such that a plurality of different probes is present, with sequences complementary and thus capable of hybridizing to the genome of such a species of organism, sequentially tiled across all or a portion of such genome. In other specific embodiments, the probes are in the range of 10-30 nucleotides in length, in the range of 10-40 nucleotides in length, in the range of 20-50 nucleotides in length, in the range of 40-80 nucleotides in length, in the range of 50-150 nucleotides in length, in the range of 80-120 nucleotides in length, and most preferably are 60 nucleotides in length.
• The probes may comprise DNA or DNA “mimics” (e.g., derivatives and analogues) corresponding to a portion of an organism's genome. In another embodiment, the probes of the microarray are complementary RNA or RNA mimics. DNA mimics are polymers composed of subunits capable of specific, Watson-Crick-like hybridization with DNA, or of specific hybridization with RNA. The nucleic acids can be modified at the base moiety, at the sugar moiety, or at the phosphate backbone. Exemplary DNA mimics include, e.g., phosphorothioates.
• DNA can be obtained, e.g., by polymerase chain reaction (PCR) amplification of genomic DNA or cloned sequences. PCR primers are preferably chosen based on a known sequence of the genome that will result in amplification of specific fragments of genomic DNA. Computer programs that are well known in the art are useful in the design of primers with the required specificity and optimal amplification properties, such as Oligo version 5.0 (National Biosciences). Typically each probe on the microarray will be between 10 bases and 50,000 bases, usually between 300 bases and 1,000 bases in length. PCR methods are well known in the art, and are described, for example, in Innis et al., eds., PCR PROTOCOLS: A GUIDE TOMETHODS ANDAPPLICATIONS, Academic Press Inc., San Diego, Calif. (1990). It will be apparent to one skilled in the art that controlled robotic systems are useful for isolating and amplifying nucleic acids.
• An alternative, preferred means for generating the polynucleotide probes of the microarray is by synthesis of synthetic polynucleotides or oligonucleotides, e.g., using N-phosphonate or phosphoramidite chemistries (Froehler et al.,Nucleic Acid Res.14:5399-5407 (1986); McBride et al.,Tetrahedron Lett.24:246-248 (1983)). Synthetic sequences are typically between about 10 and about 500 bases in length, more typically between about 20 and about 100 bases, and most preferably between about 40 and about 70 bases in length. In some embodiments, synthetic nucleic acids include non-natural bases, such as, but by no means limited to, inosine. As noted above, nucleic acid analogues may be used as binding sites for hybridization. An example of a suitable nucleic acid analogue is peptide nucleic acid (see, e.g., Egholm et al.,Nature363:566-568 (1993); U.S. Pat. No. 5,539,083).
• Probes are preferably selected using an algorithm that takes into account binding energies, base composition, sequence complexity, cross-hybridization binding energies, and secondary structure. See Friend et al., International Patent Publication WO 01/05935, published Jan. 25, 2001; Hughes et al.,Nat. Biotech.19:342-7 (2001).
• A skilled artisan will also appreciate that positive control probes, e.g., probes known to be complementary and hybridizable to sequences in the target polynucleotide molecules, and negative control probes, e.g., probes known to not be complementary and hybridizable to sequences in the target polynucleotide molecules, should be included on the array. In one embodiment, positive controls are synthesized along the perimeter of the array. In another embodiment, positive controls are synthesized in diagonal stripes across the array. In still another embodiment, the reverse complement for each probe is synthesized next to the position of the probe to serve as a negative control. In yet another embodiment, sequences from other species of organism are used as negative controls or as “spike-in” controls.
5.2.5.4. Attaching Probes to the Solid Surface
• The probes are attached to a solid support or surface, which may be made, e.g., from glass, plastic (e.g., polypropylene, nylon), polyacrylamide, nitrocellulose, gel, or other porous or nonporous material. A preferred method for attaching the nucleic acids to a surface is by printing on glass plates, as is described generally by Schena et al,Science270:467-470 (1995). This method is especially useful for preparing microarrays of cDNA (See also, DeRisi et al,Nature Genetics14:457-460 (1996); Shalon et al.,Genome Res.6:639-645 (1996); and Schena et al.,Proc. Natl. Acad. Sci. U.S.A.93:10539-11286 (1995)).
• A second preferred method for making microarrays is by making high-density oligonucleotide arrays. Techniques are known for producing arrays containing thousands of oligonucleotides complementary to defined sequences, at defined locations on a surface using photolithographic techniques for synthesis in situ (see, Fodor et al., 1991,Science251:767-773; Pease et al., 1994, Proc. Natl. Acad. Sci. U.S.A.91:5022-5026; Lockhart et al., 1996, Nature Biotechnology14:1675; U.S. Pat. Nos. 5,578,832; 5,556,752; and 5,510,270) or other methods for rapid synthesis and deposition of defined oligonucleotides (Blanchard et al.,Biosensors&Bioelectronics11:687-690). When these methods are used, oligonucleotides (e.g., 60-mers) of known sequence are synthesized directly on a surface such as a derivatized glass slide. Usually, the array produced is redundant, with several oligonucleotide molecules per RNA.
• Other methods for making microarrays, e.g., by masking (Maskos and Southern, 1992, Nuc. Acids. Res.20:1679-1684), may also be used. In principle, and as noted supra, any type of array, for example, dot blots on a nylon hybridization membrane (see Sambrook et al., MOLECULARCLONING—A LABORATORYMANUAL(2NDED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) could be used. However, as will be recognized by those skilled in the art, very small arrays will frequently be preferred because hybridization volumes will be smaller.
• In one embodiment, the arrays of the present invention are prepared by synthesizing polynucleotide probes on a support. In such an embodiment, polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.
• In a particularly preferred embodiment, microarrays are manufactured by means of an ink jet printing device for oligonucleotide synthesis, e.g., using the methods and systems described by Blanchard in U.S. Pat. No. 6,028,189; Blanchard et al., 1996, Biosensors and Bioelectronics11:687-690; Blanchard, 1998, in Synthetic DNA Arrays in Genetic Engineering, Vol. 20, J. K. Setlow, Ed., Plenum Press, New York at pages 111-123. Specifically, the oligonucleotide probes in such microarrays are preferably synthesized in arrays, e.g., on a glass slide, by serially depositing individual nucleotide bases in “microdroplets” of a high surface tension solvent such as propylene carbonate. The microdroplets have small volumes (e.g., 100 pL or less, more preferably 50 pL or less) and are separated from each other on the microarray (e.g., by hydrophobic domains) to form circular surface tension wells which define the locations of the array elements (i.e., the different probes). Microarrays manufactured by this ink-jet method are typically of high density, preferably having a density of at least about 2,500 different probes per 1 cm². The polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.
5.2.5.5. Target Labeling and Hybridization to Microarrays
• The polynucleotide molecules which may be analyzed by the present invention (the “target polynucleotide molecules”) may be from any clinically relevant source, but are expressed RNA or a nucleic acid derived therefrom (e.g., cDNA or amplified RNA derived from cDNA that incorporates an RNA polymerase promoter), including naturally occurring nucleic acid molecules, as well as synthetic nucleic acid molecules. In one embodiment, the target polynucleotide molecules comprise RNA, including, but by no means limited to, total cellular RNA, poly(A)⁺ messenger RNA (mRNA) or fraction thereof, cytoplasmic mRNA, or RNA transcribed from cDNA (i.e., cRNA; see, e.g., Linsley & Schelter, U.S. patent application Ser. No. 09/411,074, filed Oct. 4, 1999, or U.S. Pat. Nos. 5,545,522, 5,891,636, or 5,716,785). Methods for preparing total and poly(A)⁺ RNA are well known in the art, and are described generally, e.g., in Sambrook et al., MOLECULARCLONING—A LABORATORYMANUAL(2NDED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). In one embodiment, RNA is extracted from cells of the various types of interest in this invention using guanidinium thiocyanate lysis followed by CsCl centrifugation (Chirgwin et al., 1979,Biochemistry18:5294-5299). In another embodiment, total RNA is extracted using a silica gel-based column, commercially available examples of which include RNeasy (Qiagen, Valencia, Calif.) and StrataPrep (Stratagene, La Jolla, Calif.). In an alternative embodiment, which is preferred forS. cerevisiae, RNA is extracted from cells using phenol and chloroform, as described in Ausubel et al., eds., 1989, CURRENTPROTOCOLS INMOLECULARBIOLOGY, Vol. III, Green Publishing Associates, Inc., John Wiley & Sons, Inc., New York, at pp. 13.12.1-13.12.5). Poly(A)⁺ RNA can be selected, e.g., by selection with oligo-dT cellulose or, alternatively, by oligo-dT primed reverse transcription of total cellular RNA. In one embodiment, RNA can be fragmented by methods known in the art, e.g., by incubation with ZnCl₂, to generate fragments of RNA. In another embodiment, the polynucleotide molecules analyzed by the invention comprise cDNA, or PCR products of amplified RNA or cDNA.
• In one embodiment, total RNA, mRNA, or nucleic acids derived therefrom, is isolated from a sample taken from a CML patient. Target polynucleotide molecules that are poorly expressed in particular cells may be enriched using normalization techniques (Bonaldo et al., 1996,Genome Res.6:791-806).
• As described above, the target polynucleotides are detectably labeled at one or more nucleotides. Any method known in the art may be used to detectably label the target polynucleotides. Preferably, this labeling incorporates the label uniformly along the length of the RNA, and more preferably, the labeling is carried out at a high degree of efficiency. One embodiment for this labeling uses oligo-dT primed reverse transcription to incorporate the label; however, conventional methods of this method are biased toward generating 3′ end fragments. Thus, in a preferred embodiment, random primers (e.g., 9-mers) are used in reverse transcription to uniformly incorporate labeled nucleotides over the full length of the target polynucleotides. Alternatively, random primers may be used in conjunction with PCR methods or T7 promoter-based in vitro transcription methods in order to amplify the target polynucleotides.
• In a preferred embodiment, the detectable label is a luminescent label. For example, fluorescent labels, bioluminescent labels, chemiluminescent labels, and colorimetric labels may be used in the present invention. In a highly preferred embodiment, the label is a fluorescent label, such as a fluorescein, a phosphor, a rhodamine, or a polymethine dye derivative. Examples of commercially available fluorescent labels include, for example, fluorescent phosphoramidites such as FluorePrime (Amersham Pharmacia, Piscataway, N.J.), Fluoredite (Millipore, Bedford, Mass.), FAM (ABI, Foster City, Calif.), and Cy3 or Cy5 (Amersham Pharmacia, Piscataway, N.J.). In another embodiment, the detectable label is a radiolabeled nucleotide.
• In a further preferred embodiment, target polynucleotide molecules from a patient sample are labeled differentially from target polynucleotide molecules of a reference sample. The reference can comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML) or from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.
• Nucleic acid hybridization and wash conditions are chosen so that the target polynucleotide molecules specifically bind or specifically hybridize to the complementary polynucleotide sequences of the array, preferably to a specific array site, wherein its complementary DNA is located.
• Arrays containing double-stranded probe DNA situated thereon are preferably subjected to denaturing conditions to render the DNA single-stranded prior to contacting with the target polynucleotide molecules. Arrays containing single-stranded probe DNA (e.g., synthetic oligodeoxyribonucleic acids) may need to be denatured prior to contacting with the target polynucleotide molecules, e.g., to remove hairpins or dimers which form due to self complementary sequences.
• Optimal hybridization conditions will depend on the length (e.g., oligomer versus polynucleotide greater than 200 bases) and type (e.g., RNA, or DNA) of probe and target nucleic acids. One of skill in the art will appreciate that as the oligonucleotides become shorter, it may become necessary to adjust their length to achieve a relatively uniform melting temperature for satisfactory hybridization results. General parameters for specific (i.e., stringent) hybridization conditions for nucleic acids are described in Sambrook et al., MOLECULARCLONING—A LABORATORYMANUAL(2NDED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989), and in Ausubel et al., CURRENTPROTOCOLS INMOLECULARBIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Typical hybridization conditions for the cDNA microarrays of Schena et al. are hybridization in 5×SSC plus 0.2% SDS at 65° C. for four hours, followed by washes at 25° C. in low stringency wash buffer (1×SSC plus 0.2% SDS), followed by 10 minutes at 25° C. in higher stringency wash buffer (0.1×SSC plus 0.2% SDS) (Schena et al.,Proc. Natl. Acad. Sci. U.S.A.93:10614 (1993)). Useful hybridization conditions are also provided in, e.g., Tijessen, 1993, HYBRIDIZATIONWITHNUCLEICACIDPROBES, Elsevier Science Publishers B. V.; and Kricka, 1992, NONISOTOPICDNA PROBETECHNIQUES, Academic Press, San Diego, Calif.
• Particularly preferred hybridization conditions include hybridization at a temperature at or near the mean melting temperature of the probes (e.g., within 51° C., more preferably within 21° C.) in 1 M NaCl, 50 mM MES buffer (pH 6.5), 0.5% sodium sarcosine and 30% formamide.
5.2.5.6. Signal Detection and Data Analysis
• When fluorescently labeled gene products are used, the fluorescence emissions at each site of a microarray may be, preferably, detected by scanning confocal laser microscopy. In one embodiment, a separate scan, using the appropriate excitation line, is carried out for each of the two fluorophores used. Alternatively, a laser may be used that allows simultaneous specimen illumination at wavelengths specific to the two fluorophores and emissions from the two fluorophores can be analyzed simultaneously (see Shalon et al., 1996, “A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization,”Genome Research6:639-645, which is incorporated by reference in its entirety for all purposes). In a preferred embodiment, the arrays are scanned with a laser fluorescent scanner with a computer controlled X-Y stage and a microscope objective. Sequential excitation of the two fluorophores is achieved with a multi-line, mixed gas laser and the emitted light is split by wavelength and detected with two photomultiplier tubes. Fluorescence laser scanning devices are described in Schena et al.,Genome Res.6:639-645 (1996), and in other references cited herein. Alternatively, the fiber-optic bundle described by Ferguson et al.,Nature Biotech.14:1681-1684 (1996), may be used to monitor mRNA abundance levels at a large number of sites simultaneously.
5.2.5.7. Other Assays for Detecting and Quantifying RNA
• In addition to microarrays such as those described above any technique known to one of skill for detecting and measuring RNA can be used in accordance with the methods of the invention. Non-limiting examples of techniques include Northern blotting, nuclease protection assays, RNA fingerprinting, polymerase chain reaction, ligase chain reaction, Qbeta replicase, isothermal amplification method, strand displacement amplification, transcription based amplification systems, nuclease protection (SI nuclease or RNAse protection assays), SAGE as well as methods disclosed in International Publication Nos. WO 88/10315 and WO 89/06700, and International Applications Nos. PCT/US87/00880 and PCT/US89/01025.
• A standard Northern blot assay can be used to ascertain an RNA transcript size, identify alternatively spliced RNA transcripts, and the relative amounts of mRNA in a sample, in accordance with conventional Northern hybridization techniques known to those persons of ordinary skill in the art. In Northern blots, RNA samples are first separated by size via electrophoresis in an agarose gel under denaturing conditions. The RNA is then transferred to a membrane, crosslinked and hybridized with a labeled probe. Nonisotopic or high specific activity radiolabeled probes can be used including random-primed, nick-translated, or PCR-generated DNA probes, in vitro transcribed RNA probes, and oligonucleotides. Additionally, sequences with only partial homology (e.g., cDNA from a different species or genomic DNA fragments that might contain an exon) may be used as probes. The labeled probe, e.g., a radiolabelled cDNA, either containing the full-length, single stranded DNA or a fragment of that DNA sequence may be at least 20, at least 30, at least 50, or at least 100 consecutive nucleotides in length. The probe can be labeled by any of the many different methods known to those skilled in this art. The labels most commonly employed for these studies are radioactive elements, enzymes, chemicals that fluoresce when exposed to ultraviolet light, and others. A number of fluorescent materials are known and can be utilized as labels. These include, but are not limited to, fluorescein, rhodamine, auramine, Texas Red, AMCA blue and Lucifer Yellow. A particular detecting material is anti-rabbit antibody prepared in goats and conjugated with fluorescein through an isothiocyanate. Proteins can also be labeled with a radioactive element or with an enzyme. The radioactive label can be detected by any of the currently available counting procedures. Non-limiting examples of isotopes include³H,¹⁴C,³²P,³⁵S,³⁶Cl,⁵¹Cr,⁵⁷Co,⁵⁸Co,⁵⁹Fe,⁹⁰Y,¹²⁵I,¹³¹I, and¹⁸⁶Re. Enzyme labels are likewise useful, and can be detected by any of the presently utilized colorimetric, spectrophotometric, fluorospectrophotometric, amperometric or gasometric techniques. The enzyme is conjugated to the selected particle by reaction with bridging molecules such as carbodiimides, diisocyanates, glutaraldehyde and the like. Any enzymes known to one of skill in the art can be utilized. Examples of such enzymes include, but are not limited to, peroxidase, beta-D-galactosidase, urease, glucose oxidase plus peroxidase and alkaline phosphatase. U.S. Pat. Nos. 3,654,090, 3,850,752, and 4,016,043 are referred to by way of example for their disclosure of alternate labeling material and methods.
• Nuclease protection assays (including both ribonuclease protection assays and S1 nuclease assays) can be used to detect and quantitate specific mRNAs. In nuclease protection assays, an antisense probe (labeled with, e.g., radiolabeled or nonisotopic) hybridizes in solution to an RNA sample. Following hybridization, single-stranded, unhybridized probe and RNA are degraded by nucleases. An acrylamide gel is used to separate the remaining protected fragments. Typically, solution hybridization is more efficient than membrane-based hybridization, and it can accommodate up to 100 μg of sample RNA, compared with the 20-30 μg maximum of blot hybridizations.
• The ribonuclease protection assay, which is the most common type of nuclease protection assay, requires the use of RNA probes. Oligonucleotides and other single-stranded DNA probes can only be used in assays containing S1 nuclease. The single-stranded, antisense probe must typically be completely homologous to target RNA to prevent cleavage of the probe:target hybrid by nuclease.
• Serial Analysis Gene Expression (SAGE), which is described in e.g., Velculescu et al., 1995, Science270:484-7; Carulli, et al., 1998, Journal of Cellular Biochemistry Supplements30/31:286-96, can also be used to determine RNA abundances in a cell sample.
• Quantitative reverse transcriptase PCR (qRT-PCR) can also be used to determine the expression profiles of marker genes (see, e.g., U.S. Patent Application Publication No. 2005/0048542A1). The first step in gene expression profiling by RT-PCR is the reverse transcription of the RNA template into cDNA, followed by its exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, Calif., USA), following the manufacturer's instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction.
• Although the PCR step can use a variety of thermostable DNA-dependent DNA polymerases, it typically employs the Taq DNA polymerase, which has a 5′-3′ nuclease activity but lacks a 3′-5′ proofreading endonuclease activity. Thus, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction. A third oligonucleotide, or probe, is designed to detect nucleotide sequence located between the two PCR primers. The probe is non-extendible by Taq DNA polymerase enzyme, and is labeled with a reporter fluorescent dye and a quencher fluorescent dye. Any laser-induced emission from the reporter dye is quenched by the quenching dye when the two dyes are located close together as they are on the probe. During the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data.
• TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, ABI PRISM 7700™. Sequence Detection System™ (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the 5′ nuclease procedure is run on a real-time quantitative PCR device such as the ABI PRISM 7700™ Sequence Detection System™. The system consists of a thermocycler, laser, charge-coupled device (CCD), camera and computer. The system includes software for running the instrument and for analyzing the data.
• 5′-Nuclease assay data are initially expressed as Ct, or the threshold cycle. Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The point when the fluorescent signal is first recorded as statistically significant is the threshold cycle (Ct).
• To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard is expressed at a constant level among different tissues, and is unaffected by the experimental treatment. RNAs most frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and β-actin.
• A more recent variation of the RT-PCR technique is the real time quantitative PCR, which measures PCR product accumulation through a dual-labeled fluorogenic probe (i.e., TaqMan® probe). Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).
5.2.5.8. Detection and Quantification of Protein
• Measurement of the translational state may be performed according to several methods. For example, whole genome monitoring of protein (e.g., the “proteome,”) can be carried out by constructing a microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the encoded proteins, or at least for those proteins relevant to the action of a drug of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, Antibodies: A Laboratory Manual, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array and their binding is assayed with assays known in the art.
• Immunoassays known to one of skill in the art can be used to detect and quantify protein levels. For example, ELISAs can be used to detect and quantify protein levels. ELISAs comprise preparing antigen, coating the well of a 96 well microtiter plate with the antigen, adding the antibody of interest conjugated to a detectable compound such as an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) to the well and incubating for a period of time, and detecting the presence of the antigen. In ELISAs the antibody of interest does not have to be conjugated to a detectable compound; instead, a second antibody (which recognizes the antibody of interest) conjugated to a detectable compound may be added to the well. Further, instead of coating the well with the antigen, the antibody may be coated to the well. In this case, a second antibody conjugated to a detectable compound may be added following the addition of the antigen of interest to the coated well. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected as well as other variations of ELISAs known in the art. In a preferred embodiment, an ELISA may be performed by coating a high binding 96-well microtiter plate (Costar) with 2 μg/ml of rhu-IL-9 in PBS overnight. Following three washes with PBS, the plate is incubated with three-fold serial dilutions of Fab at 25° C. for 1 hour. Following another three washes of PBS, 1 μg/ml anti-human kappa-alkaline phosphatase-conjugate is added and the plate is incubated for 1 hour at 25° C. Following three washes with PBST, the alkaline phosphatase activity is determined in 50 μl/AMP/PPMP substrate. The reactions are stopped and the absorbance at 560 nm is determined with a VMAX microplate reader. For further discussion regarding ELISAs see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 11.2.1.
• Protein levels may be determined by Western blot analysis. Further, protein levels as well as the phosphorylation of proteins can be determined by immunoprecitation followed by Western blot analysis Immunoprecipitation protocols generally comprise lysing a population of cells in a lysis buffer such as RIPA buffer (1% NP-40 or Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 0.15 M NaCl, 0.01 M sodium phosphate at pH 7.2, 1% Trasylol) supplemented with protein phosphatase and/or protease inhibitors (e.g., EDTA, PMSF, aprotinin, sodium vanadate), adding the antibody of interest to the cell lysate, incubating for a period of time (e.g., 1 to 4 hours) at 40° C., adding protein A and/or protein G sepharose beads to the cell lysate, incubating for about an hour or more at 40° C., washing the beads in lysis buffer and resuspending the beads in SDS/sample buffer. The ability of the antibody of interest to immunoprecipitate a particular antigen can be assessed by, e.g., western blot analysis. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the binding of the antibody to an antigen and decrease the background (e.g., pre-clearing the cell lysate with sepharose beads). For further discussion regarding immunoprecipitation protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.16.1.
• Western blot analysis generally comprises preparing protein samples, electrophoresis of the protein samples in a polyacrylamide gel (e.g., 8%-20% SDS-PAGE depending on the molecular weight of the antigen), transferring the protein sample from the polyacrylamide gel to a membrane such as nitrocellulose, PVDF or nylon, incubating the membrane in blocking solution (e.g., PBS with 3% BSA or non-fat milk), washing the membrane in washing buffer (e.g., PBS-Tween 20), incubating the membrane with primary antibody (the antibody of interest) diluted in blocking buffer, washing the membrane in washing buffer, incubating the membrane with a secondary antibody (which recognizes the primary antibody, e.g., an anti-human antibody) conjugated to an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) or radioactive molecule (e.g.,³²P or¹²⁵I) diluted in blocking buffer, washing the membrane in wash buffer, and detecting the presence of the antigen. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected and to reduce the background noise. For further discussion regarding western blot protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.8.1.
• Protein expression levels can also be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves iso-electric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al., 1990, Gel Electrophoresis of Proteins: A Practical Approach, IRL Press, New York; Shevchenko et al., 1996, Proc. Natl. Acad. Sci. USA93:1440-1445; Sagliocco et al., 1996, Yeast12:1519-1533; Lander, 1996, Science274:536-539. The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, Western blotting and immunoblot analysis using polyclonal and monoclonal antibodies, and internal and N-terminal micro-sequencing.
5.3. Treating CML by Modulating Expression and/or Activity of CML Progression Genes and/or their Products
• The invention provides methods and compositions for utilizing CML target genes listed in Table 3 or 5a or 5b and or imatinib resistance genes listed in Table 4 in treating CML. The methods and compositions are used for treating CML patient exhibiting aberrant regulation of one or more CML target/progression genes or IM resistance genes by modulating the expression and/or activity of such genes and/or the encoded proteins. The methods and composition can be used in conjunction with other CML treatment, e.g., imatinib mesylate. The compositions (e.g., agents that modulate expression and/or activity of the CML target gene or gene product) of the invention are preferably purified. In the following, for simplicity reasons, the methods are often described with reference to CML target gene(s). It will be understood that the methods are equally applicable to CML progression genes and IM resistance genes.
• In one embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene by reducing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.
• In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene as listed in Table 5a or 5b by reducing the expression and/or activity of the gene, and/or its encoded protein.
• In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene by enhancing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.
• In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene as listed in Table 5a or 5b by enhancing the expression and/or activity of the gene, and/or its encoded protein.
• In a specific embodiment, the invention provides a method for treating CML by administering to a patient (i) an agent that modulates the expression and/or activity of an imatinib resistance gene and/or the encoded protein, and (ii) a therapeutically sufficient amount of imatinib mesylate.
• In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting aberrant regulation of a plurality of different CML target gene as listed in Tables 5a and 5b by modulating the expression and/or activity of the plurality of genes, and/or its encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML progression gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins.
• A variety of therapeutic approaches may be used in accordance with the invention to modulate expression of a CML target gene or imatinib resistance gene and/or its encoded protein in vivo. For example, siRNA molecules may be engineered and used to silence a CML target gene in vivo. Antisense DNA molecules may also be engineered and used to block translation of a CML target mRNA in vivo. Alternatively, ribozyme molecules may be designed to cleave and destroy the mRNAs of a CML target gene in vivo. In another alternative, oligonucleotides designed to hybridize to the 5′ region of the CML target gene (including the region upstream of the coding sequence) and form triple helix structures may be used to block or reduce transcription of the CML target gene. The expression and/or activity of a CML target protein can be modulated using antibody, peptide or polypeptide molecules, and small organic or inorganic molecules. In the following, for simplicity, methods are described in reference to a CML target gene or protein. These methods are equally applicable to imatinib resistance genes.
• In a preferred embodiment, RNAi is used to knock down the expression of a CML target gene. In one embodiment, double-stranded RNA molecules of 21-23 nucleotides which hybridize to a homologous region of mRNAs transcribed from the CML target gene are used to degrade the mRNAs, thereby “silence” the expression of the CML target gene. The method can be used to reduce expression levels of aberrantly up-regulated CML target genes. Preferably, the dsRNAs have a hybridizing region, e.g., a 19-nucleotide double-stranded region, which is complementary to a sequence of the coding sequence of the CML target gene. Any siRNA that targets an appropriate coding sequence of a CML target gene and exhibit a sufficient level of silencing can be used in the invention. As exemplary embodiments, 21-nucleotide double-stranded siRNAs targeting the coding regions of a CML target gene are designed according to selection rules known in the art (see, e.g., Elbashir et al., 2002, Methods26:199-213; International Application No. PCT/US04/35636, filed Oct. 27, 2004, each of which is incorporated herein by reference in its entirety). In a preferred embodiment, the siRNA or siRNAs specifically inhibit the translation or transcription of a CML target protein without substantially affecting the translation or transcription of genes encoding other protein kinases in the same kinase family. In a specific embodiment, siRNAs targeting an up-regulated gene listed in Table 4 are used to silence the respective CML target genes.
• The invention also provides methods and compositions for treating a CML patient exhibiting aberrant up-regulation of a plurality of CML target genes as listed in Tables 5a and 5b by reducing the expression and/or activities of these genes, and/or their encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML target gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins. In a preferred embodiment, an siRNA is used to silence the plurality of different CML target genes. The sequence of the siRNA is chosen such that the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. Thus, when administrated to the patient, the siRNA silences all of the plurality of genes in cells of the patient. In preferred embodiments, the central contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 9-15, 9-12, 11, 10, or 9 nucleotides in length. The length and nucleotide base sequence of the target sequence of each different target gene, i.e., the sequence of the gene that is identical to an appropriate sense or antisense sequence of the siRNA, can be different from gene to gene. For example, gene A may have a sequence of 11 nucleotides identical to the nucleotide sequence 3-13 of the sense strand of the siRNA, while gene B may have a sequence of 12 nucleotides identical to the nucleotide sequence 4-15 of the sense strand of the siRNA. Thus, a single siRNA may be designed to silence a large number of CML target genes in cells.
• RNAi can be carried out using any standard method for introducing nucleic acids into cells. In one embodiment, gene silencing is induced by presenting the cell with one or more siRNAs targeting the CML target gene (see, e.g., Elbashir et al., 2001, Nature411, 494-498; Elbashir et al., 2001, Genes Dev.15, 188-200, all of which are incorporated by reference herein in their entirety). The siRNAs can be chemically synthesized, or derived from cleavage of double-stranded RNA by recombinant Dicer. Another method to introduce a double stranded DNA (dsRNA) for silencing of the CML target gene is shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev.16, 948-958; Brummelkamp et al., 2002, Science296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA99, 5515-5520, all of which are incorporated by reference herein in their entirety). In this method, a siRNA targeting a CML target gene is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid- or virus-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo (see, McCaffrey et al. 2002, Nature418, 38-39; Xia et al., 2002, Nat. Biotech.20, 1006-1010; Lewis et al., 2002, Nat. Genetics32, 107-108; Rubinson et al., 2003, Nat.Genetics33, 401-406; Tiscornia et al., 2003, Proc. Natl.Acad. Sci. USA100, 1844-1848, all of which are incorporated by reference herein in their entirety). Such plasmid- or virus-based shRNAs can be delivered using a gene therapy approach. SiRNAs targeting the CML target gene can also be delivered to an organ or tissue in a mammal, such a human, in vivo (see, e.g., Song et al. 2003, Nat.Medicine9, 347-351; Sorensen et al., 2003, J. Mol. Biol.327, 761-766; Lewis et al., 2002, Nat. Genetics32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the mammal The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the mammal
• In preferred embodiments, an siRNA pool (mixture) containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting a CML target gene at different sequence regions is used to silence the gene. In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually. As used herein, the word “about” with reference to concentration means within 20%. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has a concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene. In specific embodiments, a pool containing the 3 different is used for targeting a CML target gene. More detailed descriptions of techniques for carrying out RNAi are also presented in Section 5.6.
• In other embodiments, antisense, ribozyme, and triple helix forming nucleic acid are designed to inhibit the translation or transcription of a CML target protein or gene with minimal effects on the expression of other genes that may share one or more sequence motif with the CML target gene. To accomplish this, the oligonucleotides used should be designed on the basis of relevant sequences unique to a CML target gene. In one embodiment, the oligonucleotide used specifically inhibits the translation or transcription of a CML target protein or gene without substantially affecting the translation or transcription of other proteins in the same protein family.
• For example, and not by way of limitation, the oligonucleotides should not fall within those regions where the nucleotide sequence of a CML target gene is most homologous to that of other genes. In the case of antisense molecules, it is preferred that the sequence be at least 18 nucleotides in length in order to achieve sufficiently strong annealing to the target mRNA sequence to prevent translation of the sequence. Izant et al., 1984, Cell, 36:1007-1015; Rosenberg et al., 1985, Nature, 313:703-706.
• Ribozymes are RNA molecules which possess highly specific endoribonuclease activity. Hammerhead ribozymes comprise a hybridizing region which is complementary in nucleotide sequence to at least part of the target RNA, and a catalytic region which is adapted to cleave the target RNA. The hybridizing region contains nine (9) or more nucleotides. Therefore, the hammerhead ribozymes useful for targeting a CML target gene having a hybridizing region which is complementary to the sequences of the target gene and is at least nine nucleotides in length. The construction and production of such ribozymes is well known in the art and is described more fully in Haseloff et al., 1988, Nature, 334:585-591.
• The ribozymes of the present invention also include RNA endoribonucleases (hereinafter “Cech-type ribozymes”) such as the one which occurs naturally in Tetrahymena Thermophila (known as the IVS, or L-19 IVS RNA) and which has been extensively described by Thomas Cech and collaborators (Zaug, et al., 1984, Science, 224:574-578; Zaug and Cech, 1986, Science, 231:470-475; Zaug, et al., 1986, Nature, 324:429-433; published International patent application No. WO 88/04300 by University Patents Inc.; Been et al., 1986, Cell, 47:207-216). The Cech endoribonucleases have an eight base pair active site which hybridizes to a target RNA sequence whereafter cleavage of the target RNA takes place.
• In the case of oligonucleotides that hybridize to and form triple helix structures at the 5′ terminus of a CML target gene and can be used to block transcription, it is preferred that they be complementary to those sequences in the 5′ terminus of a CML target gene which are not present in other related genes. It is also preferred that the sequences not include those regions of the promoter of a CML target gene which are even slightly homologous to that of other related genes.
• The foregoing compounds can be administered by a variety of methods which are known in the art including, but not limited to the use of liposomes as a delivery vehicle. Naked DNA or RNA molecules may also be used where they are in a form which is resistant to degradation such as by modification of the ends, by the formation of circular molecules, or by the use of alternate bonds including phosphothionate and thiophosphoryl modified bonds. In addition, the delivery of nucleic acid may be by facilitated transport where the nucleic acid molecules are conjugated to poly-lysine or transferrin. Nucleic acid may also be transported into cells by any of the various viral carriers, including but not limited to, retrovirus, vaccinia, AAV, and adenovirus.
• Alternatively, a recombinant nucleic acid molecule which encodes, or is, such antisense nucleic acid, ribozyme, triple helix forming nucleic acid, or nucleic acid molecule of a CML target gene can be constructed. This nucleic acid molecule may be either RNA or DNA. If the nucleic acid encodes an RNA, it is preferred that the sequence be operatively attached to a regulatory element so that sufficient copies of the desired RNA product are produced. The regulatory element may permit either constitutive or regulated transcription of the sequence. In vivo, that is, within the cells or cells of an organism, a transfer vector such as a bacterial plasmid or viral RNA or DNA, encoding one or more of the RNAs, may be transfected into cells e.g. (Llewellyn et al., 1987, J. Mol. Biol., 195:115-123; Hanahan et al. 1983, J. Mol. Biol., 166:557-580). Once inside the cell, the transfer vector may replicate, and be transcribed by cellular polymerases to produce the RNA or it may be integrated into the genome of the host cell. Alternatively, a transfer vector containing sequences encoding one or more of the RNAs may be transfected into cells or introduced into cells by way of micromanipulation techniques such as microinjection, such that the transfer vector or a part thereof becomes integrated into the genome of the host cell.
• The activity of a CML target protein can be modulated by modulating the interaction of a CML target protein with its binding partners. In one embodiment, agents, e.g., antibodies, peptides, aptamers, small organic or inorganic molecules, can be used to inhibit binding of a CML target protein binding partner to treat CML. In another embodiment, agents, e.g., antibodies, aptamers, small organic or inorganic molecules, can be used to inhibit the activity of a CML target protein to treat CML.
• In other embodiments, when the CML target protein is a kinase, the invention provides small molecule inhibitors of the CML target protein. A small molecule inhibitor is a low molecular weight phosphorylation inhibitor. As used herein, a small molecule refers to an organic or inorganic molecule having a molecular weight is under 1000 Daltons, preferably in the range between 300 to 700 Daltons, which is not a nucleic acid molecule or a peptide molecule. The small molecule can be naturally occurring, e.g., extracted from plant or microorganisms, or non-naturally occurring, e.g., generated de novo by synthesis. A small molecule that is an inhibitor can be used to block a cellular process that dependent on a CML target protein. In one embodiment, the inhibitors are substrate mimics. In a preferred embodiment, the inhibitor of the CML target proteins is an ATP mimic. In one embodiment, such ATP mimics possess at least two aromatic rings. In a preferred embodiment, the ATP mimic comprises a moiety that forms extensive contacts with residues lining the ATP binding cleft of the CML target protein and/or peptide segments just outside the cleft, thereby selectively blocking the ATP binding site of the CML target protein. Minor structural differences from ATP can be introduced into the ATP mimic based on the peptide segments just outside the cleft. Such differences can lead to specific hydrogen bonding and hydrophobic interactions with the peptide segments just outside the cleft.
• In still other embodiments, antibodies that specifically bind the CML target protein are used. In a preferred embodiment, the invention provides antibodies that specifically bind the extracellular domain of a CML target protein that is a receptor. Antibodies that specifically bind a target can be obtained using standard method known in the art, e.g., a method described in Section 5.8.
• In one embodiment, an antibody-drug conjugate comprising an antibody that specifically binds a CML target protein is used. The efficacy of the antibodies that targets specific molecules expressed by advanced phase immature myeloid cells can be increased by attaching toxins to them. Existing immunotoxins are based on bacterial toxins like pseudomonas exotoxin, plant exotoxin like ricin or radio-nucleotides. The toxins are chemically conjugated to a specific ligand such as the variable domain of the heavy or light chain of the monoclonal antibody. Normal cells lacking the cancer specific antigens are not targeted by the targeted antibody. In a preferred embodiment, the CML target protein target is PRAME.
• In other embodiments, a peptide and peptidomimetic that interferes with the interaction of a CML target protein with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a peptide or peptidomimetic that interferes with substrate binding of a CML target protein is used. In another embodiment, peptide or peptidomimetic that interferes with the binding of a signal molecule to a CML target protein is used. In some embodiments of the invention, a fragment or polypeptide of at least 5, 10, 20, 50, 100 amino acids in length of a CML target protein are used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by standard method known in the art.
• In another embodiment, a dominant negative mutant of a CML target protein is used to reduce activity of a CML target protein. Such a dominant negative mutant can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a dominant negative mutant that interferes with substrate binding of a CML target protein is used. In another embodiment, a dominant negative mutant that interferes with the binding of a signal molecule to a CML target protein is used. In a preferred embodiment, the invention provides a dominant negative mutant that comprises the C-terminal region of a CML target protein. In another embodiment, the invention provides a dominant negative mutant that comprises the N-terminal region of the CML target protein.
• Gene therapy can be used for delivering any of the above described nucleic acid and protein/peptide therapeutics into target cells. Gene therapy is particularly useful for enhancing aberrantly down-regulated genes. Exemplary methods for carrying out gene therapy are described below. For general reviews of the methods of gene therapy, see Goldspiel et al., 1993, Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy 3:87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol. 32:573-596; Mulligan, 1993, Science 260:926-932; and Morgan and Anderson, 1993, Ann. Rev. Biochem. 62:191-217; May, 1993, TIBTECH 11(5):155-215). Methods commonly known in the art of recombinant DNA technology which can be used are described in Ausubel et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, New York; and Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, New York.
• In a preferred embodiment, the therapeutic comprises a nucleic acid that is part of an expression vector that expresses a the therapeutic nucleic acid or peptide/polypeptide in a suitable host. In particular, such a nucleic acid has a promoter operably linked to the coding region, said promoter being inducible or constitutive, and, optionally, tissue-specific. In another particular embodiment, a nucleic acid molecule is used in which the coding sequences and any other desired sequences are flanked by regions that promote homologous recombination at a desired site in the genome, thus providing for intrachromosomal expression of the CML target nucleic acid (see e.g., Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).
• Delivery of the nucleic acid into a patient may be either direct, in which case the patient is directly exposed to the nucleic acid or nucleic acid-carrying vector, or indirect, in which case, cells are first transformed with the nucleic acid in vitro, then transplanted into the patient. These two approaches are known, respectively, as in vivo or ex vivo gene therapy.
• In a specific embodiment, the nucleic acid is directly administered in vivo, where it is expressed to produce the encoded product. This can be accomplished by any of numerous methods known in the art, e.g., by constructing it as part of an appropriate nucleic acid expression vector and administering it so that it becomes intracellular, e.g., by infection using a defective or attenuated retroviral or other viral vector (see U.S. Pat. No. 4,980,286), or by direct injection of naked DNA, or by use of microparticle bombardment (e.g., a gene gun; Biolistic, Dupont), or coating with lipids or cell-surface receptors or transfecting agents, encapsulation in liposomes, microparticles, or microcapsules, or by administering it in linkage to a peptide which is known to enter the nucleus, by administering it in linkage to a ligand subject to receptor-mediated endocytosis (see e.g., Wu and Wu, 1987, J. Biol. Chem. 262:4429-4432) (which can be used to target cell types specifically expressing the receptors), etc. In another embodiment, a nucleic acid-ligand complex can be formed in which the ligand comprises a fusogenic viral peptide to disrupt endosomes, allowing the nucleic acid to avoid lysosomal degradation. In yet another embodiment, the nucleic acid can be targeted in vivo for cell specific uptake and expression, by targeting a specific receptor (see, e.g., PCT Publications WO 92/06180 dated Apr. 16, 1992 (Wu et al.); WO 92/22635 dated Dec. 23, 1992 (Wilson et al.); WO92/20316 dated Nov. 26, 1992 (Findeis et al.); WO93/14188 dated Jul. 22, 1993 (Clarke et al.), WO 93/20221 dated Oct. 14, 1993 (Young)). Alternatively, the nucleic acid can be introduced intracellularly and incorporated within host cell DNA for expression, by homologous recombination (Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).
• In a specific embodiment, a viral vector that contains the nucleic acid of a CML target gene is used. For example, a retroviral vector can be used (see Miller et al., 1993, Meth. Enzymol. 217:581-599). These retroviral vectors have been modified to delete retroviral sequences that are not necessary for packaging of the viral genome and integration into host cell DNA. The CML target nucleic acid to be used in gene therapy is cloned into the vector, which facilitates delivery of the gene into a patient. More detail about retroviral vectors can be found in Boesen et al., 1994, Biotherapy 6:291-302, which describes the use of a retroviral vector to deliver the mdr1 gene to hematopoietic stem cells in order to make the stem cells more resistant to chemotherapy. Other references illustrating the use of retroviral vectors in gene therapy are: Clowes et al., 1994, J. Clin. Invest. 93:644-651; Kiem et al., 1994, Blood 83:1467-1473; Salmons and Gunzberg, 1993, Human Gene Therapy 4:129-141; and Grossman and Wilson, 1993, Curr. Opin. Genet. and Devel. 3:110-114.
• Adenoviruses are other viral vectors that can be used in gene therapy. Adenoviruses are especially attractive vehicles for delivering genes to respiratory epithelia. Adenoviruses naturally infect respiratory epithelia where they cause a mild disease. Other targets for adenovirus-based delivery systems are liver, the central nervous system, endothelial cells, and muscle. Adenoviruses have the advantage of being capable of infecting non-dividing cells. Kozarsky and Wilson (1993, Current Opinion in Genetics and Development 3:499-503) present a review of adenovirus-based gene therapy. Bout et al. (1994, Human Gene Therapy 5:3-10) demonstrated the use of adenovirus vectors to transfer genes to the respiratory epithelia of rhesus monkeys. Other instances of the use of adenoviruses in gene therapy can be found in Rosenfeld et al., 1991, Science 252:431-434; Rosenfeld et al., 1992, Cell 68:143-155; and Mastrangeli et al., 1993, J. Clin. Invest. 91:225-234.
• Adeno-associated virus (AAV) has also been proposed for use in gene therapy (Walsh et al., 1993, Proc. Soc. Exp. Biol. Med. 204:289-300).
• Another approach to gene therapy involves transferring a gene to cells in tissue culture by such methods as electroporation, lipofection, calcium phosphate mediated transfection, or viral infection. Usually, the method of transfer includes the transfer of a selectable marker to the cells. The cells are then placed under selection to isolate those cells that have taken up and are expressing the transferred gene. Those cells are then delivered to a patient.
• In this embodiment, the nucleic acid is introduced into a cell prior to administration in vivo of the resulting recombinant cell. Such introduction can be carried out by any method known in the art, including but not limited to transfection, electroporation, microinjection, infection with a viral or bacteriophage vector containing the nucleic acid sequences, cell fusion, chromosome-mediated gene transfer, microcell-mediated gene transfer, spheroplast fusion, etc. Numerous techniques are known in the art for the introduction of foreign genes into cells (see e.g., Loeffler and Behr, 1993, Meth. Enzymol. 217:599-618; Cohen et al., 1993, Meth. Enzymol. 217:618-644; Cline, 1985, Pharmac. Ther. 29:69-92) and may be used in accordance with the present invention, provided that the necessary developmental and physiological functions of the recipient cells are not disrupted. The technique should provide for the stable transfer of the nucleic acid to the cell, so that the nucleic acid is expressible by the cell and preferably heritable and expressible by its cell progeny.
• The resulting recombinant cells can be delivered to a patient by various methods known in the art. In a preferred embodiment, epithelial cells are injected, e.g., subcutaneously. In another embodiment, recombinant skin cells may be applied as a skin graft onto the patient. Recombinant blood cells (e.g., hematopoietic stem or progenitor cells) are preferably administered intravenously. The amount of cells envisioned for use depends on the desired effect, patient state, etc., and can be determined by one skilled person in the art.
• Cells into which a nucleic acid can be introduced for purposes of gene therapy encompass any desired, available cell type, and include but are not limited to epithelial cells, endothelial cells, keratinocytes, fibroblasts, muscle cells, hepatocytes; blood cells such as T lymphocytes, B lymphocytes, monocytes, macrophages, neutrophils, eosinophils, megakaryocytes, granulocytes; various stem or progenitor cells, in particular hematopoietic stem or progenitor cells, e.g., as obtained from bone marrow, umbilical cord blood, peripheral blood, fetal liver, etc.
• In a preferred embodiment, the cell used for gene therapy is autologous to the patient.
• In an embodiment in which recombinant cells are used in gene therapy, a nucleic acid is introduced into the cells such that it is expressible by the cells or their progeny, and the recombinant cells are then administered in vivo for therapeutic effect. In a specific embodiment, stem or progenitor cells are used. Such stem cells can be hematopoietic stem cells (HSC).
• Any technique which provides for the isolation, propagation, and maintenance in vitro of HSC can be used in this embodiment of the invention. Techniques by which this may be accomplished include (a) the isolation and establishment of HSC cultures from bone marrow cells isolated from the future host, or a donor, or (b) the use of previously established long-term HSC cultures, which may be allogeneic or xenogeneic. Non-autologous HSC are used preferably in conjunction with a method of suppressing transplantation immune reactions of the future host/patient. In a particular embodiment of the present invention, human bone marrow cells can be obtained from the posterior iliac crest by needle aspiration (see e.g., Kodo et al., 1984, J. Clin. Invest. 73:1377-1384). The HSCs can be made highly enriched or in substantially pure form. This enrichment can be accomplished before, during, or after long-term culturing, and can be done by any techniques known in the art. Long-term cultures of bone marrow cells can be established and maintained by using, for example, modified Dexter cell culture techniques (Dexter et al., 1977, J. Cell Physiol. 91:335) or Witlock-Witte culture techniques (Witlock and Witte, 1982, Proc. Natl. Acad. Sci. U.S.A. 79:3608-3612).
• In a specific embodiment, the nucleic acid to be introduced for purposes of gene therapy comprises an inducible promoter operably linked to the coding region, such that expression of the nucleic acid is controllable by controlling the presence or absence of the appropriate inducer of transcription.
• The methods and/or compositions described above for modulating the expression and/or activity of a CML target gene or CML target protein may be used to treat patients in conjunction with a chemotherapeutic agent, e.g., Gleevec™
• The effects or benefits of administration of the compositions of the invention alone or in conjunction with a chemotherapeutic agent can be evaluated by any methods known in the art, e.g., by methods that are based on measuring the survival rate, side effects, dosage requirement of the chemotherapeutic agent, or any combinations thereof. If the administration of the compositions of the invention achieves any one or more benefits in a patient, such as increasing the survival rate, decreasing side effects, lowing the dosage requirement for the chemotherapeutic agent, the compositions of the invention are said to have augmented a chemotherapy, and the method is said to have efficacy.
5.4. Diagnosis and Treatment of CML by Targeting Cell Surface Expressed PRAME
• The present invention provides methods and compositions for diagnosis and treatment of CML by targeting PRAME (GenBank® accession no. NM_—006115) on cell surfaces of advanced phase hematopoetic stem cells and immature myeloid cells. PRAME is known to be expressed in testis and to expressed at a low level in endometrium, adrenals and ovaries, and is not expressed in other normal tissues. The inventors have found that PRAME is significantly overexpressed in advanced phase CML cells as compared to chronic phase CML cells. Thus, methods and compositions that target PRAME can be used for detecting advanced phase CML cells and for treating CML by selectively targeting advanced phase CML cells.
5.4.1. Methods of Detecting Advanced Phase CML
• Antibodies or labeled antibodies directed against a PRAME (Preferentially Expressed Antigen of Melanoma) can be used for evaluating CML progression, e.g., by detecting the presence of PRAME protein on cell surface of hematopoetic stem cells and immature myeloid cells. Such diagnostic/prognostic methods are particularly useful for detecting CML progression in unsorted samples.
• The tissue or cell type to be analyzed may include those which are known to relate to CML, e.g., bone marrow or peripheral blood. The protein isolation methods employed herein may, for example, be such as those described in Harlow and Lane (Harlow, E. and Lane, D., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.), which is incorporated herein by reference in its entirety. The isolated cells can be derived from cell culture or from a patient. The analysis of cells taken from culture may be a necessary step in the assessment of cells to be used as part of a cell-based gene therapy technique or, alternatively, to test the effect of compounds for CML treatment.
• In one embodiment, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein conjugated with a label; and (b) detecting said label in said sample, wherein detection of said label above a predetermined threshold indicating said patient has advanced phase CML. Detection of the labeled antibody can be performed using a method described in Section 5.2.5, supra.
5.4.2. Methods of Treating CML by Targeting PRAME
• The invention provides methods and compositions for treating CML by targeting PRAME expressed on the cell surface.
• In one embodiment, the present invention provides methods of using anti-PRAME antibodies for treatment of a CML patient. In the methods of the invention, one or more anti-PRAME antibodies are administered to the patient. The anti-PRAME antibodies bind to PRAME on the surface of advanced phase CML hematopoetic stem cells and/or immature myeloid cells. The binding of anti-PRAME antibodies to PRAME blocks the function mediated by PRAME, thereby preventing the proliferation of advanced phase hematopoetic stem cells.
• In another embodiment, the present invention provides a method for treatment of CML using an anti-PRAME antibody that belongs to an isotype that is capable of mediating lysis of cells to which the anti-PRAME antibody is bound. In a preferred embodiment, the anti-PRAME antibody belongs to an isotype that binds a growth factor receptor and activates serum complement and/or mediates antibody dependent cellular cytotoxicity (ADCC) by activating effector cells, e.g., macrophages. In another preferred embodiment, the isotype is IgG1, IgG2a, IgG3 or IgM.
• In still another embodiment, the anti-PRAME antibodies are used in conjunction with one or more other chemotherapeutic drugs. In such combined therapies, the anti-PRAME antibodies can be administered in a manner such as described in Section 5.10.5.
• The dosage of the anti-PRAME antibodies can be determined by routine experiments that are familiar to one skilled in the art. The effects or benefits of administration of the anti-PRAME antibodies can be evaluated by any method known in the art.
• In another embodiment, an antibody-drug conjugate comprising an antibody that specifically binds PRAME and a chemotherapeutic drug is used to selectively deliver the chemotherapeutic drug to advanced phase CML hematopoetic stem cells and/or immature myeloid cells. Chemotherapeutic drugs normally spread throughout the body, reaching not only the intended target but also healthy cells/organs such as the intestines and healthy bone marrow, where they kill off normal dividing cells. A drug conjugated to PRAME should be able to selectively target the advance phase CML hematopoetic stem cells and/or immature myeloid cells, thus increasing the sensitivity and specificity of the drug. For example, an anti-PRAME antibody may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion (see, e.g., Section 5.8). Any suitable antibody-drug conjugate, e.g., those described in Section 5.8.3 can be used. Normal hematopoetic stem cells and/or myeloid cells lack PRAME and are not targeted by the antibody.
• In still another embodiment, a peptide or a peptidomimetic that interferes with the interaction of PRAME with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of PRAME. In some embodiments of the invention, a PRAME fragment of at least 5, 10, 20, 50, 100 amino acids in length is used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by a standard method known in the art (see, e.g., Section 5.8.4).
• The invention also provides methods for treating CML using fragments of a PRAME protein as vaccines to elicit an immunotherapeutic response in a patient, e.g., an antibody response and/or a cell mediated immune response. Antibody responses involve the production of antibodies, which are proteins called immunoglobulins. The antibodies circulate in the bloodstream and permeate the other body fluids, where they bind specifically to the foreign antigen that elicited them. Binding by antibody inactivates advanced phase CML hematopoetic stem cells and/or immature myeloid cells by blocking their functions facilitated by PRAME. Antibody binding also marks advanced phase CML hematopoetic stem cells and/or immature myeloid cells, either by making it easier for a phagocytic cell to ingest them or by activating a system of blood proteins, collectively called complement, which kills the marked target cells.
• Cell-mediated immune responses to PRAME involve the production of specialized cells that react with PRAME antigen on the surface of advanced phase CML cells. T lymphocytes, which develop in the thymus, are responsible for cell-mediated immunity. The majority of T lymphocytes, called helper T cells and suppressor T cells, play a regulatory role in immunity, acting either to enhance or suppress the responses of other white blood cells. Other T lymphocytes, called cytotoxic T cells (CTLs), kill virus-infected cells, parasites, and cancer cells. The surface of T cells contains transmembrane proteins called T cell receptors that recognize the PRAME antigen on the surface of PRAME presenting advanced phase CML cells. T cell receptors are antibody-like proteins. The antigen must be presented to the T cell by a particular membrane protein, one encoded by a complex of genes called the major histocompatibility complex (MHC). Histocompatibility molecules are expressed on the cells of all higher vertebrates. There are two principal classes of MHC molecules, class I MHC and class II MHC. Cytotoxic T lymphocytes (CTLs) recognize foreign antigens in association with class I MHC glycoproteins on the surface of an antigen-presenting cell, whereas helper T cells recognize foreign antigens in association with class II MHC glycoproteins on the surface of an antigen-presenting cell. A cytotoxic T lymphocyte will kill an antigen-presenting cell when it recognizes antigen bound to class I MHC molecules on the surface of the antigen-presenting cell. In one embodiment, a PRAME vaccine is used to elicit production of CTLs.
• The PRAME protein fragment or polypeptide can be prepared by a standard method known in the art. In a specific embodiment, the fragment is a human PRAME protein fragment, or its murine homolog. In another embodiment, the vaccine comprises a peptide sequence that is at least 30%, 50%, 70%, 90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME protein, e.g., as determined by a BLAST algorithm. In some embodiments, the PRAME protein fragments or polypeptides are at least 5, 10, 20, 50, 100 amino acids in length.
• A peptide or polypeptide which is functionally equivalent to any PRAME fragment described above can also be used. Such an equivalent PRAME fragment may contain deletions, additions or substitutions of amino acid residues within the amino acid sequence encoded by the PRAME gene sequence but which result in a silent change, thus producing a functionally equivalent PRAME protein fragment. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. Conservative substitutions may be made from among amino acids of the same polarity. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. “Functionally equivalent”, as utilized herein, refers to a protein fragment capable of exhibiting a substantially similar in vivo activity as the endogenous PRAME protein fragment.
• The PRAME peptide fragments may be produced by recombinant DNA technology using techniques well known in the art (see, e.g., Section 5.8.4).
• The PRAME peptide can be used in combination with a suitable carrier and/or adjuvant, such as Freund's complete or incomplete adjuvant, or a similar immunostimulatory agent. An oil/surfactant based adjuvant comprising one or more surfactants combined with one or more non-metabolizable mineral oil or metabolizable oil, such as the Incomplete Seppic Adjuvant (Seppic, Paris, France), may be used. An Incomplete Seppic Adjuvant has a comparable effect as Incomplete Freund's Adjuvant for antibody production, but induces a lower inflammatory response.
• A fragment of a PRAME gene can also be used as a DNA or RNA vaccine. In a specific embodiment, the fragment of a PRAME gene is a fragment of a human PRAME gene, or its murine homolog. The invention also provides any sequence that is at least 30%, 50%_,70%_,90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME gene. In some embodiments of the invention, the fragment of a PRAME gene is at least 20, 25, 40, 60, 80, 100, 500, 1000 bases in length. Such sequences may be useful for production of PRAME peptides.
• In another embodiment, the present invention provides a naked DNA or RNA vaccine comprising a fragment of a PRAME gene, and uses thereof. The PRAME DNA fragment can be administered as a vaccine to elicit anti-PRAME antibodies. The DNA can be converted to RNA for example by subcloning the DNA into a transcriptional vector, such as pGEM family of plasmid vectors, or under control of a transcriptional promoter of a virus such as vaccinia, and the RNA used as a naked RNA vaccine. The naked DNA or RNA vaccine can be injected alone, or combined with one or more DNA or RNA vaccines directed to PRAME.
• The naked DNA or RNA vaccine of the present invention can be administered for example intramuscularly, or alternatively, can be used in nose drops. The DNA or RNA fragment or a portion thereof can be injected as naked DNA or RNA, as DNA or RNA encapsulated in liposomes, as DNA or RNA entrapped in proteoliposomes containing viral envelope receptor proteins (Nicolau, C. et al. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 1068; Kanoda, Y., et al. Science 1989, 243, 375; Mannino, R. J. et al. Biotechniques 1988, 6, 682). Alternatively, the DNA can be injected along with a carrier. A carrier can be a protein or such as a cytokine, forexample interleukin 2, or a polylysine-glycoprotein carrier (Wu, G. Y. and Wu, C. H. J. Biol. Chem. 1988, 263, 14621), or a nonreplicating vector, for example expression vectors containing either the Rous sarcoma virus or cytomegalovirus promoters. Such carrier proteins and vectors and methods for using same are known to a person in the art (See for example, Acsadi, G. et al. Nature 1991, 352, 815-818). In addition, the DNA or RNA could be coated onto tiny gold beads and the beads introduced into the skin with, for example, a gene gun (Cohen, J. Science 1993, 259, 1691-1692; Ulmer, J. B. et al. Science 1993, 259, 1745-1749).
5.4.3. Depletion of Advanced Phase CML Hematopoetic Stem Cells and/or Immature Myeloid Cells In Vitro
• The invention provides methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells from bone marrow or blood in vitro (or ex vivo). In particular, the invention provides for methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells by killing them or by separating them from bone marrow or blood. In one embodiment, anti-PRAME antibodies are combined, e.g., incubated, in vitro with bone marrow or blood from a patient, e.g., a human.
• In one embodiment, a column containing an anti-PRAME antibody bound to a solid matrix is used to remove advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or blood sample.
• The anti-PRAME antibodies used in the in vitro depletion of advanced phase CML hematopoetic stem cells and/or immature myeloid cells from samples can be conjugated to detectable labels (e.g., various enzymes, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials) or therapeutic agents (e.g., cytostatic and cytocidal agents), which are disclosed in section 5.8.3.
• Anti-PRAME antibodies conjugated to detectable substances can be utilized to sort advanced phase hematopoetic stem cells and/or immature myeloid cells from bone marrow or peripheral blood samples by methods known to those of skill in the art. In one embodiment, advanced phase hematopoetic stem cells and/or immature myeloid cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.
• In one embodiment, bone marrow or peripheral blood samples, obtained from a patient, e.g., a human, are incubated with fluorescently labeled PRAME specific antibodies for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with PRAME specific antibodies, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the PRAME specific antibodies. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation.
• In another embodiment, magnetic beads can be used to separate advanced phase immature myeloid cells from bone marrow or peripheral blood samples. Advanced phase immature myeloid cells may be sorted using a magnetic activated cell sorting (MACS) technique, a method for separating particles based on their ability to bind magnetic beads (0.5-100 nm diameter) (Dynal, 1995). A variety of useful modifications can be performed on the magnetic microspheres, including covalent addition of antibody which immunospecifically recognizes PRAME. A magnetic field is then applied, to physically manipulate the selected beads. The beads are then mixed with the cells to allow binding. Cells are then passed through a magnetic field to separate out advanced phase CML hematopoetic stem cells and/or immature myeloid cells.
• Bone marrow or peripheral blood sample from a patient that is depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be used for autologous transplant treatment of the patient. Healthy bone marrow or peripheral blood cells from a sample depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be collected. These cells can then be administered to the patient to replace the abnormal cells in the patient's bone marrow. Healthy bone marrow or peripheral blood cells can also be stored, e.g., frozen, for transplant at a later time.
5.5. Methods for Screening Agents that Modulate CML Progression/Target or IM Resistance Proteins
• Agents that modulate the expression or activity of a CML progression/target gene or encoded protein (or imatinib resistance gene or encoded protein), or modulate interaction of a CML progression/target protein (or imatinib resistance protein) with other proteins or molecules can be identified using a method described in this section. Such agents are useful in treating CML patients who exhibit aberrant regulation of these genes. In the following, for simplicity, methods directed to CML progression/target gene are described. These methods are equally applicable to imatinib resistance genes.
5.5.1. Screening Assays
• The following assays are designed to identify compounds that bind to a CML progression gene or its products, bind to other cellular proteins that interact with a CML progression protein, bind to cellular constituents, e.g., proteins, that are affected by a CML progression protein, or bind to compounds that interfere with the interaction of the CML progression gene or its product with other cellular proteins and to compounds which modulate the expression or activity of a CML progression gene (i.e., modulate the expression level of the CML progression gene and/or modulate the activity level of the CML progression protein). Assays may additionally be utilized which identify compounds which bind to CML progression protein regulatory sequences (e.g., promoter sequences), see e.g., Platt, K. A., 1994, J. Biol. Chem. 269:28558-28562, which is incorporated herein by reference in its entirety, which may modulate the level of CML progression gene expression. Compounds may include, but are not limited to, small organic molecules which are able to affect expression of the CML progression gene or some other gene involved in the CML progression protein pathways, or other cellular proteins. Further, among these compounds are compounds which affect the level of CML progression gene expression and/or CML progression protein activity and which can be used in the regulation of sensitivity to the effect of a chemotherapy agent.
• Compounds may include, but are not limited to, peptides such as, for example, soluble peptides, including but not limited to, Ig-tailed fusion peptides, and members of random peptide libraries (see, e.g., Lam, K. S. et al., 1991, Nature354:82-84; Houghten, R. et al., 1991, Nature 354:84-86), and combinatorial chemistry-derived molecular library made of D- and/or L-configuration amino acids, phosphopeptides (including, but not limited to members of random or partially degenerate, directed phosphopeptide libraries; see, e.g., Songyang, Z. et al., 1993, Cell 72:767-778), antibodies (including, but not limited to, polyclonal, monoclonal, humanized, anti-idiotypic, chimeric or single chain antibodies, and Fab, F(ab′)₂and Fab expression library fragments, and epitope-binding fragments thereof), and small organic or inorganic molecules.
• Compounds identified via assays such as those described herein may be useful, for example, in modulating the biological function of the CML progression protein.
• In vitro systems may be designed to identify compounds capable of binding a CML progression protein. Compounds identified may be useful, for example, in modulating the activity of wild type and/or mutant CML progression protein, may be useful in elaborating the biological function of the CML progression protein, may be utilized in screens for identifying compounds that disrupt normal CML progression protein interactions, or may in themselves disrupt such interactions.
• The principle of the assays used to identify compounds that bind to the CML progression protein involves preparing a reaction mixture of the CML progression protein and the test compound under conditions and for a time sufficient to allow the two components to interact and bind, thus forming a complex which can be removed and/or detected in the reaction mixture. These assays can be conducted in a variety of ways. For example, one method to conduct such an assay would involve anchoring CML progression protein or the test substance onto a solid phase and detecting CML progression protein/test compound complexes anchored on the solid phase at the end of the reaction. In one embodiment of such a method, the CML progression protein may be anchored onto a solid surface, and the test compound, which is not anchored, may be labeled, either directly or indirectly.
• In practice, microtiter plates may conveniently be utilized as the solid phase. The anchored component may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished by simply coating the solid surface with a solution of the protein and drying. Alternatively, an immobilized antibody, preferably a monoclonal antibody, specific for the protein to be immobilized may be used to anchor the protein to the solid surface. The surfaces may be prepared in advance and stored.
• In order to conduct the assay, the nonimmobilized component is added to the coated surface containing the anchored component. After the reaction is complete, unreacted components are removed (e.g., by washing) under conditions such that any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the previously nonimmobilized component is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the previously nonimmobilized component is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the previously nonimmobilized component (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody).
• Alternatively, a reaction can be conducted in a liquid phase, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for a CML progression protein or the test compound to anchor any complexes formed in solution, and a labeled antibody specific for the other component of the possible complex to detect anchored complexes.
• The CML progression gene or CML progression protein may interact in vivo with one or more intracellular or extracellular molecules, such as proteins. For purposes of this discussion, such molecules are referred to herein as “binding partners”. Compounds that disrupt CML progression protein binding may be useful in modulating the activity of the CML progression protein. Compounds that disrupt CML progression gene binding may be useful in modulating the expression of the CML progression gene, such as by modulating the binding of a regulator of CML progression gene. Such compounds may include, but are not limited to molecules such as peptides which would be capable of gaining access to the CML progression protein.
• The basic principle of the assay systems used to identify compounds that interfere with the interaction between the CML progression protein and its intracellular or extracellular binding partner or partners involves preparing a reaction mixture containing the CML progression protein, and the binding partner under conditions and for a time sufficient to allow the two to interact and bind, thus forming a complex. In order to test a compound for inhibitory activity, the reaction mixture is prepared in the presence and absence of the test compound. The test compound may be initially included in the reaction mixture, or may be added at a time subsequent to the addition of a CML progression protein and its binding partner. Control reaction mixtures are incubated without the test compound or with a placebo. The formation of any complexes between the CML progression protein and the binding partner is then detected. The formation of a complex in the control reaction, but not in the reaction mixture containing the test compound, indicates that the compound interferes with the interaction of the CML progression protein and the interactive binding partner. Additionally, complex formation within reaction mixtures containing the test compound and a normal CML progression protein may also be compared to complex formation within reaction mixtures containing the test compound and a mutant CML progression protein. This comparison may be important in those cases where it is desirable to identify compounds that disrupt interactions of mutant but not the normal CML progression protein.
• The assay for compounds that interfere with the interaction of the CML progression proteins and binding partners can be conducted in a heterogeneous or homogeneous format. Heterogeneous assays involve anchoring either the CML progression protein or the binding partner onto a solid phase and detecting complexes anchored on the solid phase at the end of the reaction. In homogeneous assays, the entire reaction is carried out in a liquid phase. In either approach, the order of addition of reactants can be varied to obtain different information about the compounds being tested. For example, test compounds that interfere with the interaction between the CML progression proteins and the binding partners, e.g., by competition, can be identified by conducting the reaction in the presence of the test substance; i.e., by adding the test substance to the reaction mixture prior to or simultaneously with the CML progression protein and interactive binding partner. Alternatively, test compounds that disrupt preformed complexes, e.g. compounds with higher binding constants that displace one of the components from the complex, can be tested by adding the test compound to the reaction mixture after complexes have been formed. The various formats are described briefly below.
• In a heterogeneous assay system, either the CML progression protein or its interactive binding partner, is anchored onto a solid surface, while the non-anchored species is labeled, either directly or indirectly. In practice, microtiter plates are conveniently utilized. The anchored species may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished simply by coating the solid surface with a solution of the CML progression protein or binding partner and drying. Alternatively, an immobilized antibody specific for the species to be anchored may be used to anchor the species to the solid surface. The surfaces may be prepared in advance and stored.
• In order to conduct the assay, the partner of the immobilized species is exposed to the coated surface with or without the test compound. After the reaction is complete, unreacted components are removed (e.g., by washing) and any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the non-immobilized species is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the non-immobilized species is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the initially non-immobilized species (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody). Depending upon the order of addition of reaction components, test compounds which inhibit complex formation or which disrupt preformed complexes can be detected.
• Alternatively, the reaction can be conducted in a liquid phase in the presence or absence of the test compound, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for one of the binding components to anchor any complexes formed in solution, and a labeled antibody specific for the other partner to detect anchored complexes. Again, depending upon the order of addition of reactants to the liquid phase, test compounds which inhibit complex or which disrupt preformed complexes can be identified.
• In an alternative embodiment of the invention, a homogeneous assay can be used. In this approach, a preformed complex of the CML progression protein and the interactive binding partner is prepared in which either the CML progression protein or its binding partners is labeled, but the signal generated by the label is quenched due to complex formation (see, e.g., U.S. Pat. No. 4,109,496 which utilizes this approach for immunoassays). The addition of a test substance that competes with and displaces one of the species from the preformed complex will result in the generation of a signal above background. In this way, test substances which disrupt CML progression protein/binding partner interaction can be identified.
• In a particular embodiment, the CML progression protein can be prepared for immobilization using recombinant DNA techniques. For example, the coding region of CML progression gene can be fused to a glutathione-S-transferase (GST) gene using a fusion vector, such as pGEX-5X-1, in such a manner that its binding activity is maintained in the resulting fusion protein. The interactive binding partner can be purified and used to raise a monoclonal antibody, using methods routinely practiced in the art. This antibody can be labeled with the radioactive isotope¹²⁵I, for example, by methods routinely practiced in the art. In a heterogeneous assay, e.g., the GST-CML progression protein fusion protein can be anchored to glutathione-agarose beads. The interactive binding partner can then be added in the presence or absence of the test compound in a manner that allows interaction and binding to occur. At the end of the reaction period, unbound material can be washed away, and the labeled monoclonal antibody can be added to the system and allowed to bind to the complexed components. The interaction between the CML progression protein and the interactive binding partner can be detected by measuring the amount of radioactivity that remains associated with the glutathione-agarose beads. A successful inhibition of the interaction by the test compound will result in a decrease in measured radioactivity.
• Alternatively, the GST-CML progression protein fusion protein and the interactive binding partner can be mixed together in liquid in the absence of the solid glutathione-agarose beads. The test compound can be added either during or after the species are allowed to interact. This mixture can then be added to the glutathione-agarose beads and unbound material is washed away. Again the extent of inhibition of the CML progression protein/binding partner interaction can be detected by adding the labeled antibody and measuring the radioactivity associated with the beads.
• In another embodiment of the invention, these same techniques can be employed using peptide fragments that correspond to the binding domains of the CML progression protein and/or the interactive binding partner (in cases where the binding partner is a protein), in place of one or both of the full length proteins. Any number of methods routinely practiced in the art can be used to identify and isolate the binding sites. These methods include, but are not limited to, mutagenesis of the gene encoding one of the proteins and screening for disruption of binding in a co-immunoprecipitation assay. Compensating mutations in the gene encoding the second species in the complex can then be selected. Sequence analysis of the genes encoding the respective proteins will reveal the mutations that correspond to the region of the protein involved in interactive binding. Alternatively, one protein can be anchored to a solid surface using methods described in this section above, and allowed to interact with and bind to its labeled binding partner, which has been treated with a proteolytic enzyme, such as trypsin. After washing, a short, labeled peptide comprising the binding domain may remain associated with the solid material, which can be isolated and identified by amino acid sequencing. Also, once the gene coding for the binding partner is obtained, short gene segments can be engineered to express peptide fragments of the protein, which can then be tested for binding activity and purified or synthesized.
• For example, and not by way of limitation, a CML progression protein can be anchored to a solid material as described in this section, above, by making a GST-CML progression protein fusion protein and allowing it to bind to glutathione agarose beads. The interactive binding partner can be labeled with a radioactive isotope, such as³⁵S, and cleaved with a proteolytic enzyme such as trypsin. Cleavage products can then be added to the anchored GST-CML progression protein fusion protein and allowed to bind. After washing away unbound peptides, labeled bound material, representing the binding partner binding domain, can be eluted, purified, and analyzed for amino acid sequence by well-known methods. Peptides so identified can be produced synthetically or fused to appropriate facilitative proteins using recombinant DNA technology.
• Some CML progression proteins are kinases. Kinase activity of a CML progression protein can be assayed in vitro using a synthetic peptide substrate of a CML progression protein of interest, e.g., a GSK-derived biotinylated peptide substrate. The phosphopeptide product is quantitated using a Homogenous Time-Resolved Fluorescence (HTRF) assay system (Park et al., 1999, Anal. Biochem.269:94-104). The reaction mixture contains suitable amounts of ATP, peptide substrate, and the CML progression protein. The peptide substrate has a suitable amino acid sequence and is biotinylated at the N-terminus. The kinase reaction is incubated, and then terminated with Stop/Detection Buffer and GSK3 cc anti-phosphoserine antibody (e.g., Cell Signaling Technologies, Beverly, Mass.; Cat#9338) labeled with europium-chelate (e.g., from Perkin Elmer, Boston, Mass.). The reaction is allowed to equilibrate, and relative fluorescent units are determined Inhibitor compounds are assayed in the reaction described above, to determine compound IC50s. A particular compound is added to in a half-log dilution series covering a suitable range of concentrations, e.g., from 1 nM to 100 μM. Relative phospho substrate formation, read as HTRF fluorescence units, is measured over the range of compound concentrations and a titration curve generated using a four parameter sigmoidal fit. Specific compounds having IC₅₀below a predetermined threshold value, e.g., ≦50 μM against a substrate, can be identified.
• The extent of peptide phosphorylation can be determined by Homogeneous Time Resolved Fluorescence (HTRF) using a lanthanide chelate (Lance)-coupled monoclonal antibody specific for the phosphopeptide in combination with a streptavidin-linked allophycocyanin (SA-APC) fluorophore which binds to the biotin moiety on the peptide. When the Lance and APC are in proximity (i.e. bound to the same phosphopeptide molecule), a non-radiative energy transfer takes place from the Lance to the APC, followed by emission of light from APC at 665 nm. The assay can be run using various assay format, e.g., streptavidin flash plate assay, streptavidin filter plate assay.
• A standard PKA assay can be used to assay the activity of protein kinase A (PKA). A standard PKC assay can be used to assay the activity of protein kinase C(PKC). The most common methods for assaying PKA or PKC activity involves measuring the transfer of³²P-labeled phosphate to a protein or peptide substrate that can be captured on phosphocellulose filters via weak electrostatic interactions.
• Kinase inhibitors can be identified using fluorescence polarization to monitor kinase activity. This assay utilizes GST-CML progression protein, peptide substrate, peptide substrate tracer, an anti-phospho monoclonal IgG, and the inhibitor compound. Reactions are incubated for a period of time and then terminated. Stopped reactions are incubated and fluorescence polarization values determined.
• In a specific embodiment, a standard SPA Filtration Assay and FlashPlate® Kinase Assay can be used to measure the activity of a CML progression protein. In these assays, GST-CML progression protein, biotinylated peptide substrate, ATP, and³³P-γ-ATP are allowed to react. After a suitable period of incubation, the reactions are terminated. In a SPA Filtration Assay, peptide substrate is allowed to bind Scintilation proximity assay (SPA) beads (Amersham Biosciences), followed by filtration on a Packard GF/B Unifilter plate and washed with phosphate buffered saline. Dried plates are sealed and the amount of³³P incorporated into the peptide substrate is determined. In a FlashPlate® Kinase Assay, a suitable amount of the reaction is transferred to streptavidin-coated FlashPlates® (NEN) and incubated. Plates are washed, dried, sealed and the amount of³³P incorporated into the peptide substrate is determined
• A standard DELFIA® Kinase Assay can also be used. In a DELFIA® Kinase Assay, GST-CML progression protein, peptide substrate, and ATP are allowed to react. After the reactions are terminated, the biotin-peptide substrates are captured in the stopped reactions. Wells are washed and reacted with anti-phospho polyclonal antibody and europium labeled anti-rabbit-IgG. Wells are washed and europium released from the bound antibody is detected.
• Other assays, such as those described in WO 04/080973, WO 02/070494, and WO 03/101444, may also be utilized to determine biological activity of the instant compounds.
5.5.2. Screening Compounds that Modulate Expression or Activity of a Gene and/or its Products
• For CML progression genes that are kinases, inhibitor compounds can be assayed for their ability to inhibit a CML progression protein in hematopoetic stem cells and/or immature myeloid cells by monitoring the phosphorylation or autophosphorylation in response to the compound. Cells are grown in culture medium. Cells are pooled, counted, seeded into 6 well dishes at 200,000 cells per well in 2 ml media, and incubated. Serial dilution series of compounds or control are added to each well and incubated. Following the incubation period, each well is washed and Protease Inhibitor Cocktail Complete is added to each well. Lysates are then transferred to microcentrifuge tubes and frozen at −80° C. Lysates are thawed on ice and cleared by centrifugation and the supernatants are transferred to clean tubes. Samples are electorphoresed and proteins are transferred onto PVDF. Blots are then blocked and probed using an antibody against phospho-serine or phospho threonine. Bound antibody is visualized using a horseradish peroxidase conjugated secondary antibody and enhanced chemiluminescence. After stripping of the first antibody set, blots are re-probed for total CML progression protein, using a monoclonal antibody specific for the CML progression protein. The CML progression protein monoclonal is detected using a sheep anti-mouse IgG coupled to horseradish peroxidase and enhanced chemiluminescence. ECL exposed films are scanned and the intensity of specific bands is quantitated. Titrations are evaluated for level of phosphor-Ser signal normalized to total CML progression protein and IC50 values are calculated.
• Detection of phosphonucleolin in cell lysates can be carried out using biotinylated anti-nucleolin antibody and ruthenylated goat anti-mouse antibody. To each well of a 96-well plate is added biotynylated anti-nucleolin antibody and streptavidin coated paramagnetic beads, along with a suitable cell lysate. The antibodies and lysate are incubated. Next, another anti-phosphonucleolin antibody are added to each well of the lysate mix and incubated. Lastly, the ruthenylated goat anti-mouse antibody in antibody buffer is added to each well and incubated. The lysate antibody mixtures are read and EC50s for compound dependent increases in phosphor-nucleolin are determined.
• The compounds identified in the screen include compounds that demonstrate the ability to selectively modulate the expression or activity of a CML progression gene or its encoded protein. These compounds include but are not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, and polypeptide molecules, aptamers, and small organic or inorganic molecules.
5.6. Methods of Performing RNA Interference
• Any method known in the art for gene silencing can be used in the present invention (see, e.g., Guo et al., 1995, Cell 81:611-620; Fire et al., 1998, Nature 391:806-811; Grant, 1999, Cell 96:303-306; Tabara et al., 1999, Cell 99:123-132; Zamore et al., 2000, Cell 101:25-33; Bass, 2000, Cell 101:235-238; Petcherski et al., 2000, Nature 405:364-368; Elbashir et al., Nature 411:494-498; Paddison et al., Proc. Natl. Acad. Sci. USA 99:1443-1448). The siRNAs targeting a gene can be designed according to methods known in the art (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, and Elbashir et al., 2002, Methods26:199-213, each of which is incorporated herein by reference in its entirety).
• An siRNA having only partial sequence homology to a target gene can also be used (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, which is incorporated herein by reference in its entirety). In one embodiment, an siRNA that comprises a sense strand contiguous nucleotide sequence of 11-18 nucleotides that is identical to a sequence of a transcript of a gene but the siRNA does not have full length homology to any sequences in the transcript is used to silence the gene. Preferably, the contiguous nucleotide sequence is in the central region of the siRNA molecules. A contiguous nucleotide sequence in the central region of an siRNA can be any continuous stretch of nucleotide sequence in the siRNA which does not begin at the 3′ end. For example, a contiguous nucleotide sequence of 11 nucleotides can be the nucleotide sequence 2-12, 3-13, 4-14, 5-15, 6-16, 7-17, 8-18, or 9-19. In preferred embodiments, the contiguous nucleotide sequence is 11-16, 11-15, 14-15, 11, 12, or 13 nucleotides in length.
• In another embodiment, an siRNA that comprises a 3′ sense strand contiguous nucleotide sequence of 9-18 nucleotides which is identical to a sequence of a transcript of a gene but which siRNA does not have full length sequence identity to any contiguous sequences in the transcript is used to silence the gene. In this application, a 3′ 9-18 nucleotide sequence is a continuous stretch of nucleotides that begins at the first paired base, i.e., it does not comprise the twobase 3′ overhang. Thus, when it is stated that a particular nucleotide sequence is at the 3′ end of the siRNA, the 2 base overhang is not considered. In preferred embodiments, the contiguous nucleotide sequence is 9-16, 9-15, 9-12, 11, 10, or 9 nucleotides in length.
• An siRNA having only partial sequence homology to its target genes is especially useful for silencing a plurality of different genes in a cell. In one embodiment, an siRNA is used to silence a plurality of different genes, the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. In preferred embodiments, the central contiguous nucleotide sequence is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence is 9-15, 9-12, 11, 10, or 9 nucleotides in length.
• In one embodiment, in vitro siRNA transfection is carried out as follows: one day prior to transfection, 100 microliters of chosen cells, e.g., cervical cancer HeLa cells (ATCC, Cat. No. CCL-2), grown in DMEM/10% fetal bovine serum (Invitrogen, Carlsbad, Calif.) to approximately 90% confluency are seeded in a 96-well tissue culture plate (Corning, Corning, N.Y.) at 1500 cells/well. For each transfection 85 microliters of OptiMEM (Invitrogen) is mixed with 5 microliter of serially diluted siRNA (Dharma on, Denver) from a 20 micro molar stock. For eachtransfection 5 microliter OptiMEM is mixed with 5 microliter Oligofectamine reagent (Invitrogen) and incubated 5 minutes at room temperature. The 10 microliter OptiMEM/Oligofectamine mixture is dispensed into each tube with the OptiMEM/siRNA mixture, mixed and incubated 15-20 minutes at room temperature. 10 microliter of the transfection mixture is aliquoted into each well of the 96-well plate and incubated for 4 hours at 37° C. and 5% CO₂.
• In preferred embodiments, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting the secondary target gene at different sequence regions is used to transfect the cells. In another preferred embodiment, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting two or more different target genes is used to transfect the cells.
• In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually, e.g., 100 nM. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has an concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene.
• Another method for gene silencing is to introduce an shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev.16, 948-958; Brummelkamp et al., 2002, Science296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA99, 5515-5520, all of which are incorporated by reference herein in their entirety), which can be processed in the cells into siRNA. In this method, a desired siRNA sequence is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo, e.g., in animals (see, McCaffrey et al. 2002, Nature418, 38-39; Xia et al., 2002, Nat. Biotech.20, 1006-1010; Lewis et al., 2002, Nat. Genetics32, 107-108; Rubinson et al., 2003, Nat.Genetics33, 401-406; Tiscornia et al., 2003, Proc. Natl.Acad. Sci. USA100, 1844-1848, all of which are incorporated by reference herein in their entirety). Thus, in one embodiment, a plasmid-based shRNA is used.
• In a preferred embodiment, shRNAs are expressed from recombinant vectors introduced either transiently or stably integrated into the genome (see, e.g., Paddison et al., 2002, Genes Dev16:948-958; Sui et al., 2002, Proc Natl Acad Sci USA99:5515-5520; Yu et al., 2002, Proc Natl Acad Sci USA99:6047-6052; Miyagishi et al., 2002, Nat Biotechnol20:497-500; Paul et al., 2002, Nat Biotechnol20:505-508; Kwak et al., 2003, J Pharmacol Sci93:214-217; Brummelkamp et al., 2002, Science296:550-553; Boden et al., 2003, Nucleic Acids Res31:5033-5038; Kawasaki et al., 2003, Nucleic Acids Res31:700-707). The siRNA that disrupts the target gene can be expressed (via an shRNA) by any suitable vector which encodes the shRNA. The vector can also encode a marker which can be used for selecting clones in which the vector or a sufficient portion thereof is integrated in the host genome such that the shRNA is expressed. Any standard method known in the art can be used to deliver the vector into the cells. In one embodiment, cells expressing the shRNA are generated by transfecting suitable cells with a plasmid containing the vector. Cells can then be selected by the appropriate marker. Clones are then picked, and tested for knockdown. In a preferred embodiment, the expression of the shRNA is under the control of an inducible promoter such that the silencing of its target gene can be turned on when desired. Inducible expression of an siRNA is particularly useful for targeting essential genes.
• In one embodiment, the expression of the shRNA is under the control of a regulated promoter that allows tuning of the silencing level of the target gene. This allows screening against cells in which the target gene is partially knocked out. As used herein, a “regulated promoter” refers to a promoter that can be activated when an appropriate inducing agent is present. An “inducing agent” can be any molecule that can be used to activate transcription by activating the regulated promoter. An inducing agent can be, but is not limited to, a peptide or polypeptide, a hormone, or an organic small molecule. An analogue of an inducing agent, i.e., a molecule that activates the regulated promoter as the inducing agent does, can also be used. The level of activity of the regulated promoter induced by different analogues may be different, thus allowing more flexibility in tuning the activity level of the regulated promoter. The regulated promoter in the vector can be any mammalian transcription regulation system known in the art (see, e.g., Gossen et al, 1995, Science 268:1766-1769; Lucas et al, 1992, Annu. Rev. Biochem. 61:1131; Li et al., 1996, Cell 85:319-329; Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517; and Pollock et al., 2000, Proc. Natl. Acad. Sci. USA 97:13221-13226). In preferred embodiments, the regulated promoter is regulated in a dosage and/or analogue dependent manner. In one embodiment, the level of activity of the regulated promoter is tuned to a desired level by a method comprising adjusting the concentration of the inducing agent to which the regulated promoter is responsive. The desired level of activity of the regulated promoter, as obtained by applying a particular concentration of the inducing agent, can be determined based on the desired silencing level of the target gene.
• In one embodiment, a tetracycline regulated gene expression system is used (see, e.g., Gossen et al, 1995, Science 268:1766-1769; U.S. Pat. No. 6,004,941). A tet regulated system utilizes components of the tet repressor/operator/inducer system of prokaryotes to regulate gene expression in eukaryotic cells. Thus, the invention provides methods for using the tet regulatory system for regulating the expression of an shRNA linked to one or more tet operator sequences. The methods involve introducing into a cell a vector encoding a fusion protein that activates transcription. The fusion protein comprises a first polypeptide that binds to a tet operator sequence in the presence of tetracycline or a tetracycline analogue operatively linked to a second polypeptide that activates transcription in cells. By modulating the concentration of a tetracycline, or a tetracycline analogue, expression of the tet operator-linked shRNA is regulated.
• In other embodiments, an ecdyson regulated gene expression system (see, e.g., Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517), or an MMTV glucocorticoid response element regulated gene expression system (see, e.g., Lucas et al, 1992, Annu. Rev. Biochem. 61:1131) may be used to regulate the expression of the shRNA.
• In one embodiment, the pRETRO-SUPER (pRS) vector which encodes a puromycin-resistance marker and drives shRNA expression from an H1 (RNA Pol III) promoter is used. The pRS-shRNA plasmid can be generated by any standard method known in the art. In one embodiment, the pRS-shRNA is deconvoluted from the library plasmid pool for a chosen gene by transforming bacteria with the pool and looking for clones containing only the plasmid of interest. Preferably, a 19mer siRNA sequence is used along with suitable forward and reverse primers for sequence specific PCR. Plasmids are identified by sequence specific PCR, and confirmed by sequencing. Cells expressing the shRNA are generated by transfecting suitable cells with the pRS-shRNA plasmid. Cells are selected by the appropriate marker, e.g., puromycin, and maintained until colonies are evident. Clones are then picked, and tested for knockdown. In another embodiment, an shRNA is expressed by a plasmid, e.g., a pRS-shRNA. The knockdown by the pRS-shRNA plasmid, can be achieved by transfecting cells using Lipofectamine 2000 (Invitrogen).
• In yet another method, siRNAs can be delivered to an organ or tissue in an animal, such a human, in vivo (see, e.g., Song et al. 2003, Nat.Medicine9, 347-351; Sorensen et al., 2003, J. Mol. Biol.327, 761-766; Lewis et al., 2002, Nat. Genetics32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the animal. The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the animal.
5.7. Production of CML Progression/Target or IM Resistance Proteins and Peptides
• CML progression proteins, or peptide fragments thereof, can be prepared for uses according to the present invention. For example, CML progression proteins, or peptide fragments thereof, can be used for the generation of antibodies, in diagnostic assays, for screening of inhibitors, or for the identification of other cellular gene products involved in the regulation of expression and/or activity of a CML progression gene.
• The CML progression proteins or peptide fragments thereof, may be produced by recombinant DNA technology using techniques well known in the art. The amino acid sequences of the CML progression proteins are well-known and can be obtained from, e.g., GenBank®. Methods which are well known to those skilled in the art can be used to construct expression vectors containing CML progression protein coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.
• A variety of host-expression vector systems may be utilized to express the CML progression gene coding sequences. Such host-expression systems represent vehicles by which the coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide coding sequences, exhibit the CML progression protein in situ. These include but are not limited to microorganisms such as bacteria (e.g.,E. coli, B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing CML progression protein coding sequences; yeast (e.g.,Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing the CML progression protein coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing the CML progression protein coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing CML progression protein coding sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3, N2a) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).
• In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the CML progression protein being expressed. For example, when a large quantity of such a protein is to be produced, for the generation of pharmaceutical compositions of CML progression protein protein or for raising antibodies to CML progression protein protein, for example, vectors which direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to theE. coliexpression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which the CML progression protein coding sequence may be ligated individually into the vector in frame with the lac Z coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem. 264:5503-5509); and the like. pGEX vectors may also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione. The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety.
• In an insect system,Autographa californicanuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes. The virus grows inSpodoptera frugiperdacells. The CML progression gene coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of CML progression gene coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infectSpodoptera frugiperdacells in which the inserted gene is expressed. (E.g., see Smith et al., 1983, J. Virol. 46: 584; Smith, U.S. Pat. No. 4,215,051).
• In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the CML progression gene coding sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing CML progression protein in infected hosts. (E.g., See Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted CML progression protein coding sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire CML progression gene, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of the CML progression gene coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see Bittner et al., 1987, Methods in Enzymol. 153:516-544).
• In addition, a host cell strain may be chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include but are not limited to CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, WI38.
• For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the CML progression protein may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express the CML progression protein. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of the CML progression protein.
• In another embodiment, the expression characteristics of an endogenous gene (e.g., a CML progression gene) within a cell, cell line or microorganism may be modified by inserting a DNA regulatory element heterologous to the endogenous gene of interest into the genome of a cell, stable cell line or cloned microorganism such that the inserted regulatory element is operatively linked with the endogenous gene (e.g., a CML progression gene) and controls, modulates, activates, or inhibits the endogenous gene. For example, endogenous CML progression genes which are normally “transcriptionally silent”, i.e., a CML progression gene which is normally not expressed, or is expressed only at very low levels in a cell line or microorganism, may be activated by inserting a regulatory element which is capable of promoting the expression of the gene product in that cell line or microorganism. Alternatively, transcriptionally silent, endogenous CML progression genes may be activated by insertion of a promiscuous regulatory element that works across cell types.
• A heterologous regulatory element may be inserted into a stable cell line or cloned microorganism, such that it is operatively linked with and activates or inhibits expression of endogenous CML progression genes, using techniques, such as targeted homologous recombination, which are well known to those of skill in the art, and described e.g., in Chappel, U.S. Pat. No. 5,272,071; PCT Publication No. WO 91/06667 published May 16, 1991; Skoultchi, U.S. Pat. No. 5,981,214; and Treco et al U.S. Pat. No. 5,968,502 and PCT Publication No. WO 94/12650 published Jun. 9, 1994. Alternatively, non-targeted, e.g. non-homologous recombination techniques may be used which are well-known to those of skill in the art and described, e.g., in PCT Publication No. WO 99/15650 published Apr. 1, 1999.
• CML progression gene activation (or inactivation) may also be accomplished using designer transcription factors using techniques well known in the art. Briefly, a designer zinc finger protein transcription factor (ZFP-TF) is made which is specific for a regulatory region of the CML progression gene to be activated or inactivated. A construct encoding this designer ZFP-TF is then provided to a host cell in which the CML progression gene is to be controlled. The construct directs the expression of the designer ZFP-TF protein, which in turn specifically modulates the expression of the endogenous CML progression gene. The following references relate to various aspects of this approach in further detail: Wang & Pabo, 1999, Proc. Natl. Acad. Sci. USA 96, 9568; Berg, 1997, Nature Biotechnol. 15, 323; Greisman & Pabo, 1997, Science 275, 657; Berg & Shi, 1996, Science 271, 1081; Rebar & Pabo, 1994, Science 263, 671; Rhodes & Klug, 1993, Scientific American 269, 56; Pavletich & Pabo, 1991, Science 252, 809; Liu et al., 2001, J. Biol. Chem. 276, 11323; Zhang et al., 2000, J. Biol. Chem. 275, 33850; Beerli et al., 2000, Proc. Natl. Acad. Sci. USA 97, 1495; Kang et al., 2000, J. Biol. Chem. 275, 8742; Beerli et al., 1998, Proc. Natl. Acad. Sci. USA 95, 14628; Kim & Pabo, 1998, Proc. Natl. Acad. Sci. USA 95, 2812; Choo et al., 1997, J. Mol. Biol. 273, 525; Kim & Pabo, 1997, J. Biol. Chem. 272, 29795; Liu et al, 1997, Proc. Natl. Acad. Sci. USA 94, 5525; Kim et al, 1997, Proc. Natl. Acad. Sci. USA 94, 3616; Kikyo et al., 2000, Science 289, 2360; Robertson & Wolffe, 2000, Nature Reviews 1, 11; and Gregory, 2001, Curr. Opin. Genet. Devt. 11, 142.
• A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al., 1980, Cell 22:817) genes can be employed in tk⁻, hgprt⁻ or aprt⁻ cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler, et al., 1980, Natl. Acad. Sci. USA 77:3567; O'Hare, et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al., 1984, Gene 30:147).
• Alternatively, any fusion protein may be readily purified by utilizing an antibody specific for the fusion protein being expressed. For example, a system described by Janknecht et al. allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht, et al., 1991, Proc. Natl. Acad. Sci. USA 88: 8972-8976). In this system, the gene of interest is subcloned into a vaccinia recombination plasmid such that the gene's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni²⁺.nitriloacetic acid-agarose columns and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.
• In a specific embodiment, recombinant human CML progression proteins can be expressed as a fusion protein with glutathione S-transferase at the amino-terminus (GST-CML progression protein) using standard baculovirus vectors and a (Bac-to-Bac®) insect cell expression system purchased from GIBCO™ Invitrogen. Recombinant protein expressed in insect cells can be purified using glutathione sepharose (Amersham Biotech) using standard procedures described by the manufacturer.
5.8. Production of Antibodies that Bind a CML Progression/Target or IM Resistance Protein
• CML progression protein or a fragment thereof can be used to raise antibodies which bind CML progression protein. Such antibodies include but are not limited to polyclonal, monoclonal, chimeric, single chain, Fab fragments, and an Fab expression library. In a preferred embodiment, anti CML progression protein C-terminal antibodies are raised using an appropriate C-terminal fragment of a CML progression protein, e.g., the kinase domain. Such antibodies bind the kinase domain of the CML progression protein. In another preferred embodiment, anti CML progression protein N-terminal antibodies are raised using an appropriate N-terminal fragment of a CML progression protein. The N-terminal domain of a CML progression protein are less homologous to other kinases, and therefore offered a more specific target for a particular CML progression protein.
5.8.1. Production of Monoclonal Antibodies Specific for a CML Progression/Target or Im Resistance Protein
• Antibodies can be prepared by immunizing a suitable subject with a CML progression protein or a fragment thereof as an immunogen. The antibody titer in the immunized subject can be monitored over time by standard techniques, such as with an enzyme linked immunosorbent assay (ELISA) using immobilized polypeptide. If desired, the antibody molecules can be isolated from the mammal (e.g., from the blood) and further purified by well-known techniques, such as protein A chromatography to obtain the IgG fraction.
• At an appropriate time after immunization, e.g., when the specific antibody titers are highest, antibody-producing cells can be obtained from the subject and used to prepare monoclonal antibodies by standard techniques, such as the hybridoma technique originally described by Kohler and Milstein (1975, Nature 256:495-497), the human B cell hybridoma technique by Kozbor et al. (1983, Immunol. Today 4:72), the EBV-hybridoma technique by Cole et al. (1985, Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96) or trioma techniques. The technology for producing hybridomas is well known (see Current Protocols in Immunology, 1994, John Wiley & Sons, Inc., New York, N.Y.). Hybridoma cells producing a monoclonal antibody are detected by screening the hybridoma culture supernatants for antibodies that bind the polypeptide of interest, e.g., using a standard ELISA assay.
• Monoclonal antibodies are obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Thus, the modifier “monoclonal” indicates the character of the antibody as not being a mixture of discrete antibodies. For example, the monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., 1975, Nature, 256:495, or may be made by recombinant DNA methods (U.S. Pat. No. 4,816,567). The term “monoclonal antibody” as used herein also indicates that the antibody is an immunoglobulin.
• In the hybridoma method of generating monoclonal antibodies, a mouse or other appropriate host animal, such as a hamster, is immunized as hereinabove described to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization (see, e.g., U.S. Pat. No. 5,914,112, which is incorporated herein by reference in its entirety).
• Alternatively, lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986)). The hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.
• Preferred myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. Among these, preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, Calif. USA, and SP-2 cells available from the American Type Culture Collection, Rockville, Md. USA.
• Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, 1984, J. Immunol., 133:3001; Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987)). Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immuno-absorbent assay (ELISA). The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson et al., 1980, Anal. Biochem., 107:220.
• After hybridoma cells are identified that produce antibodies of the desired specificity, affinity, and/or activity, the clones may be subcloned by limiting dilution procedures and grown by standard methods (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103, Academic Press, 1986). Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal. The monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, ascites fluid, or serum by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
• Alternative to preparing monoclonal antibody-secreting hybridomas, a monoclonal antibody directed against a CML progression protein or a fragment thereof can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with the CML progression protein or the fragment. Kits for generating and screening phage display libraries are commercially available (e.g., Pharmacia Recombinant Phage Antibody System, Catalog No. 27-9400-01; and the Stratagene antigen SurfZAP™ Phage Display Kit, Catalog No. 240612). Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734.
• In addition, techniques developed for the production of “chimeric antibodies” (Morrison, et al., 1984, Proc. Natl. Acad. Sci., 81, 6851-6855; Neuberger, et al., 1984, Nature 312, 604-608; Takeda, et al., 1985, Nature, 314, 452-454) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region. (See, e.g., Cabilly et al., U.S. Pat. No. 4,816,567; and Boss et al., U.S. Pat. No. 4,816,397, which are incorporated herein by reference in their entirety.)
• Humanized antibodies are antibody molecules from non-human species having one or more complementarity determining regions (CDRs) from the non-human species and a framework region from a human immunoglobulin molecule. (see e.g., U.S. Pat. No. 5,585,089, which is incorporated herein by reference in its entirety.) Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using methods described in PCT Publication No. WO 87/02671; European Patent Application 184,187; European Patent Application 171,496; European Patent Application 173,494; PCT Publication No. WO 86/01533; U.S. Pat. Nos. 4,816,567 and 5,225,539; European Patent Application 125,023; Better et al., 1988, Science 240:1041-1043; Liu et al., 1987, Proc. Natl. Acad. Sci. USA 84:3439-3443; Liu et al., 1987, J. Immunol. 139:3521-3526; Sun et al., 1987, Proc. Natl. Acad. Sci. USA 84:214-218; Nishimura et al., 1987, Canc. Res. 47:999-1005; Wood et al., 1985, Nature 314:446-449; Shaw et al., 1988, J. Natl. Cancer Inst. 80:1553-1559; Morrison 1985, Science 229:1202-1207; Oi et al., 1986, Bio/Techniques 4:214; Jones et al., 1986, Nature 321:552-525; Verhoeyan et al., 1988, Science 239:1534; and Beidler et al., 1988, J. Immunol. 141:4053-4060.
• Complementarity determining region (CDR) grafting is another method of humanizing antibodies. It involves reshaping murine antibodies in order to transfer full antigen specificity and binding affinity to a human framework (Winter et al. U.S. Pat. No. 5,225,539). CDR-grafted antibodies have been successfully constructed against various antigens, for example, antibodies against IL-2 receptor as described in Queen et al., 1989 (Proc. Natl. Acad. Sci. USA 86:10029); antibodies against cell surface receptors-CAMPATH as described in Riechmann et al. (1988, Nature, 332:323; antibodies against hepatitis B in Cole et al. (1991, Proc. Natl. Acad. Sci. USA 88:2869); as well as against viral antigens-respiratory syncitial virus in Tempest et al. (1991, Bio-Technology 9:267). CDR-grafted antibodies are generated in which the CDRs of the murine monoclonal antibody are grafted into a human antibody. Following grafting, most antibodies benefit from additional amino acid changes in the framework region to maintain affinity, presumably because framework residues are necessary to maintain CDR conformation, and some framework residues have been demonstrated to be part of the antigen binding site. However, in order to preserve the framework region so as not to introduce any antigenic site, the sequence is compared with established germline sequences followed by computer modeling.
• Completely human antibodies are particularly desirable for therapeutic treatment of human patients. Such antibodies can be produced using transgenic mice which are incapable of expressing endogenous immunoglobulin heavy and light chain genes, but which can express human heavy and light chain genes. The transgenic mice are immunized in the normal fashion with a CML progression protein.
• Monoclonal antibodies directed against a CML progression protein can be obtained using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation. Thus, using such a technique, it is possible to produce therapeutically useful IgG, IgA and IgE antibodies. For an overview of this technology for producing human antibodies, see Lonberg and Huszar (1995, Int. Rev. Immunol. 13:65-93). For a detailed discussion of this technology for producing human antibodies and human monoclonal antibodies and protocols for producing such antibodies, see e.g., U.S. Pat. No. 5,625,126; U.S. Pat. No. 5,633,425; U.S. Pat. No. 5,569,825; U.S. Pat. No. 5,661,016; and U.S. Pat. No. 5,545,806. In addition, companies such as Abgenix, Inc. (Freemont, Calif., see, for example, U.S. Pat. No. 5,985,615) and Medarex, Inc. (Princeton, N.J.), can be engaged to provide human antibodies directed against a CML progression protein or a fragment thereof using technology similar to that described above.
• Completely human antibodies which recognize and bind a selected epitope can be generated using a technique referred to as “guided selection.” In this approach a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope (Jespers et al., 1994, Bio/technology 12:899-903).
• A pre-existing anti-CML progression protein antibody can be used to isolate additional antigens of the CML progression protein by standard techniques, such as affinity chromatography or immunoprecipitation for use as immunogens. Moreover, such an antibody can be used to detect the protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of CML progression protein. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.
5.8.2. Production of Polyclonal Anti-CML Progression/Target or IM Resistance Protein Antibodies
• The anti-CML progression protein antibodies can be produced by immunization of a suitable animal, such as but are not limited to mouse, rabbit, and horse.
• An immunogenic preparation comprising a CML progression protein or a fragment thereof can be used to prepare antibodies by immunizing a suitable subject (e.g., rabbit, goat, mouse or other mammal). An appropriate immunogenic preparation can contain, for example, recombinantly expressed or chemically synthesized CML progression protein peptide or polypeptide. The preparation can further include an adjuvant, such as Freund's complete or incomplete adjuvant, or similar immunostimulatory agent.
• A fragment of a CML progression protein suitable for use as an immunogen comprises at least a portion of the CML progression protein that is 8 amino acids, more preferably 10 amino acids and more preferably still, 15 amino acids long.
• The invention also provides chimeric or fusion CML progression protein polypeptides for use as immunogens. As used herein, a “chimeric” or “fusion” CML progression protein polypeptide comprises all or part of a CML progression protein polypeptide operably linked to a heterologous polypeptide. Within the fusion CML progression protein polypeptide, the term “operably linked” is intended to indicate that the CML progression protein polypeptide and the heterologous polypeptide are fused in-frame to each other. The heterologous polypeptide can be fused to the N-terminus or C-terminus of the CML progression protein polypeptide.
• One useful fusion CML progression protein polypeptide is a GST fusion CML progression protein polypeptide in which the CML progression protein polypeptide is fused to the C-terminus of GST sequences. Such fusion CML progression protein polypeptides can facilitate the purification of a recombinant CML progression protein polypeptide.
• In another embodiment, the fusion CML progression protein polypeptide contains a heterologous signal sequence at its N-terminus so that the CML progression protein polypeptide can be secreted and purified to high homogeneity in order to produce high affinity antibodies. For example, the native signal sequence of an immunogen can be removed and replaced with a signal sequence from another protein. For example, the gp67 secretory sequence of the baculovirus envelope protein can be used as a heterologous signal sequence (Current Protocols in Molecular Biology, Ausubel et al., eds., John Wiley & Sons, 1992). Other examples of eukaryotic heterologous signal sequences include the secretory sequences of melittin and human placental alkaline phosphatase (Stratagene; La Jolla, Calif.). In yet another example, useful prokaryotic heterologous signal sequences include the phoA secretory signal and the protein A secretory signal (Pharmacia Biotech; Piscataway, N.J.).
• In yet another embodiment, the fusion CML progression protein polypeptide is an immunoglobulin fusion protein in which all or part of a CML progression protein polypetide is fused to sequences derived from a member of the immunoglobulin protein family. The immunoglobulin fusion proteins can be used as immunogens to produce antibodies directed against the CML progression protein polypetide in a subject.
• Chimeric and fusion CML progression protein polypeptide can be produced by standard recombinant DNA techniques. In one embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (e.g., Ausubel et al., supra). Moreover, many expression vectors are commercially available that already encode a fusion domain (e.g., a GST polypeptide). A nucleic acid encoding an immunogen can be cloned into such an expression vector such that the fusion domain is linked in-frame to the polypeptide.
• The CML progression protein immunogenic preparation is then used to immunize a suitable animal. Preferably, the animal is a specialized transgenic animal that can secret human antibody. Non-limiting examples include transgenic mouse strains which can be used to produce a polyclonal population of antibodies directed to a specific pathogen (Fishwild et al., 1996, Nature Biotechnology 14:845-851; Mendez et al., 1997, Nature Genetics 15:146-156). In one embodiment of the invention, transgenic mice that harbor the unrearranged human immunoglobulin genes are immunized with the target immunogens. After a vigorous immune response against the immunogenic preparation has been elicited in the mice, the blood of the mice are collected and a purified preparation of human IgG molecules can be produced from the plasma or serum. Any method known in the art can be used to obtain the purified preparation of human IgG molecules, including but is not limited to affinity column chromatography using anti-human IgG antibodies bound to a suitable column matrix. Anti-human IgG antibodies can be obtained from any sources known in the art, e.g., from commercial sources such as Dako Corporation and ICN. The preparation of IgG molecules produced comprises a polyclonal population of IgG molecules that bind to the immunogen or immunogens at different degree of affinity. Preferably, a substantial fraction of the preparation contains IgG molecules specific to the immunogen or immunogens. Although polyclonal preparations of IgG molecules are described, it is understood that polyclonal preparations comprising any one type or any combination of different types of immunoglobulin molecules are also envisioned and are intended to be within the scope of the present invention.
• A population of antibodies directed to a CML progression protein can be produced from a phage display library. Polyclonal antibodies can be obtained by affinity screening of a phage display library having a sufficiently large and diverse population of specificities with a CML progression protein or a fragment thereof. Examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734. A phage display library permits selection of desired antibody or antibodies from a very large population of specificities. An additional advantage of a phage display library is that the nucleic acids encoding the selected antibodies can be obtained conveniently, thereby facilitating subsequent construction of expression vectors.
• In other preferred embodiments, the population of antibodies directed to a CML progression protein or a fragment thereof is produced by a method using the whole collection of selected displayed antibodies without clonal isolation of individual members as described in U.S. Pat. No. 6,057,098, which is incorporated by reference herein in its entirety. Polyclonal antibodies are obtained by affinity screening of a phage display library having a sufficiently large repertoire of specificities with, e.g., an antigenic molecule having multiple epitopes, preferably after enrichment of displayed library members that display multiple antibodies. The nucleic acids encoding the selected display antibodies are excised and amplified using suitable PCR primers. The nucleic acids can be purified by gel electrophoresis such that the full length nucleic acids are isolated. Each of the nucleic acids is then inserted into a suitable expression vector such that a population of expression vectors having different inserts is obtained. The population of expression vectors is then expressed in a suitable host.
5.8.3 Production of Antibody-Drug Conjugates Targeting a CML Progression/Target or IM Resistance Protein
• Cancer cells can be targeted and killed using anti-CML progression protein antibody-drug conjugates that target an advanced phase CML hematopoetic stem cell and/or immature myeloid cell expressing a CML progression protein on its surface, e.g., PRAME. For example, an antibody specific for a CML progression protein may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion. Antibody-drug conjugates can be prepared by method known in the art (see, e.g., Immunoconjugates, Vogel, ed. 1987; Targeted Drugs, Goldberg, ed. 1983; Antibody Mediated Delivery Systems, Rodwell, ed. 1988). Therapeutic drugs, such as but are not limited to, paclitaxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof, can be conjugated to anti-CML progression protein antibodies. Other therapeutic agents that can be conjugated to anti-CML progression protein antibodies include, but are not limited to, antimetabolites, e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine; alkylating agents, e.g., mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin; anthracyclines, e.g., daunorubicin (daunomycin) and doxorubicin; antibiotics, e.g., dactinomycin (actinomycin), bleomycin, mithramycin, anthramycin (AMC); and anti-mitotic agents, e.g., vincristine and vinblastine. The therapeutic agents that can be conjugated to anti-CML progression protein antibodies may also be a protein or polypeptide possessing a desired biological activity. Other chemotherapeutic agents known in the art, such as those described in Section 5.8.5, infra, can also be conjugated with such an anti-CML progression protein antibody. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin.
• The drug molecules can be linked to the anti-CML progression protein antibody via a linker. Any suitable linker can be used for the preparation of such conjugates. In some embodiments, the linker can be a linker that allows the drug molecules to be released from the conjugates in unmodified form at the target site.
• The antibodies can also be used diagnostically to, for example, monitor the presence of cancer cells as part of a clinical testing procedure to, e.g., determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron emitting metals using various positron emission tomographies, and nonradioactive paramagnetic metal ions. See generally U.S. Pat. No. 4,741,900 for metal ions which can be conjugated to antibodies for use as diagnostics according to the present invention. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include fluorescent proteins, e.g., green fluorescent protein (GFP), umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include¹²⁵I,¹³¹I,¹¹¹In,¹⁷⁷Lu,⁹⁰Y or⁹⁹Tc.
• Techniques for conjugating therapeutic moieties to antibodies are well known, see, e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy”, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery”, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review”, in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy”, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., “The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates”, Immunol. Rev., 62:119-58 (1982); each of which is incorporated herein by reference.
• Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Pat. No. 4,676,980, which is incorporated herein by reference.
5.8.4 Production of Peptides
• A CML progression protein-binding peptide or polypeptide or peptide or polypeptide of a CML progression protein may be produced by recombinant DNA technology using techniques well known in the art. Thus, the polypeptide or peptide can be produced by expressing nucleic acid containing sequences encoding the polypeptide or peptide. Methods which are well known to those skilled in the art can be used to construct expression vectors containing coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein polypeptide sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.
5.8.5 Chemotherapeutic Drugs
• The invention can be practiced with any known chemotherapeutic drugs, including but not limited to DNA damaging agents, anti-metabolites, anti-mitotic agents, or a combination of two or more of such known anti-cancer agents.
• DNA damage agents cause chemical damage to DNA and/or RNA. DNA damage agents can disrupt DNA replication or cause the generation of nonsense DNA or RNA. DNA damaging agents include but are not limited to topoisomerase inhibitor, DNA binding agent, and ionizing radiation. A topoisomerase inhibitor that can be used in conjunction with the invention can be a topoisomerase I (Topo I) inhibitor, a topoisomerase II (Topo II) inhibitor, or a dual topoisomerase I and II inhibitor. A topo I inhibitor can be for example from any of the following classes of compounds: camptothecin analogue (e.g., karenitecin, aminocamptothecin, lurtotecan, topotecan, irinotecan, BAY 56-3722, rubitecan, GI14721, exatecan mesylate), rebeccamycin analogue, PNU 166148, rebeccamycin, TAS-103, camptothecin (e.g., camptothecin polyglutamate, camptothecin sodium), intoplicine, ecteinascidin 743, J-107088, pibenzimol Examples of preferred topo I inhibitors include but are not limited to camptothecin, topotecan (hycaptamine), irinotecan (irinotecan hydrochloride), belotecan, or an analogue or derivative of any of the foregoing.
• A topo II inhibitor that can be used in conjunction with the invention can be for example from any of the following classes of compounds: anthracycline antibiotics (e.g., carubicin, pirarubicin, daunorubicin citrate liposomal, daunomycin, 4-iodo-4-doxydoxorubicin, doxorubicin, n,n-dibenzyl daunomycin, morpholinodoxorubicin, aclacinomycin antibiotics, duborimycin, menogaril, nogalamycin, zorubicin, epirubicin, marcellomycin, detorubicin, annamycin, 7-cyanoquinocarcinol, deoxydoxorubicin, idarubicin, GPX-100, MEN-10755, valrubicin, KRN5500), epipodophyllotoxin compound (e.g., podophyllin, teniposide, etoposide, GL331, 2-ethylhydrazide), anthraquinone compound (e.g., ametantrone, bisantrene, mitoxantrone, anthraquinone), ciprofloxacin, acridine carboxamide, amonafide, anthrapyrazole antibiotics (e.g., teloxantrone, sedoxantrone trihydrochloride, piroxantrone, anthrapyrazole, losoxantrone), TAS-103, fostriecin, razoxane, XK469R, XK469, chloroquinoxaline sulfonamide, merbarone, intoplicine, elsamitrucin, CI-921, pyrazoloacridine, elliptinium, amsacrine. Examples of preferred topo II inhibitors include but are not limited to doxorubicin (Adriamycin), etoposide phosphate (etopofos), teniposide, sobuzoxane, or an analogue or derivative of any of the foregoing.
• DNA binding agents that can be used in conjunction with the invention include but are not limited to a DNA groove binding agent, e.g., DNA minor groove binding agent; DNA crosslinking agent; intercalating agent; and DNA adduct forming agent. A DNA minor groove binding agent can be an anthracycline antibiotic, mitomycin antibiotic (e.g., porfiromycin, KW-2149, mitomycin B, mitomycin A, mitomycin C), chromomycin A3, carzelesin, actinomycin antibiotic (e.g., cactinomycin, dactinomycin, actinomycin F1), brostallicin, echinomycin, bizelesin, duocarmycin antibiotic (e.g., KW 2189), adozelesin, olivomycin antibiotic, plicamycin, zinostatin, distamycin, MS-247, ecteinascidin 743, amsacrine, anthramycin, and pibenzimol, or an analogue or derivative of any of the foregoing.
• DNA crosslinking agents include but are not limited to antineoplastic alkylating agent, methoxsalen, mitomycin antibiotic, psoralen. An antineoplastic alkylating agent can be a nitrosourea compound (e.g., cystemustine, tauromustine, semustine, PCNU, streptozocin, SarCNU, CGP-6809, carmustine, fotemustine, methylnitrosourea, nimustine, ranimustine, ethylnitrosourea, lomustine, chlorozotocin), mustard agent (e.g., nitrogen mustard compound, such as spiromustine, trofosfamide, chlorambucil, estramustine, 2,2,2-trichlorotriethylamine, prednimustine, novembichin, phenamet, glufosfamide, peptichemio, ifosfamide, defosfamide, nitrogen mustard, phenesterin, mannomustine, cyclophosphamide, melphalan, perfosfamide, mechlorethamine oxide hydrochloride, uracil mustard, bestrabucil, DHEA mustard, tallimustine, mafosfamide, aniline mustard, chlornaphazine; sulfur mustard compound, such as bischloroethylsulfide; mustard prodrug, such as TLK286 and ZD2767), ethylenimine compound (e.g., mitomycin antibiotic, ethylenimine, uredepa, thiotepa, diaziquone, hexamethylene bisacetamide, pentamethylmelamine, altretamine, carzinophilin, triaziquone, meturedepa, benzodepa, carboquone), alkylsulfonate compound (e.g., dimethylbusulfan, Yoshi-864, improsulfan, piposulfan, treosulfan, busulfan, hepsulfam), epoxide compound (e.g., anaxirone, mitolactol, dianhydrogalactitol, teroxirone), miscellaneous alkylating agent (e.g., ipomeanol, carzelesin, methylene dimethane sulfonate, mitobronitol, bizelesin, adozelesin, piperazinedione, VNP40101M, asaley, 6-hydroxymethylacylfulvene, EO9, etoglucid, ecteinascidin 743, pipobroman), platinum compound (e.g., ZD0473, liposomal-cisplatin analogue, satraplatin, BBR 3464, spiroplatin, ormaplatin, cisplatin, oxaliplatin, carboplatin, lobaplatin, zeniplatin, iproplatin), triazene compound (e.g., imidazole mustard, CB10-277, mitozolomide, temozolomide, procarbazine, dacarbazine), picoline compound (e.g., penclomedine), or an analogue or derivative of any of the foregoing. Examples of preferred alkylating agents include but are not limited to cisplatin, dibromodulcitol, fotemustine, ifosfamide (ifosfamid), ranimustine (ranomustine), nedaplatin (latoplatin), bendamustine (bendamustine hydrochloride), eptaplatin, temozolomide (methazolastone), carboplatin, altretamine (hexamethylmelamine), prednimustine, oxaliplatin (oxalaplatinum), carmustine, thiotepa, leusulfon (busulfan), lobaplatin, cyclophosphamide, bisulfan, melphalan, and chlorambucil, or an analogue or derivative of any of the foregoing.
• Intercalating agents can be an anthraquinone compound, bleomycin antibiotic, rebeccamycin analogue, acridine, acridine carboxamide, amonafide, rebeccamycin, anthrapyrazole antibiotic, echinomycin, psoralen, LU 79553, BW A773U, crisnatol mesylate, benzo(a)pyrene-7,8-diol-9,10-epoxide, acodazole, elliptinium, pixantrone, or an analogue or derivative of any of the foregoing.
• DNA adduct forming agents include but are not limited to enediyne antitumor antibiotic (e.g., dynemicin A, esperamicin A1, zinostatin, dynemicin, calicheamicin gamma 11), platinum compound, carmustine, tamoxifen (e.g., 4-hydroxy-tamoxifen), psoralen, pyrazine diazohydroxide, benzo(a)pyrene-7,8-diol-9,10-epoxide, or an analogue or derivative of any of the foregoing.
• Anti-metabolites block the synthesis of nucleotides or deoxyribonucleotides, which are necessary for making DN, thereby preventing cells from replicating. Anti-metabolites include but are not limited to cytosine, arabinoside, floxuridine, 5-fluorouracil (5-FU), mercaptopurine, gemcitabine, hydroxyurea (HU), and methotrexate (MTX).
• Anti-mitotic agents disrupt the development of the mitotic spindle thereby interfering with tumor cell proliferation. Anti-mitotic agents include but are not limited to Vinblastine, Vincristine, and Pacitaxel (Taxol). Anti-mitotic agents also includes agents that target the enzymes that regulate mitosis, e.g., agents that target kinesin spindle protein (KSP), e.g., L-001000962-000Y.
5.9. KITS
• The invention provides kits that are useful in determining the stage of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.
• The invention provides kits that are useful in determining the progression of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 2a and/or 2b or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. In a preferred embodiment, the kits comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Table 4 or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.
• In one embodiment, the invention provides kits comprising probes that are immobilized at an addressable position on a substrate, e.g., in a microarray. In a particular embodiment, the invention provides such a microarray.
• The kits of the present invention may also contain probes that can be used to detect protein products of the marker genes of the invention. In a specific embodiment, the invention provides a kit comprises a plurality of antibodies that specifically bind a plurality of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 proteins that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 5a and/or 5b or functional equivalents of such genes, wherein the antibodies are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total antibodies in the kit. In accordance with this embodiment, the kit may comprise a set of antibodies or functional fragments or derivatives thereof (e.g., Fab, F(ab′)₂, Fv, or scFv fragments). In accordance with this embodiment, the kit may include antibodies, fragments or derivatives thereof (e.g., Fab, F(ab′)₂, Fv, or scFv fragments) that are specific for these proteins. In one embodiment, the antibodies may be detectably labeled.
• The kits of the present invention may also include reagents such as buffers, or other reagents that can be used in obtaining the marker profile. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like.
• In some embodiments of the invention, the kits of the present invention comprise a microarray. The microarray can be any of the microarrays described above, e.g., in Section 5.6.1, optionally in a sealed container. In one embodiment this microarray comprises a plurality of probe spots, wherein at least 20%, 40%, 60%, 80%, or 90% of the probe spots in the plurality of probe spots correspond to marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 4.
• In still other embodiments, the kits of the invention may further comprise a computer program product for use in conjunction with a computer system, wherein the computer program product comprises a computer readable storage medium and a computer program mechanism embedded therein. In such kits, the computer program mechanism comprises instructions for prediction of prognosis using a marker profile obtained with the reagents of the kits.
• In still other embodiments, the kits of the present invention comprise a computer having a central processing unit and a memory coupled to the central processing unit. The memory stores instructions for prediction of prognosis using a marker profile obtained with the reagents of the kits.
5.10. Pharmaceutical Formulations and Routes of Administration
• The compounds that can be used to modulate the expression of the CML progression genes or the activity of their gene products can be administered to a patient at therapeutically effective doses. A therapeutically effective dose refers to that amount of the compound sufficient to result in normal expression or activity level.
5.10.1. Effective Dose
• Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD₅₀(the dose lethal to 50% of the population) and the ED₅₀(the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD₅₀/ED₅₀. Compounds which exhibit large therapeutic indices are preferred. While compounds that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to uninfected cells and, thereby, reduce side effects.
• The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED₅₀with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC₅₀(i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.
5.10.2. Formulations and Use
• Pharmaceutical compositions for use in accordance with the present invention may be formulated in conventional manner using one or more pharmaceutically acceptable carriers or excipients.
• Thus, the compounds and their pharmaceutically acceptable salts and solvates may be formulated for administration by inhalation or insufflation (either through the mouth or the nose) or oral, buccal, parenteral or rectal administration.
• For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulphate). The tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g., methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.
• Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
• For buccal administration the compositions may take the form of tablets or lozenges formulated in conventional manner.
• For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g. gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
• The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.
• The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.
• In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
• The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration.
5.10.3. Routes of Administration
• Suitable routes of administration may, for example, include oral, rectal, transmucosal, transdermal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.
• Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into an affected area, often in a depot or sustained release formulation.
• Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with an antibody specific for affected cells. The liposomes will be targeted to and taken up selectively by the cells.
5.10.4. Packaging
• The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Compositions comprising a compound formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Suitable conditions indicated on the label may include treatment of a disease such as one characterized by aberrant or excessive expression or activity of a CML progression protein.
• 5.10.5. Combination Therapy
• In a combination therapy, one or more compositions of the present invention can be administered before, at the same time as, or after the administration of a chemotherapeutic agent. In one embodiment, the compositions of the invention are administered before the administration of an chemotherapeutic agent (i.e., the agent that modulates expression or activity of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein is for sequential or concurrent use with one or more chemotherapeutic agents). In one embodiment, the composition of the invention and a chemotherapeutic agent are administered in a sequence and within a time interval such that the composition of the invention and a chemotherapeutic agent can act together to provide an increased benefit than if they were administered alone. In another embodiment, the composition of the invention and a chemotherapeutic agent are administered sufficiently close in time so as to provide the desired therapeutic outcome. The time intervals between the administration of the compositions of the invention and a chemotherapeutic agent can be determined by routine experiments that are familiar to one skilled person in the art. In one embodiment, a chemotherapeutic agent is given to the patient after the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein reaches a desirable threshold. The level of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein can be determined by using any techniques known in the art such as those described in Section 5.3., infra.
• The composition of the invention and a chemotherapeutic agent can be administered simultaneously or separately, in any appropriate form and by any suitable route. In one embodiment, the composition of the invention and the chemotherapeutic agent are administered by different routes of administration. In an alternate embodiment, each is administered by the same route of administration. The composition of the invention and the chemotherapeutic agent can be administered at the same or different sites, e.g. arm and leg.
• In various embodiments, such as those described above, the composition of the invention and a chemotherapeutic agent are administered less than 1 hour apart, at about 1 hour apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 11 hours apart, 11 hours to 12 hours apart, no more than 24 hours apart or no more than 48 hours apart, or no more than 1 week or 2 weeks or 1 month or 3 months apart. As used herein, the word about means within 10%. In other embodiments, the composition of the invention and a chemotherapeutic agent are administered 2 to 4 days apart, 4 to 6 days apart, 1 week apart, 1 to 2 weeks apart, 2 to 4 weeks apart, one month apart, 1 to 2 months apart, or 2 or more months apart. In preferred embodiments, the composition of the invention and a chemotherapeutic agent are administered in a time frame where both are still active. One skilled in the art would be able to determine such a time frame by determining the half life of each administered component. In separate or in the foregoing embodiments, the composition of the invention and a chemotherapeutic agent are administered less than 2 weeks, one month, six months, 1 year or 5 years apart.
• In another embodiment, the compositions of the invention are administered at the same time or at the same patient visit, as the chemotherapeutic agent.
• In still another embodiment, one or more of the compositions of the invention are administered both before and after the administration of a chemotherapeutic agent. Such administration can be beneficial especially when the chemotherapeutic agent has a longer half life than that of the one or more of the compositions of the invention used in the treatment.
• In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 4 weeks, and then once every other week thereafter. In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 8 weeks, and then once every other week thereafter.
• In certain embodiments, the composition of the invention and the chemotherapeutic agent are cyclically administered to a subject. Cycling therapy involves the administration of the composition of the invention for a period of time, followed by the administration of a chemotherapeutic agent for a period of time and repeating this sequential administration. Cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment. In such embodiments, the invention contemplates the alternating administration of the composition of the invention followed by the administration of achemotherapeutic agent 4 to 6 days later, preferable 2 to 4 days, later, more preferably 1 to 2 days later, wherein such a cycle may be repeated as many times as desired.
• In certain embodiments, the composition of the invention and a chemotherapeutic agent are alternately administered in a cycle of less than 3 weeks, once every two weeks, once every 10 days or once every week. In a specific embodiment of the invention, one cycle can comprise the administration of a chemotherapeutic agent by infusion over 90 minutes every cycle, 1 hour every cycle, or 45 minutes every cycle. Each cycle can comprise at least 1 week of rest, at least 2 weeks of rest, at least 3 weeks of rest. In an embodiment, the number of cycles administered is from 1 to 12 cycles, more typically from 2 to 10 cycles, and more typically from 2 to 8 cycles.
• It will be apparent to one skilled person in the art that any combination of different timing of the administration of the compositions of the invention and a chemotherapeutic agent can be used. For example, when the chemotherapeutic agent has a longer half life than that of the composition of the invention, it is preferable to administer the compositions of the invention before and after the administration of the chemotherapeutic agent.
• The frequency or intervals of administration of the compositions of the invention depends on the desired level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein, which can be determined by any of the techniques known in the art, e.g., those techniques described infra. The administration frequency of the compositions of the invention can be increased or decreased when the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein changes either higher or lower from the desired level.
5.11. Implementation Systems and Methods
• The analytical methods of the present invention can preferably be implemented using a computer system, such as the computer system described in this section, according to the following programs and methods. Such a computer system can also preferably store and manipulate measured signals obtained in various experiments that can be used by a computer system implemented with the analytical methods of this invention. Accordingly, such computer systems are also considered part of the present invention.
• An exemplary computer system suitable from implementing the analytic methods of this invention is illustrated inFIG. 8. Computer system801 is illustrated here as comprising internal components and as being linked to external components. The internal components of this computer system include one ormore processor elements802 interconnected with amain memory803. For example, computer system801 can be an Intel Pentium IV®-based processor of 2 GHZ or greater clock rate and with 256 MB or more main memory. In a preferred embodiment, computer system801 is a cluster of a plurality of computers comprising a head “node” and eight sibling “nodes,” with each node having a central processing unit (“CPU”). In addition, the cluster also comprises at least 128 MB of random access memory (“RAM”) on the head node and at least 256 MB of RAM on each of the eight sibling nodes. Therefore, the computer systems of the present invention are not limited to those consisting of a single memory unit or a single processor unit.
• The external components can include amass storage804. This mass storage can be one or more hard disks that are typically packaged together with the processor and memory. Such hard disk are typically of 10 GB or greater storage capacity and more preferably have at least 40 GB of storage capacity. For example, in a preferred embodiment, described above, wherein a computer system of the invention comprises several nodes, each node can have its own hard drive. The head node preferably has a hard drive with at least 10 GB of storage capacity whereas each sibling node preferably has a hard drive with at least 40 GB of storage capacity. A computer system of the invention can further comprise other mass storage units including, for example, one or more floppy drives, one more CD-ROM drives, one or more DVD drives or one or more DAT drives.
• Other external components typically include a user interface device805, which is most typically a monitor and a keyboard together with a graphical input device806 such as a “mouse.” The computer system is also typically linked to anetwork link807 which can be, e.g., part of a local area network (“LAN”) to other, local computer systems and/or part of a wide area network (“WAN”), such as the Internet, that is connected to other, remote computer systems. For example, in the preferred embodiment, discussed above, wherein the computer system comprises a plurality of nodes, each node is preferably connected to a network, preferably an NFS network, so that the nodes of the computer system communicate with each other and, optionally, with other computer systems by means of the network and can thereby share data and processing tasks with one another.
• Loaded into memory during operation of such a computer system are several software components that are also shown schematically inFIG. 8. The software components comprise both software components that are standard in the art and components that are special to the present invention. These software components are typically stored on mass storage such as thehard drive804, but can be stored on other computer readable media as well including, for example, one or more floppy disks, one or more CD-ROMs, one or more DVDs or one or more DATs. Software component810 represents an operating system which is responsible for managing the computer system and its network interconnections. The operating system can be, for example, of the Microsoft Windows™ family such as Windows 95, Window 98, Windows NT,Windows 2000 or Windows XP. Alternatively, the operating software can be a Macintosh operating system, a UNIX operating system or a LINUX operating system. Software components811 comprises common languages and functions that are preferably present in the system to assist programs implementing methods specific to the present invention. Languages that can be used to program the analytic methods of the invention include, for example, C and C++, FORTRAN, PERL, HTML, JAVA, and any of the UNIX or LINUX shell command languages such as C shell script language. The methods of the invention can also be programmed or modeled in mathematical software packages that allow symbolic entry of equations and high-level specification of processing, including specific algorithms to be used, thereby freeing a user of the need to procedurally program individual equations and algorithms. Such packages include, e.g., Matlab from Mathworks (Natick, Mass.), Mathematica from Wolfram Research (Champaign, Ill.) or S-Plus from MathSoft (Seattle, Wash.).
• Software component812 comprises any analytic methods of the present invention described supra, preferably programmed in a procedural language or symbolic package. For example, software component812 preferably includes programs that cause the processor to implement steps of accepting a plurality of measured signals and storing the measured signals in the memory. For example, the computer system can accept measured signals that are manually entered by a user (e.g., by means of the user interface). More preferably, however, the programs cause the computer system to retrieve measured signals from a database. Such a database can be stored on a mass storage (e.g., a hard drive) or other computer readable medium and loaded into the memory of the computer, or the compendium can be accessed by the computer system by means of thenetwork807.
• In addition to the exemplary program structures and computer systems described herein, other, alternative program structures and computer systems will be readily apparent to the skilled artisan. Such alternative systems, which do not depart from the above described computer system and programs structures either in spirit or in scope, are therefore intended to be comprehended within the accompanying claims.
6. EXAMPLES
• The following examples are presented by way of illustration of the present invention, and are not intended to limit the present invention in any way.
6.1. Identification of Phase-Specific Genes in CML
• A set of 91 individual cases of CML, including chronic phase (N=42), accelerated phase by blast count criteria (N=9) or by the occurrence of additional clonal cytogenetic changes (N=8), blast crisis (N=28), and 4 cases of blast crisis in remission after chemotherapy were used to identify genes involved in progression from chronic phase to advanced disease (i.e., accelerated and blast phases). A pool of 200 chronic phase bone marrows was used as the reference. An ANOVA analysis revealed ˜3,000 genes differentially expressed across the different phases of disease using a minimum statistical significance cutoff of p<10⁻¹¹(Tables 1a and 1b). Sequences of polynucleotide probes used to detect these genes are listed in Table 8. This set of genes identified in the progression from chronic to blast phase is referred to here as the “phase reporter” gene set.FIG. 1 shows a “heat map” of the expression of the 3,000 phase reporter genes across the various phases of CML. This illustrates the global change of gene expression as the disease progresses from the chronic phase through the advanced phase of the disease.
• The expression patterns were then examined to determine if progression of CML best fits a three-step model as often described in the literature (chronic phase to accelerated phase to blast crisis), or a two-step model (chronic phase to advanced phase, i.e., accelerated or blast phase). The gene expression patterns of accelerated phase cases were compared to those of the blast crisis cases (FIG. 5). The correlation between the expression profiles of accelerated cases and those of the blast phase was quite strong (r=0.81). Comparing differentially regulated genes between accelerated phase with blast phase, there are very few phase specific genes, i.e. genes only regulated in one phase but not in another. These observations suggest that the difference of gene expression changes between accelerated and blast phase is a quantitative one rather than a qualitative one that requires new gene expression or repression.
• The biological functions of the genes associated with CML phases were also examined by applying a biological annotation program based on the GO and KEGG annotations. The functional groups most highly correlated with progression to blast crisis included increased expression of nuclear genes, mitochondrial genes, RNA binding genes, protein biosynthesis genes, and genes involved in chaperone function, all reflecting the increased proliferation and metabolism of progressive disease.
• Progression was also associated with decreases in the expression levels of genes involved in structural integrity and adhesion, as well as decreases in the expression levels of genes involved in inflammatory and immune response. In addition, several proto-oncogenes and tumor suppressor genes were differentially expressed with progression. For example, N- and Hras, FLT3, yes, AF1q, CBFB, WT1, ORALOV1, PTNN11, and Bc1-2 demonstrated increased expression in blast crisis as compared to chronic phase. Analysis of the phase reporter genes suggested a relative decrease in MAPPK signaling in advanced phase as compared to chronic phase. The progression was also seen as associated with increases in alternative signal pathways. Thus, the cytoplasmic GTP protein Rras2 was highly over-expressed in advanced phases, as was ras signaling components RAB56 and RALGD5. Alterations of cytokine signaling were demonstrated by an increase in expression of TNF factors SF4 and 7, and SOCS2 and 4.
6.2. Identification of Progression- and Response-Specific Genes
• Next, how the phase reporter gene set was influenced by the gene expression signature of leukemia blasts and how they compared to normal immature CD34+ cells were investigated. First, the gene expression signatures of eight samples of normal CD34+ cells were compared with CML blast samples containing >70% blasts (FIG. 2a). It was found that the gene expression pattern of CML blast cells was very similar to normal CD34+ cells, suggesting that “progression” from the chronic phase to the advanced phase is functionally similar to a block or “reversion” towards a more primitive hematopoetic cell. To uncover genes that are unique to progression, the normal CD34+ signatures were mathematically subtracted from each of the disease samples and the phase reporter signals were searched for (FIG. 2candFIG. 6). A set of 386 genes (p<10⁻⁸) were identified (FIG. 2cand Tables 2a and 2b). These genes are called the “progression genes.” A set of 368 genes with ANOVA p<0.1% were identified as differentially expressed between CML blast crisis and normal immature CD34+ cells were also identified (FIG. 2band Tables 5a and 5b). These genes are called the “target genes.” There were 103 genes overlapping between these two sets (hypergeometric P-value: 1.3×10⁻⁹⁹). This gene set is enriched in genes that are diagnostic markers of progression and novel targets of therapy. Table 3 shows the “top ten” genes that are associated with progression, independent of normal CD34+ expression, based onlog 10 ratio of expression compared to the chronic phase pool. These genes suggest a deregulation of genes of transcriptional regulation (GLI2, WT1, FOS, FOSB), signal transduction (SOCS2, Rras2, IL8), and apoptosis (GAS2). Moreover, twoHSP 70 subunits are differentially down-regulated, suggesting an alteration of this component of the chaperone system in blast crisis. Also significantly associated with progression was the surface protein PRAME, which has an unknown function, but has been associated with myeloid malignancy (van Baren et al. 1998, Br J Haematol 102:1376; Watari et al. 2000, FEBS Lett 466:367). Gene functions overrepresented in blast crisis were predominated by changes in ribosome gene expression and increased in the beta-catenin/WNT signaling pathway. More significant changes in gene function were down-regulated in progression, including nucleosome assembly and chromatin structure, sugar catabolism and metabolism, differentiation, and apoptosis.
6.3. Identification of Signaling Pathways Associated with Progression
• Multiple changes in several signaling pathways are represented in the progression gene set. Again, these genes were seen in the progression of chronic phase to advanced disease, but are differentially expressed compared to normal CD34+ cells. There was a deregulation of the betacatenin/WNT pathway. Expression of the cell surface protein cadherin was decreased, as was proto-cadhedrin, potentially leading to an activation of the beta-catenin/WNT signaling pathway by allowing more free beta-catenin to move to the cytoplasm. Moreover, the myogenesis transcription control gene MDFI (I-mfa), which complexes with axin (therefore potentially increasing free beta-catenin), was increased by approximately 7-fold. In all, 16 genes associated with the beta-catenin pathway were significantly over-expressed (e.g., PRICKLE1, CSNK1E, PLCB1, FZD2, LRP6, SMAD3, etc.). In summary, these findings strongly suggest aberrant activation of the betacatenin/WNT pathway during CML progression. Moreover, progression appears to be associated with a remodeling of several cytoskeletal and adhesion molecules, which may play a role in regulating proliferation. Thus there is an increase in CD47, Creb11, and ITGA5 expression, and a decrease in proto-cadhedrin, cadhedrin, actin, and betaactin.
• In addition, the abl family member abl2 (ARG) was significantly associated with disease progression; by contrast, abl1, which is both expressed from thenormal chromosome 9 and the t(9;22) translocation, was not differentially expressed with progression. Advanced phase disease was associated with deregulation of transcription factors, differentiation and apoptosis. Both components of the AP-1 transcription complex, Jun B and Fos, show decreased expression in progression. In addition, the Kupple-like zinc finger GLI2 is highly over-expressed in progression. The block in differentiation may be facilitated by the up-regulation of MDFI, WT1, and AF1q, and the down regulation of GADD45. Apoptosis in blast cells appears to be inhibited by the over-expression of Bcl2, DAP, and the decrease in MCL1 and Acinus. Progression was also associated with alterations in normal protein chaperone and degradation processes, with a widespread decrease in the expression of HSP70 and DNAJ families of genes. In addition, proteosome components BMA1 PSME2, and TRIP12 were all significantly increased in advanced phase CML cases.
6.4. Identification of Progression-Specific Promoters
• In order to examine if specific pathways were altered in progression, the progression and phase reporter gene sets were analyzed for aberrant expression of genes possessing known promoter sequences. Aberrant regulation of several sets of promoter controlled genes was revealed (Table 6). The most statistically significantly set of genes showing aberrant control in progression where those that contained a MZF promoter or a delta EF1 promoter sequence (p<10⁻¹⁵and <10⁻¹¹, respectively;FIGS. 3aand3b). Also significantly associated with progression were genes bearing SPI-B, Yin Yang, and Ahr-ARNT promoter sequences (all with p values <10⁻⁹).
6.5. Identification of Imatinib Responsiveness Reporter Genes
• Gene expression profiles of patients who failed imatinib therapy were analyzed. A set of 21 cases of CML treated with the tyrosine kinase inhibitor imatinib mesylate, including 9 patients who initially achieved a complete cytogenetic remission (CCR) on imatinib therapy, but then relapsed, most back into an apparent chronic phase by morphology; 3 cases who had achieved a complete hematologic but no cytogenetic response; 3 late chronic phase patients before treatment with imatinib; and 6 cases of blast crisis was used. All but one of these the chronic phase patients who relapsed after a CCR had a point mutation in abl1, presumably abrogating imatinib activity (Table 7).

• TABLE 7
  Characteristics of cases treated with imatinib

  		Phase of Disease at	Phase of disease at
  CODE	Case type	initiation of imatinib	time of sample	Cytogenetics	Mutation(s)
  2	Imatinib failure	chronic	relapsed chronic	100% Ph+;	M244V
  				NEW: t(1; 12) in all
  				cells
  4	Imatinib failure	chronic	relapsed chronic	100% Ph+	T315I
  5	Imatinib failure	chronic	relapsed chronic	80% Ph+	F359V
  6	Imatinib failure	chronic	relapsed chronic	100% Ph+	M351T,
  					F317L
  8	Imatinib failure	chronic	relapsed chronic	100% Ph+	M351T
  10	Imatinib failure	chronic	relapsed chronic	100% Ph+	E255K
  11	Imatinib failure	chronic post-allo	relapsed chronic	not available	T315I
  		BMT
  12	Imatinib failure	chronic	relapsed chronic	100% Ph+	L248V
  14	Imatinib failure	chronic	relapsed chronic	100% Ph+	M351T,
  					H396R
  15	Pre-imatinib	chronic	chronic pre-treatment	50% Ph+	none
  	treatment
  17	Pre-imatinib	chronic	chronic pre-treatment	100% Ph+	none
  	treatment
  18	Pre-imatinib	chronic	CHR; no cytogenetic	100% Ph+	none
  	treatment		response
  19	Pre-imatinib	chronic	chronic pre-treatment	45% t(9; 13; 22); 50%	none
  	treatment			t (9; 13; 22), −Y; 5%
  				nl
  21	Pre-imatinib	chronic	CHR; no cytogenetic	100% Ph+	none
  	treatment		response
  22 (same pt as	Pre-imatinib	chronic	CHR; no cytogenetic	100% Ph+ (3 of 18	none
  13)	treatment		response	with additional Ph)
  23	Pre-imatinib	myeloid blast crisis	pre-treatment MBC	100% Ph+	none
  	treatment
  24	Pre-imatinib	myeloid blast crisis	pre-treatment MBC	100% Ph+, t(2; 16)	none
  	treatment
  25	Pre-imatinib	myeloid blast crisis	pre-treatment MBC	100% Ph+, +8, iso	none
  	treatment			17q
  26	Pre-imatinib	myeloid blast crisis	not treated	not available	unknown
  	treatment
  27	Pre-imatinib	myeloid blast crisis	relapsed MBC	100% Ph+	unknown
  	treatment
  29	Pre-imatinib	myeloid blast crisis	relapsed MBC	not available	unknown
  	treatment
  29	Pre-imatinib	myeloid blast crisis	relapsed MBC	not available	unknown
  	treatment

• FIG. 4ashows the expression pattern of 15 cases of clinical chronic phase CML patients, 3 with longstanding chronic phase before imatinib treatment, the other 12 who had initially a suboptimal response (achieving only a hematological response) or relapsed after an initial CCR. The association with the progression signature can be demonstrated by segregating all CML cases by the correlation of gene expression signature between the boundaries of “most chronic” and “most advanced” gene expression for all 3,000 genes in the phase reporter gene set (FIG. 4b). The majority of the poor response patients had gene expression profiles more consistent with advanced disease rather than chronic phase. Both cases with T315I mutations, which have been shown to have especially poor prognosis, have expression signatures more similar to advanced disease than chronic phase. However, while these imatinib failures shared much of the blast crisis signature, there were gene expression features that were unique to these cases.FIG. 4ccompares relapsed imatinib cases against blast crisis cases. Several areas (boxed) indicate genes that are expressed in reverse direction in these two states. Table 4 lists genes in the first box which are strongly associated with imatinib failure. Examples of genes unique to imatinib failure are those of serine threonine kinases (CTRL, MAP21K14, CLK3), MAP kinase (MKNK2), and the tyrosine kinase oncogene FYN. The highest genes over-expressed in imatinib resistant cases were TCF7 (a putatively T cell specific transcription factor), two guanine nucleotide binding proteins (GNAZ and GNG11), and the MAF oncogene.
6.6. Discussion
• The biology and treatment of CML is dictated by the phase of disease, since the efficacy of all therapies (transplantation, interferon, imatinib) works best in chronic phase, and worse in accelerated phase and blast crisis. Understanding the biology of progression provides clinical diagnostic markers of progression, and offer insights into new strategies for treatment. The data presented in these examples suggest that the progression of chronic phase CML to advanced phase CML is a two-step process, with progression associated with a block of differentiation and apoptosis, a shift towards turning on expression of genes involved in the nucleosome, while down-regulating histone transcription. Moreover, progression is associated with alterations in cell adhesion, and activation of alternative signaling pathways. In addition, it appears that relapse after initial successful treatment with imatinib may be associated with gene expression patterns similar to advanced phase CML, suggesting that the process of progression persists in a subpopulation of CML cells even in the background of apparent successful therapy.
• The demonstration that the gene expression pattern between accelerated and blast phases are very similar suggests that the crucial steps in progression are at the transition of chronic to accelerated phase, before obvious morphologic, cytogenetic or clinical evidence of progression. This has obvious clinical implications, since these patients might benefit from aggressive therapy. In addition, the observation that gene signatures of blast crisis can be seen in accelerated phase patients by cytogenetic criteria only, and blast crisis cases in remission (both of which have low blast counts similar to patients with chronic phase disease), demonstrates two important points. First, it points out the difficulty of correlating morphology with the biology of the disease.
• Secondly, the penetration of a progression gene expression signature into a “chronic phase” appearing bone marrow suggests that progression is not merely an absolute block of differentiation, but that abnormal gene expression signals “leak” from the presumably immature blast crisis precursors into more normal appearing differentiated cell. This is critically important since it provides the basis for testing for progression genes in unsorted bone marrow samples from “chronic phase” patients.
• In addition, the finding that CML blasts share a gene expression profile with normal CD34+ cells has important biological considerations (Passegue et al., 2003, Proc NatlAcad Sci USA 100 Suppl 1:11842). First, it implies that there may be a limited number of novel pathways active in CML blasts. This finding is obviously important (and encouraging) in the era of targeted therapeutics. It also may explain the relative resistance of blast crisis CML to chemotherapy. Normal hematopoetic stem cells are remarkably resistant to chemotherapy, and thus in AML and ALL, with remission comes the return of normal hematopoiesis. Remission is rare in blast crisis CML, perhaps because the blast cells are similarly resistant to chemotherapy as their normal counterpart.
• Bcr-Ab1 has a wholesale range of biological activities. Critical in the transformation process is the activation of the Ras/MAPK pathways, which has broad effects on changes in cell adhesion (through Rho), proliferation (MAPK pathway), and apoptosis (through Akt) (Faderl et al., 1999, N Engl J Med 341:164; Ren, 2002, Oncogene 21:8629). The efficacy of imatinib works through the blockade of these effects.
• Imatinib works poorly on advanced phase disease, and it may be because these tumors are less reliant on the pathways that imatinib blocks than chronic phase disease. Thus, it was found that the MAPK pathway was relatively under-expressed in advanced disease compared to chronic phase, but other signaling pathways, including those involving cytokines (IL3RA, SOCS2), alternative ras pathways (Rras2), and those involved in cell adhesion (B-catenin/WNT) were activated. The activation of these pathways may allow progression even in the face of therapeutic blockade of Bcr-Ab1 activated pathways. In addition, abl2 (Ab1 related gene, or ARG) is also upregulated in progresson. As opposed to abl1 (which is a nuclear protein until involved in the chimeric Bcr-Ab1 protein, at which time it migrates to the cytoplasm), ARG is a cytoplasmic protein (Kruh et al., 1990, Proc Natl Acad Sci USA 87:5802). The signaling targets of ARG are unknown, and although broadly expressed in tissue, its only known functional role apparent from knockout mouse models appears to be in the nervous system (Koleske et al., 1998, Neuron 21:1259; Perego et al., 1991, Oncogene 6:1899). ARG has been associated with myeloid leukemia in the contest of TEL/ARG translocations (Cazzaniga et al., 1999, Blood 94:4370; Iijima et al., 2000, Blood 95:2126). ARG shares over 90% homology of its tyrosine kinase domain with abl1, and ARG tyrosine kinase activity is inhibited by imatinib at similar drug concentrations (Kruh et al., 1990, Proc Natl Acad Sci USA 87:5802; Okuda et al., 2001, Blood 97:2440). However, given that Bcr-ABL amplification is considered to play a role in imatinib resistance (le Coutre et al. 2000, Blood 95:1758; Weisberg et al., 2000, Blood 95:3498), ARG over-expression in blast crisis could theoretically contribute to the relative resistance to imatinib found with progressive disease.
• Two recent observations on the molecular biology of progression in CML are relevant to this study. First, activation of the beta-catenin pathway was observed in primary cell samples from patients with CML (Jamieson et al., 2004, N Engl J Med 351:657). Secondly, it was recently observed that mice deficient in Jun B develop a disease much like CML (Passegue et al., 2004, Cell 119:431). The data in these examples complement these findings, as we found broad dysregulation of WNT/beta-catenin pathway as well as decreased Jun B expression. A link between these pathways may be the gene MDFI (Imfa), an inhibitor of myogenic basic H-L-H transcription factors 4. MDFI interacts with axin, which is involved in binding and modulating free beta-catenin. Thus an increase in MDFI would effectively allow for more free beta-catenin to migrate to the nucleus, where it causes gene activation (Nelson et al., 2004, Science 303:1483). An increase in MDFI could also decrease the axinmediated activation of Jun (Kusano et al., 2002, Mol Cell Biol 22:6393). Thus, MDFI may play a central role in progression by both influencing the beta-catenin and Jun B pathways. Moreover, the fact that both Jun B and Fos were down-regulated in progression suggests that there may be a wholesale deregulation in AP-1 targets, which could have broad functional affects on differentiation, apoptosis, and cell cycle control (Hess et al., 2004, J Cell Sci 117:5965).
• The analysis suggests that genes controlled by MZF1 and delta EF1 may be particularly important in progression. MZF1 is a member of the Kruppel family of zinc finger proteins, and was originally cloned from a cDNA library from a blast crisis CML patient (Hromas et al., 1991, J Biol Chem 266:14183). MZF1 appears to play a critical role in hematopoetic stem cell differentiation, including modulation of CD34 and c-myb expression (Gaboli et al., 2001, Genes Dev 15:1625; Perrotti et al., 1995, Mol Cell Biol 15:6075). MZF1 −/− knock-out mice display an increase in hemapoetic progenitor proliferation which continues in long-term culture conditions (Gaboli et al., 2001, Genes Dev 15:1625). These data support the findings found in our human studies described about that MZF1 deregulation may disrupt normal differentiation, promoting the progression to advanced disease. Delta EF1 is related to the Smad zinc finger proteins that play an important role in TGFbeta gene regulation. Delta EF1 has been shown to compete with basic helix-loop-helix activators, and is implicated in modulation of MyoD regulated pathways (Funahashi et al., 1993, Development 119:433; Sekido et al., 1994, Mol Cell Biol 14:5692). It is not known if delta EF1 directly influences MDFI expression.
• Of note is that both MZF1 and delta EF1 have been shown to influence cadherin expression (Guaita et al., 2002, J Biol Chem 277:39209; Le et al., 2005, Exp Cell Res 302:129; Miyoshi et al., 2004, Br J Cancer 90:1265). Thus, the further study of the control of MZF1 and delta EF1 may be particularly fruitful in understanding the molecular mechanisms of CML progression. Given that efficacy of treatment in CML (be it with interferon, imatinib, or transplantation) is so intimately associated with phase of disease, those patients who fail therapy in chronic phase may have genetic features of advanced phase invisible to routine pathological and cytogenetic exam. Imatinib failures are a reasonable setting to explore this possibility. While imatinib can cause cytogenetic remissions in the majority of chronic phase cases, treatment failure, especially secondary to point mutations, is an increasingly important problem. It has previously been demonstrated that the probability of developing a point mutation depends largely on the time from diagnosis to initiation of therapy (Branford et al., 2003, Blood 102:276). This finding implies that the genetic mechanisms that lead to point mutations are relentless, and therefore the treatment of “late” chronic phase patients (i.e., >1 year from diagnosis) may be undermined by genetic changes that have already occurred. Branford et al. demonstrated that patients who developed point mutations had a very poor outcome, with approximately half dying within a year of relapse (Branford et al., 2003, Blood 102:276). These observations are in keeping with the demonstration in these examples that many imatinib failures have gene expression changes similar to advanced disease, despite their benign pathological appearance. Thus, resistance to imatinib may be ameliorated by either targeting pathways of progression (beta-catenin, JunB/Fos, etc.), or by targeting pathways specifically found activated in imatinib resistance cases (alternative kinases, protein transporters).
• Several of the genes found in the progression set might serve as early markers of progression in diagnostic assays, and may serve as therapeutic targets, as well. For example, PRAME (Preferentially Expressed Antigen of Melanoma) was originally identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). Like similar antigens MAGE, BAGE, and GAGE, which are expressed in some solid tumors; unlike these other antigens, however, PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). Indeed, PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729). While the function of PRAME is still unknown, its expression on the cell surface might be amenable to flow cytometry assays, as well as a target for immunologic (vaccine or cell-based) therapy. CD47, an integrin-like protein, is another potential diagnostic target discovered in our analysis of progression (Motegi et al., 2003, Embo J 22:2634; Okazawa et al., 2005, J Immunol 174:2004). In addition, the demonstration of aberrant regulation of alternative signaling pathways (FLT3; Rras2; beta-catenin. SOCS2), proteosomes, and chaperone proteins suggest that the targeting of several novel pathways may be needed in the treatment of advanced CML.
• Compared to other types of leukemia, there have been few papers exploring the use of microarrays on the biology of CML. In sum, 23 patients of various stages have been studied, 10 on unsorted samples, 13 from AC133+ isolated cells. It is difficult to make a direct comparison of these studies and ours, given the different types of samples obtained, the difference in the array platforms (these studies used platforms examining 3,000-5,000 genes, compared to ˜24,000 genes in this current study). In general, however, the functional changes of progression, e.g., changes in differentiation, apoptosis, and cell adhesion, remained as common themes across the study. In contrast to one study, no significant differences in signatures obtained from bone marrow and peripheral blood (FIG. 7) were found, which may be important in future prospective studies of this disease in patients.
• These findings have the potential to influence therapy of CML. Patients who present with gene expression patterns suggestive of advanced phase disease might benefit to move straight to transplantation if a donor exists, or if not, other investigation therapies. Moreover, PCR assays of individual genes (or small sets of genes) may be used to monitor patients early in the course of imatinib therapy for signs of progression to advanced disease. Microarray studies of large cohorts of patients treated with imatinib will likely identify gene patterns indicative of response that can be used immediately at diagnosis to tailor therapy.
6.7. Materials and Methods
• Patient samples. All samples were obtained under the auspices of institutional review board approve protocols. Samples came from the FHCRC, the Southwest Oncology Group (SWOG) Myeloid Repository, the University of Oregon Health Sciences Center, the University of California, Los Angeles, or the University of Chicago. RNA extraction was either performed immediately, or in the case of samples stored in a liquid nitrogen repository, after thawing. All RNA samples were quality tested by analysis of ribosomal RNA peaks using an ABI Bioalyzer. The definition of chronic, accelerated and blast crisis was based on the criteria of Sokal (Sokal et al., 1984, Blood 63:789).
• Amplification, labeling, and hybridization. The procedures of RNA amplification, labeling, and the hybridization to arrays, as well as the specifics of the array platforms, has been previously published (Hughes et al., 2001, Nat Biotechnol 19:342).
• Analytic Methods and Results. Each individual sample was hybridized to a pool of chronic phase samples. The log10 (Ratio) of intensity of individual samples to the pool were used for the subsequent analysis. Before selecting features by ANOVA, 25,000 genes on the array were first screened for evidence of differential regulation by requiring P-value of regulation <1% in more than 3 experiments. Where P-value of regulation is based on the platform error model. Features differentiating progression stages were selected by ANOVA test.
• Functional annotation of gene lists. Genes represented on the microarray were annotated by assignment to GO Biological Process or Molecular Function categories (at the web address www.ebi.ac.uk/GOA/), or to KEGG pathways (at the web address www.genome.jp/kegg/pathway.html). Gene lists (input sets) were queried for enrichment of members of specific functional classes or pathways relative to the background frequency. The significance (P-value) of enrichment was computed using the hypergeometric probability distribution. Reported in each case are the numbers of genes in the input set (input gene count), number of genes in a particular category or pathway in the input set (overlap gene count), number of genes in a particular category among all genes present on the array (set gene count). The total number of unique genes on the array is 24132.
• Methods to common promote site analysis. The common promoter sites were based on the predictions derived from the database (oPOSSUM) by Wasserman et al. (www.cisreg.ca). The hypergeometric P-value for enrichment of a particular binding site was computed by comparing the number of genes with the binding site from a signature gene set to that from a background set (i.e., all genes represented on the microarray).
• Controls. We compared the genes found associated with progression to the genes found significantly over- and under-expressed with prolonged “transit time” from sample acquisition to RNA processing (Radich et al., 2004, Genomics 83:980). There gene signatures of the two data sets were different, excluding this artifact as contributing significantly to the progression gene set.
• Lastly, we compared gene expression signatures from the sites contributing samples to confirm that there were no site-signatures confounding the analysis. We found no evidence of site-specific signatures.
• As some samples of blast crisis came from peripheral blood rather than bone marrow, we compared three samples in which simultaneous samples were available from bone marrow and peripheral blood. Gene expression was extremely well correlated (r=0.97 to 0.99;FIG. 7).

• TABLE 8
  The phase reporter genes

  				SEQ	PROBE SEQ
  SUBS	GENE	DESCRIPTION	SP_XREF_KEYWORD_LIST	ID NO.	ID NO.

  AB002301	KIAA0303	KIAA0303 protein	Hypothetical protein, ATP-binding,	1	3969
  			Kinase, Serine/threonine-protein
  			kinase, Transferase
  AB002313	PLXNB2	plexin B2	Hypothetical protein	2	3970
  AB002314	KIAA0316	KIAA0316 gene	Hypothetical protein	3	3971
  		product
  AB002331	DATF1	death associated	Apoptosis, Nuclear protein, Zinc-	4	3972
  		transcription factor 1	finger, Alternative splicing
  AB002336	EPB41L1	erythrocyte	Hypothetical protein, Structural	5	3973
  		membrane protein	protein, Cytoskeleton, Actin-binding
  		band 4.1-like 1
  AB002337	KIAA0339	KIAA0339 gene	Hypothetical protein	6	3974
  		product
  AB002354	KIAA0356	pleckstrin homology	Hypothetical protein	7	3975
  		domain containing,
  		family M (with RUN
  		domain)member 1
  AB002359	PFAS	phosphoribosylformylglycinamidine	Purine biosynthesis, Ligase, ATP-	8	3976
  		synthase (FGAR	binding, Glutamine
  		amidotransferase)	amidotransferase, Hypothetical
  			protein
  AB002360	MCF2L	MCF.2 cell line	Hypothetical protein, Guanine-	9	3977
  		derived transforming	nucleotide releasing factor, Proto-
  		sequence-like	oncogene
  AB002366	KIAA0368	KIAA0368	Hypothetical protein	10	3978
  AB002368	XPO6	exportin 6	Hypothetical protein	11	3979
  AB002369	MTMR3	myotubularin related	Hydrolase, Zinc-finger, Alternative	12	3980
  		protein 3	splicing, Hypothetical protein
  AB002373	KIAA0375	RUN and SH3	Hypothetical protein,SH3 domain	13	3981
  		domain containing 2
  AB002377	KIAA0379	ankyrin repeat	Hypothetical protein, Repeat, ANK	14	3982
  		domain 28	repeat
  AB002379	DAAM2	dishevelled	Coiled coil,Alternative splicing	15	3983
  		associated activator
  		ofmorphogenesis 2
  AB004857	SLC11A2	solute carrier family	Transport, Iron transport,	16	3984
  		11 (proton-coupled	Transmembrane, Glycoprotein,
  		divalent metal ion	Alternative splicing, Polymorphism
  		transporters),
  		member 2
  AB006622	KIAA0284	KIAA0284	Hypothetical protein	17	3985
  AB007855	TIX1	zinc fingers and	DNA-binding, Homeobox, Nuclear	18	3986
  		homeoboxes 3	protein, Zinc-finger, Metal-binding,
  			Repeat
  AB007863	PIP3-E	phosphoinositide-	Hypothetical protein	19	3987
  		binding protein PIP3-E
  AB007864	KIAA0404	KIAA0404 protein	Hypothetical protein, Metal-binding,	20	3988
  			Oxidoreductase, Zinc
  AB007888	MBNL1	muscleblind-like	Hypothetical protein, Zinc-finger,	21	3989
  		(Drosophila)	Repeat, Nuclear protein, RNA-
  			binding, Alternative splicing
  AB007902	AUTS2	autism susceptibility	Chromosomal translocation,	22	3990
  		candidate 2	Polymorphism, Alternative splicing
  AB007915	KIAA0446	KIAA0446 gene	Hypothetical protein	23	3991
  		product
  AB007931	RBAF600	retinoblastoma-	Hypothetical protein	24	3992
  		associatedfactor
  		600
  AB007941	KIAA0472	dusty protein kinase	ATP-binding, Transferase,	25	3993
  			Hypothetical protein, Kinase,
  			Serine/threonine-protein kinase
  AB007958	KIAA0489	KIAA0792 gene	Hypothetical protein	26	3994
  		product
  AB007962	KIAA0493	KIAA0493 protein		27	3995
  AB007965	CYHR1	MRNA, chromosome		28	3996
  		1 specific transcript
  		KIAA0496.
  AB007972	PPP1R12B	protein phosphatase	ANK repeat, Myosin, Repeat	29	3997
  		1, regulatory
  		(inhibitor) subunit
  		12B
  AB011093	P114-RHO-	rho/rac guanine	Hypothetical protein	30	3998
  	GEF	nucleotide exchange
  		factor (GEF) 18
  AB011105	LAMA5	laminin,alpha 5	Laminin EGF-like domain, Signal,	31	3999
  			Glycoprotein, Basement membrane,
  			Extracellular matrix, Coiled coil, Cell
  			adhesion, Repeat
  AB011112	KIAA0540	KIAA0540 protein	Hypothetical protein, Repeat, WD	32	4000
  			repeat
  AB011114	KIAA0542	KIAA0542 gene	Hypothetical protein	33	4001
  		product
  AB011133	KIAA0561	microtubule	Hypothetical protein, ATP-binding,	34	4002
  		associated	Kinase, Serine/threonine-protein
  		serine/threonine	kinase, Transferase
  		kinase 3
  AB011136	KIAA0564	KIAA0564 protein	Hypothetical protein, ATP-binding	35	4003
  AB011153	PLCB1	phospholipase C,	Hydrolase, Lipid degradation,	36	4004
  		beta 1	Transducer, Phosphorylation,
  		(phosphoinositide-	Calcium, Alternative splicing
  		specific)
  AB011154	RAB1A	KIAA0582 protein	Hypothetical protein	37	4005
  AB011157	PTDSR	phosphatidylserine	Hypothetical protein,Receptor	38	4006
  		receptor
  AB011167	KIAA0595	peroxisome	Hypothetical protein	39	4007
  		proliferative
  		activated receptor,
  		gamma, coactivator-
  		related 1
  AB011171	KIAA0599	KIAA0599	Hypothetical protein, Plasmid	40	4008
  AB011173	KIAA0601	amine oxidase	Hypothetical protein	41	4009
  		(flavin containing)
  		domain 2
  AB011542	EGFL5	EGF-like-domain,	Laminin EGF-like domain	42	4010
  		multiple 5
  AB012692	CAC-1	beta-casein-like	Hypothetical protein	43	4011
  		protein
  AB014516	MECT1	Homo sapiens	Transcription regulation, DNA-	44	4012
  		mRNA for KIAA0616	binding, Activator, Nuclear protein,
  		protein, partial cds.	Phosphorylation, Cell cycle,
  			Alternative splicing, 3D-structure,
  			Polymorphism, Hypothetical protein
  AB014520	PLXND1	plexin D1	Hypothetical protein	45	4013
  AB014538	KIAA0638	pleckstrin homology-	Hypothetical protein	46	4014
  		like domain, family
  		B, member 1
  AB014543	KIAA0643	KIAA0643 protein	Hypothetical protein	47	4015
  AB014548	KIAA0648	KIAA0648 protein	Hypothetical protein	48	4016
  AB014557	KIAA0657	KIAA0657 protein	Hypothetical protein,	49	4017
  			Immunoglobulin domain
  AB014558	CRY2	cryptochrome 2	Lyase, Hypothetical protein	50	4018
  		(photolyase-like)
  AB014564	KIAA0664	KIAA0664 protein	Hypothetical protein, Initiation factor,	51	4019
  			Protein biosynthesis
  AB014566	DAAM1	dishevelled	Coiled coil, Alternative splicing	52	4020
  		associated activator
  		of morphogenesis 1
  AB014567	TIP120B	TBP-interacting	Hypothetical protein	53	4021
  		protein
  AB014568	UNC84B	unc-84 homolog B	Transmembrane, Nuclear protein,	54	4022
  		(C. elegans)	Coiled coil
  AB014574	KIAA0674	KIAA0674 protein	Hypothetical protein	55	4023
  AB014578	KIAA0678	RME8 protein	Hypothetical protein	56	4024
  AB014589	CSTF2T	cleavage stimulation	Hypothetical protein	57	4025
  		factor, 3′ pre-RNA,
  		subunit 2, 64 kDa,
  		tau variant
  AB014597	GTAR	ankyrin repeat	Hypothetical protein, ANK repeat,	58	4026
  		domain 17	Repeat
  AB014600	SIN3B	SIN3 homolog B,	Transcription regulation, Repressor,	59	4027
  		transcriptional	Repeat, Nuclear protein
  		regulator (yeast)
  AB014604	OSBPL3	oxysterol binding	Lipid transport, Transport,	60	4028
  		protein-like 3	Alternative splicing
  AB015330	DKFZP761I2123	hypothetical protein	Hypothetical protein	61	4029
  		DKFZp761I2123
  AB015343	HRIHFB2122	Tara-like protein	Cytoskeleton, Actin-binding, Coiled	62	4030
  			coil, Nuclear protein
  AB018268	KIAA0725	SAM, WWE and	Hypothetical protein	63	4031
  		DDHD domain
  		containing 1
  AB018325	CENTD2	centaurin, delta 2	GTPase activation, Repeat, Zinc-	64	4032
  			finger, Alternative splicing
  AB018339	SYNE1	spectrin repeat	Structural protein, Cytoskeleton,	65	4033
  		containing, nuclear	Actin-binding, Coiled coil,
  		envelope 1	Transmembrane, Repeat, Alternative
  			splicing, Polymorphism
  AB018348	PCNX	pecanex homolog	Transmembrane, Glycoprotein,	66	4034
  		(Drosophila)	Alternative splicing
  AB018353	UNC84A	unc-84 homolog A	Transmembrane, Nuclear protein,	67	4035
  		(C. elegans)	Coiled coil, Alternative splicing
  AB020627	KIAA0820	dynamin family	Hydrolase, Motor protein, GTP-	68	4036
  		member	binding, Microtubule, Multigene
  			family, Endocytosis
  AB020636	TIP120A	TBP-interacting	Hypothetical protein	69	4037
  		protein
  AB020637	KIAA0830	KIAA0830 protein	Hypothetical protein	70	4038
  AB020644	FACL6	acyl-CoA synthetase	Ligase, Fatty acid metabolism,	71	4039
  		long-chain family	Magnesium, Multigene family,
  		member 6	Alternative splicing, Chromosomal
  			translocation, Hypothetical protein
  AB020649	KIAA0842	pleckstrin homology	Hypothetical protein	72	4040
  		domain containing,
  		family M (with RUN
  		domain) member 2
  AB020673	MYH11	myosin, heavy	Myosin, Muscle protein, Coiled coil,	73	4041
  		polypeptide 11,	Thick filament, Actin-binding,
  		smooth muscle	Calmodulin-binding, ATP-binding,
  			Methylation, Multigene family, Proto-
  			oncogene, Chromosomal
  			translocation
  AB020684	KIAA0877	KIAA0877 protein	Hypothetical protein	74	4042
  AB020691	KIAA0884	GTPase activating	Hypothetical protein	75	4043
  		RANGAP domain-
  		like 1
  AB020695	KIAA0888	KIAA0888 protein	Hypothetical protein	76	4044
  AB020698	USP19	ubiquitin specific	Protease, Ubl conjugation pathway,	77	4045
  		protease 19	Hydrolase, Thiol protease, Multigene
  			family, Zinc-finger, Metal-binding
  AB020703	DD5	progestin induced	Ubl conjugation pathway, Ligase,	78	4046
  		protein	Nuclear protein, 3D-structure
  AB020704	PPFIA4	protein tyrosine	Hypothetical protein	79	4047
  		phosphatase,
  		receptor type, f
  		polypeptide
  		(PTPRF), interacting
  		protein (liprin), alpha 4
  AB023152	KIAA0935	mannosidase alpha	Hydrolase, Glycosidase, Signal,	80	4048
  		class 2B member 2	Glycoprotein, Hypothetical protein
  AB023154	KIAA0937	macrophage	Hypothetical protein, Metal-binding,	81	4049
  		expressed gene 1	Zinc, Zinc-finger
  AB023156	SLC9A8	solute carrier family	Hypothetical protein	82	4050
  		9 (sodium/hydrogen
  		exchanger), isoform 8
  AB023164	KIAA0947	KIAA0947 protein	Hypothetical protein	83	4051
  AB023210	WDFY3	WD repeat and	Hypothetical protein, Repeat, WD	84	4052
  		FYVE domain	repeat
  		containing 3
  AB023211	PADI2	peptidyl arginine	Hydrolase, Calcium-binding,	85	4053
  		deiminase, type II	Multigene family
  AB023212	PCNX	pecanex homolog	Transmembrane, Glycoprotein,	86	4054
  		(Drosophila)	Alternative splicing
  AB023216	KIAA0999	KIAA0999 protein	Hypothetical protein, ATP-binding,	87	4055
  			Kinase, Serine/threonine-protein
  			kinase, Transferase
  AB023230	KIAA1013	GRP1-binding	Hypothetical protein, Cytoskeleton	88	4056
  		protein GRSP1
  AB023233	CHDC1	calponin homology	Hypothetical protein, Leucine-rich	89	4057
  		(CH) domain	repeat, Repeat
  		containing 1
  AB025254	PCTAIRE2BP	tudor repeat	Hypothetical protein	90	4058
  		associator with
  		PCTAIRE 2
  AB026054	ZNF179	zinc finger protein	Zinc-finger	91	4059
  		179
  AB026436	DUSP10	dual specificity	Hydrolase, Nuclear protein,	92	4060
  		phosphatase 10	Hypothetical protein
  AB028972	KIAA1049	KIAA1049 protein	Hypothetical protein	93	4061
  AB028978	KIAA1055	KIAA1055 protein	Hypothetical protein	94	4062
  AB028980	USP24	ubiquitin specific	Hypothetical protein, Ubl conjugation	95	4063
  		protease 24	pathway, Hydrolase, Thiol protease,
  			Multigene family
  AB028986	USP22	ubiquitin specific	Hypothetical protein, Protease, Ubl	96	4064
  		protease 22	conjugation pathway, Hydrolase,
  			Thiol protease, Multigene family
  AB028989	MAPK8IP3	mitogen-activated	Phosphorylation, Coiled coil	97	4065
  		protein kinase 8
  		interacting protein 3
  AB028994	AMOT	angiomotin	Hypothetical protein	98	4066
  AB029030	KIAA1107	KIAA1107 protein	Hypothetical protein	99	4067
  AB029032	FLJ21404	hypothetical protein	Hypothetical protein	100	4068
  		KIAA1109
  AB029041	KIAA1118	likely ortholog of	Hypothetical protein	101	4069
  		mouse 5-azacytidine
  		induced gene 1
  AB032952	KIAA1126	KIAA1126 protein	Hypothetical protein	102	4070
  AB032965	CASKIN2	CASK interacting	Hypothetical protein, ANK repeat,	103	4071
  		protein 2	Repeat
  AB032973	LCHN	LCHN protein	Hypothetical protein	104	4072
  AB032976	P66	transcription	Hypothetical protein	105	4073
  		repressor p66 beta
  		component of the
  		MeCP1 complex
  AB032993	GRIPAP1	GRIP1 associated	Hypothetical protein	106	4074
  		protein 1
  AB033009	KIAA1183	KIAA1183 protein	Hypothetical protein	107	4075
  AB033037	KIAA1211	KIAA1211 protein	Hypothetical protein	108	4076
  AB033050	RAI17	retinoic acid induced	Hypothetical protein	109	4077
  		17
  AB033053	ZNF295	zinc finger protein	Transcription regulation, DNA-	110	4078
  		295	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  AB033055	KIAA1229	KIAA1229 protein	Hypothetical protein	111	4079
  AB033068	FZR1	Fzr1 protein	Hypothetical protein, Ubl conjugation	112	4080
  			pathway, Cell cycle, Cell division,
  			Mitosis, Repeat, WD repeat,
  			Phosphorylation, Alternative splicing
  AB033070	KIAA1244	KIAA1244	Hypothetical protein	113	4081
  AB033073	KIAA1247	sulfatase 2	Hydrolase, Signal, Glycoprotein,	114	4082
  			Endoplasmic reticulum, Golgi stack
  AB033085	KIAA1259	hypothetical protein	Hypothetical protein, ATP-binding,	115	4083
  		KIAA1259	Helicase, Hydrolase
  AB033087	TLE4	transducin-like	Transcription regulation, Repressor,	116	4084
  		enhancer of split 4	Nuclear protein, Repeat, WD repeat,
  		(E(sp1) homolog,	Phosphorylation, Wnt signaling
  		Drosophila)	pathway
  AB033091	KIAA1265	solute carrier family	Hypothetical protein	117	4085
  		39 (zinc transporter),
  		member 10
  AB033092	MTA3	metastasis	Hypothetical protein, Zinc-finger,	118	4086
  		associated family,	Nuclear protein, Alternative splicing
  		member 3
  AB033100	KIAA1274	KIAA protein (similar	Hypothetical protein	119	4087
  		to mouse paladin)
  AB033108	KCNH3	potassium voltage-	Hypothetical protein, Transport, Ion	120	4088
  		gated channel,	transport, Ionic channel, Voltage-
  		subfamily H (eag-	gated channel, Potassium channel,
  		related), member 3	Potassium transport,
  			Transmembrane, Glycoprotein,
  			Multigene family
  AB033112	BRPF3	bromodomain and	Hypothetical protein, Zinc-finger,	121	4089
  		PHD finger	Bromodomain
  		containing, 3
  AB033118	ZDHHC8	zinc finger, DHHC	Transmembrane, Zinc-finger,	122	4090
  		domain containing 8	Hypothetical protein
  AB037716	KIAA1295	KIAA1295 protein	Hypothetical protein, SH3 domain	123	4091
  AB037720	SH2B	SH2-B homolog	Hypothetical protein	124	4092
  AB037721	STARD9	START domain	Hypothetical protein	125	4093
  		containing 9
  AB037722	KIAA1301	NEDD4-related E3	Hypothetical protein	126	4094
  		ubiquitin ligase
  		NEDL2
  AB037729	RALGDS	ral guanine	Guanine-nucleotide releasing factor,	127	4095
  		nucleotide	3D-structure, Hypothetical protein
  		dissociation
  		stimulator
  AB037749	KIAA1328	KIAA1328 protein	Hypothetical protein	128	4096
  AB037757	KIAA1336	WD repeat domain	Hypothetical protein, Repeat, WD	129	4097
  		35	repeat
  AB037760	ZNF398	zinc finger protein	Transcription regulation, Activator,	130	4098
  		398	DNA-binding, Zinc-finger, Metal-
  			binding, Nuclear protein, Repeat,
  			Alternative splicing
  AB037771	KIAA1350	ubiquitin specific	Hypothetical protein	131	4099
  		protease 53
  AB037787	NLGN2	neuroligin 2	Cell adhesion, Glycoprotein, Signal,	132	4100
  			Transmembrane
  AB037795	KIAA1374	KIAA1374 protein	Hypothetical protein, Repeat, WD	133	4101
  			repeat
  AB037802	COG1	component of	Transport, Protein transport, Golgi	134	4102
  		oligomeric golgi	stack, Membrane
  		complex 1
  AB037813	DKFZp762K222	hypothetical protein	Hypothetical protein	135	4103
  		DKFZp762K222
  AB037814	KIAA1393	KIAA1393	Hypothetical protein	136	4104
  AB037836	PRex1	phosphatidylinositol	Guanine-nucleotide releasing factor,	137	4105
  		3,4,5-trisphosphate-	Repeat, Alternative splicing
  		dependent RAC
  		exchanger 1
  AB037845	ARHGAP10	Rho GTPase	Hypothetical protein	138	4106
  		activating protein 21
  AB037851	KIAA1430	KIAA1430 protein	Hypothetical protein	139	4107
  AB037855	KIAA1434	hypothetical protein	Hypothetical protein	140	4108
  		KIAA1434
  AB037859	MKL1	megakaryoblastic	Transcription regulation, Nuclear	141	4109
  		leukemia	protein, Coiled coil, Repeat,
  		(translocation) 1	Chromosomal translocation, Proto-
  			oncogene
  AB037860	NFIA	nuclear factor I/A	Activator, DNA replication, DNA-	142	4110
  			binding, Nuclear protein,
  			Transcription, Transcription
  			regulation, Multigene family
  AB037861	DKFZP586J0619	DKFZP586J0619	Hypothetical protein	143	4111
  		protein
  AB040881	KIF1B	kinesin family	Hypothetical protein, Motor protein,	144	4112
  		member 1B	Microtubule, ATP-binding, Coiled
  			coil, Mitochondrion, Alternative
  			splicing, Disease mutation, Charcot-
  			Marie-Tooth disease
  AB040900	KIAA1467	KIAA1467 protein	Hypothetical protein	145	4113
  AB040907	KIAA1474	zinc finger protein	Hypothetical protein, Metal-binding,	146	4114
  		537	Zinc, Zinc-finger
  AB040908	VPS18	vacuolar protein	Transport, Protein transport,	147	4115
  		sorting protein 18	Membrane, Zinc-finger, Coiled coil,
  			Alternative splicing
  AB040917	KIAA1484	leucine rich repeat	Hypothetical protein,	148	4116
  		and fibronectin type	Immunoglobulin domain
  		III domain containing 1
  AB040930	LRRN1	leucine rich repeat	Hypothetical protein,	149	4117
  		neuronal 1	Immunoglobulin domain
  AB040942	KIAA1509	KIAA1509	Hypothetical protein, Plasmid	150	4118
  AB040955	KIAA1522	KIAA1522 protein	Hypothetical protein	151	4119
  AB040960	FLJ22670	lymphocyte alpha-	Hypothetical protein, Kinase	152	4120
  		kinase
  AB040961	DTX2	deltex homolog 2	Nuclear protein, Repeat, Metal-	153	4121
  		(Drosophila)	binding, Zinc, Zinc-finger, Alternative
  			splicing, Polymorphism
  AB040968	HCN3	hyperpolarization	Transport, Ion transport, Ionic	154	4122
  		activated cyclic	channel, Voltage-gated channel,
  		nucleotide-gated	Potassium channel, Potassium,
  		potassium channel 3	Potassium transport, Sodium
  			transport, cAMP, cAMP-binding,
  			Transmembrane, Glycoprotein,
  			Sodium channel
  AB040969	KIAA1536	KIAA1536 protein	Hypothetical protein	155	4123
  AB040972	FLJ11560	Homo sapiens	Hypothetical protein	156	4124
  		mRNA for KIAA1539
  		protein, partial cds.
  AF000560		hypothetical protein	Metal-binding, Zinc, Zinc-finger	157	4125
  		LOC126208
  AF007217	TRIP11	thyroid hormone	Antigen, Golgi stack, Coiled coil,	158	4126
  		receptor interactor	Chromosomal translocation,
  		11	Hypothetical protein
  AF011757	S100A12	S100 calcium	Calcium-binding, Zinc, Metal-binding	159	4127
  		binding protein A12
  		(calgranulin C)
  AF016267	TNFRSF10C	tumor necrosis factor	Receptor, Apoptosis, Glycoprotein,	160	4128
  		receptor superfamily,	Repeat, GPI-anchor, Signal,
  		member 10c, decoy	Lipoprotein
  		without an
  		intracellular domain
  AF016495	AQP9	aquaporin 9	Transport, Repeat, Transmembrane	161	4129
  AF017433	ZNF213	zinc finger protein	Transcription regulation, DNA-	162	4130
  		213	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  AF026816	ITPA	inosine	Hydrolase, Nucleotide metabolism,	163	4131
  		triphosphatase	Disease mutation
  		(nucleoside
  		triphosphate
  		pyrophosphatase)
  AF031166	SRP46	Splicing factor,		164	4132
  		arginine/serine-rich,
  		46 kD
  AF034803	PPFIBP2	PTPRF interacting	Receptor, Hypothetical protein	165	4133
  		protein, binding
  		protein 2 (liprin beta
  		2)
  AF035307		plexin C1		166	4134
  AF038193		ADP-ribosylation	GTP-binding, Multigene family,	167	4135
  		factor-like 3	Polymorphism
  AF038535	SYT7	synaptotagmin VII	Transmembrane, Repeat, Synapse	168	4136
  AF038554	DENR	density-regulated	Hypothetical protein	169	4137
  		protein
  AF043469	NXPH4	serine	Transferase, Methyltransferase,	170	4138
  		hydroxymethyltransferase 2	Pyridoxal phosphate, One-carbon
  		(mitochondrial)	metabolism, Mitochondrion, Transit
  			peptide, Glycoprotein, Repeat,
  			Signal, Hypothetical protein
  AF045229	RGS10	regulator of G-	Signal transduction inhibitor,	171	4139
  		protein signalling 10	Lipoprotein, Palmitate, Alternative
  			splicing, Polymorphism
  AF049140	UBE2V2	ubiquitin-conjugating	Ligase, Ubl conjugation pathway,	172	4140
  		enzyme E2 variant 2	Vitamin D
  AF052093	NJMU-R1	protein kinase Njmu-		173	4141
  		R1
  AF052117		chloride channel 4	Ionic channel, Ion transport, Chloride	174	4142
  			channel, Chloride, Voltage-gated
  			channel, Transmembrane, CBS
  			domain, Repeat
  AF052159		protein tyrosine		175	4143
  		phosphatase-like
  		(proline instead of
  		catalytic arginine),
  		member b
  AF052167	MRS2L	MRS2-like,	Signal, Hypothetical protein	176	4144
  		magnesium
  		homeostasis factor
  		(S. cerevisiae)
  AF052169	LOC115207	potassium channel	Hypothetical protein	177	4145
  		tetramerisation
  		domain containing
  		12
  AF052181		epimorphin		178	4146
  AF055006	SEC6	SEC6-like 1 (S. cerevisiae)	Hypothetical protein, Exocytosis,	179	4147
  			Transport, Protein transport, Coiled
  			coil, Alternative splicing
  AF055012	TGIF2	TGFB-induced factor	DNA-binding, Homeobox,	180	4148
  		2 (TALE family	Transcription regulation, Nuclear
  		homeobox)	protein, Phosphorylation
  AF055016	C13orf1	chromosome 13	Hypothetical protein	181	4149
  		open reading frame 1
  AF055019		homeodomain	Transferase, Serine/threonine-	182	4150
  		interacting protein	protein kinase, ATP-binding, Nuclear
  		kinase 2	protein, Alternative splicing
  AF055029		hypothetical protein		183	4151
  		LOC151162
  AF055270	SFRS7	Homo sapiensheat-	Nuclear protein, RNA-binding,	184	4152
  		shock suppressed	mRNA splicing, Alternative splicing,
  		protein 1 (HSSG1)	Phosphorylation, Repeat, Zinc-
  		mRNA, complete	finger, Hypothetical protein
  		cds.
  AF059531	PRMT3	protein arginine N-	Hypothetical protein, Transferase,	185	4153
  		methyltransferase 3	Methyltransferase, Zinc-finger
  AF062341	CTNND1	catenin (cadherin-	Cytoskeleton, Structural protein,	186	4154
  		associated protein),	Phosphorylation, Repeat, Cell
  		delta 1	adhesion, Coiled coil, Nuclear
  			protein, Alternative splicing
  AF063020	PSIP2	PC4 and SFRS1	Receptor	187	4155
  		interacting protein 1
  AF067972	DNMT3A	DNA (cytosine-5-)-	Methyltransferase, Transferase,	188	4156
  		methyltransferase 3	Zinc-finger, Metal-binding, Nuclear
  		alpha	protein, Hypothetical protein
  AF068296	MRPS35	mitochondrial	Hypothetical protein, Ribosomal	189	4157
  		ribosomal protein	protein, Mitochondrion
  		S35
  AF070587		Clone 24741 mRNA		190	4158
  		sequence
  AF070643	LOC55977	intraflagellar		191	4159
  		transport protein
  		IFT20
  AF072810	BAZ1B	bromodomain	Transcription regulation,	192	4160
  		adjacent to zinc	Bromodomain, Zinc-finger, Coiled
  		finger domain, 1B	coil, Nuclear protein, Alternative
  			splicing, Williams-Beuren syndrome
  AF073519	SERF1A	small EDRK-rich	Alternative splicing	193	4161
  		factor 1A (telomeric)
  AF073931	CACNA1H	calcium channel,	Ionic channel, Transmembrane, Ion	194	4162
  		voltage-dependent,	transport, Voltage-gated channel,
  		alpha 1H subunit	Calcium channel, Glycoprotein,
  			Repeat, Multigene family, Calcium-
  			binding, Phosphorylation, Alternative
  			splicing
  AF077965	CLN3	ceroid-lipofuscinosis,	Transmembrane, Lysosome,	195	4163
  		neuronal 3, juvenile	Glycoprotein, Alternative splicing,
  		(Batten, Spielmeyer-	Neuronal ceroid lipofuscinosis,
  		Vogt disease)	Disease mutation
  AF078843	LOC51202	DEAD (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	196	4164
  		Asp) box polypeptide	Hypothetical protein
  		47
  AF085243	ZNF236	zinc finger protein	Metal-binding, Nuclear protein, Zinc,	197	4165
  		236	Zinc-finger, Hypothetical protein,
  			Transcription regulation, DNA-
  			binding, Repeat, Alternative splicing
  AF090935	C20orf3	Homo sapiensclone	Transmembrane, Signal-anchor,	198	4166
  		HQ0569.	Glycoprotein, Polymorphism
  AF097021	GW112	differentially		199	4167
  		expressed in
  		hematopoietic
  		lineages
  AF112213	C20orf24	chromosome	20	Alternative splicing	200	4168
  		open reading frame
  		24
  AF112219	ESD	esterase	Hydrolase, Serine esterase,	201	4169
  		D/formylglutathione	Polymorphism
  		hydrolase
  AF113694	NF2	neurofibromin	2	Structural protein, Cytoskeleton,	202	4170
  		(bilateral acoustic	Anti-oncogene, Disease mutation,
  		neuroma)	Alternative splicing, Deafness, 3D-
  			structure
  AF114264	nexilin	nexilin (F actin	Hypothetical protein	203	4171
  		binding protein)
  AF116238	PUS1	pseudouridylate	Lyase, tRNA processing, Nuclear	204	4172
  		synthase 1	protein
  AF117236	MATR3	matrin	3	Nuclear protein, RNA-binding,	205	4173
  			Repeat, Zinc-finger
  AF119665	PP	pyrophosphatase	Hydrolase, Metal-binding,	206	4174
  		(inorganic)	Magnesium
  AF119856	PRO1851	Homo sapiens	Acute phase, Serine protease	207	4175
  		mRNA for PK-120,	inhibitor, Repeat, Signal, Multigene
  		complete cds.	family, Glycoprotein, Alternative
  			splicing, Polymorphism
  AF121856	SNX6	sorting nexin	6	Hypothetical protein, Transport,	208	4176
  			Protein transport
  AF126749	SCA8	SCA8 mRNA, repeat		209	4177
  		region
  AF127765	CAPN3	calpain	3, (p94)	Hydrolase, Thiol protease, Calcium-	210	4178
  			binding, Multigene family, Repeat,
  			Disease mutation, Polymorphism,
  			Alternative splicing
  AF131760	LRP10	low density	Hypothetical protein, Plasmid	211	4179
  		lipoprotein receptor-
  		related protein 10
  AF131764	MPP5	membrane protein,	Hypothetical protein, SH3 domain,	212	4180
  		palmitoylated 5	Membrane
  		(MAGUK p55
  		subfamily member 5)
  AF131768	FLJ13657	chromosome 9 open	Hypothetical protein	213	4181
  		reading frame 82
  AF131774	FLJ14800	hypothetical protein	Hypothetical protein	214	4182
  		FLJ14800
  AF131775	MGC5560	hypothetical protein	Hypothetical protein	215	4183
  		MGC5560
  AF131784		RAB27B, member	GTP-binding, Lipoprotein,	216	4184
  		RAS oncogene	Prenylation
  		family
  AF131803	MGC5508	hypothetical protein	Hypothetical protein	217	4185
  		MGC5508
  AF131812		likely ortholog of	Hypothetical protein	218	4186
  		mouse monocyte
  		macrophage 19
  AF131838	FLJ12806	hypothetical protein	Hypothetical protein	219	4187
  		FLJ12806
  AF131842	KIAA1857	netrin G2	Hypothetical protein, EGF-like	220	4188
  			domain, Laminin EGF-like domain,
  			Neurogenesis, Glycoprotein, GPI-
  			anchor, Membrane, Signal, Repeat,
  			Lipoprotein
  AF131859	PA	sulfide quinone	Oxidoreductase, Flavoprotein, FAD,	221	4189
  		reductase-like	NADP, Mitochondrion, Transit
  		(yeast)	peptide, Polymorphism
  AF134404	FADS3	fatty acid desaturase 3	Heme	222	4190
  AF146277	CD2AP	CD2-associated	SH3 domain, SH3-binding,	223	4191
  		protein	Phosphorylation, Coiled coil, Repeat
  AF152338	PCDHGC4	protocadherin	Calcium, Calcium-binding, Cell	224	4192
  		gamma subfamily C, 3	adhesion, Glycoprotein,
  			Transmembrane, Alternative
  			splicing, Repeat, Signal, Multigene
  			family
  AF152339	PCDHGC5	protocadherin	Calcium, Calcium-binding, Cell	225	4193
  		gamma subfamily C, 3	adhesion, Glycoprotein,
  			Transmembrane, Alternative
  			splicing, Repeat, Signal, Multigene
  			family
  AF155107	FLJ11806	nuclear protein	Plasmid, Hypothetical protein	226	4194
  		UKp68
  AF156603	WBSCR14	Williams Beuren	Transcription regulation, Repressor,	227	4195
  		syndrome	Nuclear protein, DNA-binding,
  		chromosome region	Williams-Beuren syndrome,
  		14	Alternative splicing
  AF161339	ARHGAP9	Rho GTPase	Hypothetical protein,SH3 domain	228	4196
  		activatingprotein 9
  AF161417	DKFZp564D177	nipsnap homolog 3A	Hypothetical protein	229	4197
  		(C. elegans)
  AF161442	HSPC324	Similar to HSPC324		230	4198
  		(LOC389811),
  		mRNA
  AF167706	CRIM1	cysteine-rich motor	Signal	231	4199
  		neuron 1
  AF187859	HSPBP1	hsp70-interacting	Hypothetical protein	232	4200
  		protein
  AF202063	FGFR4	fibroblast growth	ATP-binding, Immunoglobulin	233	4201
  		factor receptor 4	domain, Kinase, Receptor,
  			Transferase, Tyrosine-protein
  			kinase, Glycoprotein,
  			Phosphorylation, Transmembrane,
  			Repeat, Signal, Polymorphism, 3D-
  			structure
  AF209931	7h3	hypothetical protein	Hypothetical protein	234	4202
  		FLJ13511
  AF212842	LILRA3	leukocyte Ig-like	Receptor, Repeat, Signal, Immune	235	4203
  		receptor 9	response, Immunoglobulin domain,
  			Glycoprotein, Antigen, Multigene
  			family, Polymorphism
  AF217798	NDEL1	nudE nuclear	Hypothetical protein	236	4204
  		distribution gene E
  		homolog like 1 (A. nidulans)
  AF220417	LGTN	ligatin	Membrane, Alternative splicing	237	4205
  AF222694	LGALS12	lectin, galactoside-	Galectin, Lectin, Repeat, Nuclear	238	4206
  		binding, soluble, 12	protein, Alternative splicing
  		(galectin 12)
  AF227924	SIGLEC9	sialic acid binding Ig-	Cell adhesion, Lectin, Antigen,	239	4207
  		likelectin 9	Transmembrane, Signal,
  			Glycoprotein, Immunoglobulin
  			domain, Repeat, Polymorphism
  AF228704	GSR	glutathione	FAD, Flavoprotein, Oxidoreductase,	240	4208
  		reductase	Redox-active center, NADP,
  			Acetylation, Alternative initiation,
  			Mitochondrion, Transit peptide, 3D-
  			structure, Polymorphism
  AF232216	PIH1	Homo sapiens		241	4209
  		pregnancy-induced
  		hypertension
  		syndrome-related
  		protein (PIH1)
  		mRNA, partial cds.
  AF237413	RAP1GDS1	RAP1, GTP-GDP	GTPase activation, Repeat,	242	4210
  		dissociation	Alternative splicing
  		stimulator
  1
  AF241831	HABP4	hyaluronan binding	Hypothetical protein	243	4211
  		protein 4
  AF242771		Mesenchymal stem		244	4212
  		cell protein DSC96
  		mRNA, partial cds
  AF244088	ZNF16	zinc finger protein 16	Hypothetical protein, Metal-binding,	245	4213
  		(KOX 9)	Nuclear protein, Zinc, Zinc-finger,
  			Transcription regulation, DNA-
  			binding, Repeat
  AF246221	ITM2B	integral membrane	Hypothetical protein,	246	4214
  		protein 2B	Transmembrane, Signal-anchor,
  			Disease mutation, Amyloid,
  			Deafness
  AF257175	PECI	peroxisomal D3,D2-	Isomerase, Peroxisome,	247	4215
  		enoyl-CoA	Hypothetical protein
  		isomerase
  AF260261	ABI-2	abl interactor 2	Kinase, SH3 domain	248	4216
  AF272357	NPDC1	neural proliferation,	Signal, Transmembrane,	249	4217
  		differentiation and	Hypothetical protein
  		control, 1
  AI076473_RC		rap2 interacting	Hypothetical protein	250	4218
  		protein x
  AI282511_RC	PTRF	hypothetical protein	Hypothetical protein	251	4219
  		FLJ10534
  AI286310_RC	HSPA5	qu91g07.x1	ATP-binding, Endoplasmic reticulum,	252	4220
  		NCI_CGAP_Gas4	Signal
  		Homo sapienscDNA
  		clone
  		IMAGE: 1979484 3′
  		similar to
  		gb: M19645_cds1 78 KD
  		GLUCOSE
  		REGULATED
  		PROTEIN
  		PRECURSOR
  		(HUMAN); mRNA
  		sequence.
  AI339981_RC		hypothetical protein		253	4221
  		LOC153346
  AI347139_RC		hypothetical protein		254	4222
  		MGC39372
  AI355990_RC		qy51g12.x1		255	4223
  		NCI_CGAP_Brn23
  		Homo sapienscDNA
  		clone
  		IMAGE: 2015590 3′,
  		mRNA sequence.
  AI434777_RC		CDNA FLJ44280 fis,		256	4224
  		clone
  		TRACH2001684
  AI493593_RC		th39c02.x1		257	4225
  		NCI_CGAP_Pan1
  		Homo sapienscDNA
  		clone
  		IMAGE: 2120642 3′,
  		mRNA sequence.
  AI668686_RC	FLJ38281	hypothetical protein	Hypothetical protein, Metal-binding,	258	4226
  		FLJ38281	Zinc, Zinc-finger
  AI677876_RC		CDNA clone		259	4227
  		IMAGE: 4648334,
  		partial cds
  AI695056_RC		Sarcoma antigen		260	4228
  		NY-SAR-79 mRNA,
  		partial cds
  AI928427_RC		Transcribed		261	4229
  		sequences
  AJ000480	C8FW	phosphoprotein	ATP-binding, Receptor, Transferase	262	4230
  		regulated by
  		mitogenic pathways
  AJ010228	RFPL1	ret finger protein-like 1	Zinc-finger, Metal-binding	263	4231
  AJ010842	NTPBP	XPA binding protein 1	GTP-binding	264	4232
  AJ011414	plexin-	plexin B1	Hypothetical protein, Receptor,	265	4233
  	B1/SEP		Signal
  AJ133115	THG-1	TSC-22-like	Hypothetical protein, Transcription	266	4234
  			regulation, Repressor, Nuclear
  			protein
  AJ225028	GABBR1	gamma-aminobutyric	Hypothetical protein, G-protein	267	4235
  		acid (GABA) B	coupled receptor, Postsynaptic
  		receptor, 1	membrane, Repeat, Signal,
  			Transmembrane, Coiled coil, Sushi,
  			Glycoprotein, Alternative splicing,
  			Polymorphism, Receptor
  AJ243107	APAF1	Homo sapiens	Apoptosis, ATP-binding, Repeat,	268	4236
  		mRNA for apoptotic	WD repeat, Alternative splicing, 3D-
  		protease activating	structure
  		factor-1 (Apaf-1
  		gene) (short form).
  AJ249377	IGHM	immunoglobulin	Immunoglobulin domain,	269	4237
  		lambda joining 3	Immunoglobulin C region,
  			Glycoprotein, Repeat, Pyrrolidone
  			carboxylic acid, Polymorphism,
  			Membrane, Hypothetical protein,
  			Receptor, T-cell, Signal
  AJ270996	TRPM5	transient receptor	Ionic channel, Transmembrane	270	4238
  		potential cation
  		channel, subfamily
  		M,member 5
  AJ271684	CLECSF5	C-type (calcium	Transmembrane, Lectin	271	4239
  		dependent,
  		carbohydrate-
  		recognition domain)
  		lectin,superfamily
  		member
  5
  AJ272057	STRAIT11499	MID1 interacting	Hypothetical protein	272	4240
  		G12-like protein
  AK000001	FLJ00001	chromosome 9 open	Hypothetical protein	273	4241
  		reading frame 28
  AK000004	FGD3	FGD1 family,		274	4242
  		member 3
  AK000007	FLJ00007	hypothetical protein	SH3 domain	275	4243
  		FLJ00007
  AK000014	HYPE	Huntingtin	Hypothetical protein	276	4244
  		interacting protein E
  AK000035	FLJ22390	hypothetical protein	Hypothetical protein	277	4245
  		FLJ22390
  AK000168	KIAA1919	Homo sapienscDNA	Hypothetical protein	278	4246
  		FLJ20161 fis, clone
  		COL09252, highly
  		similar to L33930
  		Homo sapiensCD24
  		signal transducer
  		mRNA.
  AK000175		hypothetical protein		279	4247
  		LOC93444
  AK000212	FLJ10140	tRNA (5-	Hypothetical protein, Transferase,	280	4248
  		methylaminomethyl-	Methyltransferase, tRNA processing
  		2-thiouridylate)-
  		methyltransferase 1
  AK000216	FLJ20209	hypothetical protein		281	4249
  		FLJ20209
  AK000242	RALGDS	ral guanine	Guanine-nucleotide releasing factor,	282	4250
  		nucleotide	3D-structure, Hypothetical protein
  		dissociation
  		stimulator
  AK000260	CDK5RAP3	Homo sapienscDNA		283	4251
  		FLJ20253 fis, clone
  		COLF6895.
  AK000354	KIAA1892	KIAA1892	Hypothetical protein, Repeat, WD	284	4252
  			repeat
  AK000425	FLJ25555	hypothetical protein	Hypothetical protein	285	4253
  		FLJ25555
  AK000435	LOC90987	zinc finger protein	Hypothetical protein, Metal-binding,	286	4254
  		251	Nuclear protein, Zinc, Zinc-finger
  AK000539	DKFZP564K0822	hypothetical protein	Hypothetical protein	287	4255
  		DKFZp564K0822
  AK000552	WDR5	WD repeat domain 5	Hypothetical protein, WD repeat,	288	4256
  			Repeat
  AK000617	NFRKB	hypothetical protein	Hypothetical protein, Ligase, Ubl	289	4257
  		LOC92912	conjugation pathway
  AK000660		cyclin-dependent		290	4258
  		kinase 6
  AK000684	FLJ22104	hypothetical protein	Hypothetical protein	291	4259
  		FLJ22104
  AK000689	CLONE24945	arrestin domain	Hypothetical protein	292	4260
  		containing 2
  AK000703	FLJ20696	hypothetical protein	Hypothetical protein	293	4261
  		FLJ20696
  AK000729		solute carrier family	Hypothetical protein	294	4262
  		36 (proton/amino
  		acid symporter),
  		member 1
  AK000757	BCL2L1	sortilin 1	Apoptosis, Mitochondrion,	295	4263
  			Alternative splicing,
  			Transmembrane, 3D-structure
  AK000787		CDNA FLJ20780 fis,		296	4264
  		clone COL04256
  AK000803		hypothetical protein		297	4265
  		LOC90624
  AK000808	MGC4796	Ser/Thr-like kinase	Hypothetical protein, ATP-binding,	298	4266
  			Kinase, Serine/threonine-protein
  			kinase, Transferase
  AK000822	DKFZP564M182	DKFZP564M182	Hypothetical protein	299	4267
  		protein
  AK000824	TCTA	T-cell leukemia		300	4268
  		translocation altered
  		gene
  AK000838	KIAA1295	KIAA1295 protein	Hypothetical protein	301	4269
  AK000933		opsin 3	Photoreceptor, Retinal protein,	302	4270
  		(encephalopsin,	Transmembrane, Lipoprotein,
  		panopsin)	Palmitate, G-protein coupled
  			receptor, GTPase activation
  AK000939		hypothetical protein		303	4271
  		LOC286272
  AK000967	3PAP	phosphatidylinositol-	Hypothetical protein	304	4272
  		3-phosphate
  		associated protein
  AK001022	ISL2	ISL2 transcription	Homeobox, DNA-binding,	305	4273
  		factor,	Developmental protein, Nuclear
  		LIM/homeodomain,	protein, Repeat, LIM domain, Metal-
  		(islet-2)	binding, Zinc, Multigene family
  AK001036		MAD, mothers	Transcription regulation, Multigene	306	4274
  		against	family, Phosphorylation
  		decapentaplegic
  		homolog 5
  		(Drosophila)
  AK001069	UPF3A	CDNA FLJ10207 fis,		307	4275
  		clone
  		HEMBA1005475
  AK001163	PAICS	phosphoribosylaminoimidazole	Multifunctional enzyme, Purine	308	4276
  		carboxylase,	biosynthesis, Ligase, Lyase,
  		phosphoribosylaminoimidazole	Decarboxylase
  		succinocarboxamide
  		synthetase
  AK001166	FLJ11252	HBxAg	Hypothetical protein	309	4277
  		transactivated
  		protein 1
  AK001228		chromosome 6 open		310	4278
  		reading frame 107
  AK001319	C8FW	phosphoprotein	ATP-binding, Receptor, Transferase	311	4279
  		regulated by
  		mitogenic pathways
  AK001362	ESDN	endothelial and	Hypothetical protein	312	4280
  		smooth muscle cell-
  		derived neuropilin-
  		like protein
  AK001394		hypothetical protein		313	4281
  		DKFZp762K222
  AK001452	FLJ10839	Homo sapienscDNA	Hypothetical protein	314	4282
  		FLJ10590 fis, clone
  		NT2RP2004392,
  		weakly similar to
  		MNN4 PROTEIN.
  AK001469	GNPNAT1	glucosamine-	Hypothetical protein, Transferase	315	4283
  		phosphate N-
  		acetyltransferase 1
  AK001478	ARHU	ras homolog gene	GTP-binding, Lipoprotein,	316	4284
  		family, member U	Prenylation
  AK001492	FLJ10637	hypothetical protein	Hypothetical protein	317	4285
  		FLJ10637
  AK001499	FLJ10637	hypothetical protein	Hypothetical protein	318	4286
  		FLJ10637
  AK001503		CDNA FLJ10641 fis,	Metal-binding, Zinc, Zinc-finger	319	4287
  		clone
  		NT2RP2005748
  AK001526	DKFZp667B1218	hypothetical protein	Hypothetical protein	320	4288
  		DKFZp667B1218
  AK001536		Human full-length	Plasmid	321	4289
  		cDNA 5-PRIME end
  		of clone
  		CS0DK007YB08 of
  		HeLa cells ofHomo
  		sapiens(human)
  AK001539	TEM6	tensin-like SH2	Hypothetical protein	322	4290
  		domain containing 1
  AK001565	AP3M1	adaptor-related	Golgi stack, Protein transport,	323	4291
  		protein complex 3,	Transport, Hypothetical protein
  		mu 1 subunit
  AK001579	ARAP3	ARF-GAP, RHO-	Hypothetical protein	324	4292
  		GAP, ankyrin repeat
  		and plekstrin
  		homology domains-
  		containing protein 3
  AK001612		hypothetical protein		325	4293
  		LOC90784
  AK001630	ETS1	v-ets	Proto-oncogene, Nuclear protein,	326	4294
  		erythroblastosis	Transcription regulation, DNA-
  		virus E26 oncogene	binding, Phosphorylation, Alternative
  		homolog 1 (avian)	splicing, 3D-structure
  AK001731	MGC17943	hypothetical protein	Hypothetical protein	327	4295
  		MGC17943
  AK001758	THOC2	THO complex 2	Transport, mRNA transport, mRNA	328	4296
  			processing, mRNA splicing, Nuclear
  			protein, RNA-binding, Alternative
  			splicing
  AK001822		chromosome 9 open	Hypothetical protein	329	4297
  		reading frame 37
  AK001913	CL25084	XTP3-transactivated	Hypothetical protein	330	4298
  		protein B
  AK001980	ADPRTL2	ADP-	Transferase, Glycosyltransferase,	331	4299
  		ribosyltransferase	NAD, DNA-binding, Nuclear protein,
  		(NAD+; poly(ADP-	Alternative splicing
  		ribose) polymerase)-
  		like 2
  AK002039	MRVI1	murine retrovirus		332	4300
  		integration site 1
  		homolog
  AK002081	FLJ10287	hypothetical protein	Hypothetical protein	333	4301
  		FLJ10287
  AK002141	PIK4CA	Homo sapienscDNA	Transferase, Kinase	334	4302
  		FLJ11279 fis, clone
  		PLACE1009444,
  		highly similar to
  		PHOSPHATIDYLINOSITOL
  		4-KINASE
  		ALPHA (EC
  		2.7.1.67).
  AK002146		hypothetical protein		335	4303
  		LOC153684
  AK002174	KLHL5	kelch-like 5	Cytoskeleton, Actin-binding, Repeat,	336	4304
  		(Drosophila)	Kelch repeat, Alternative splicing
  AL049232		Homo sapiens		337	4305
  		mRNA; cDNA
  		DKFZp564P1816
  		(from clone
  		DKFZp564P1816).
  AL049266		Homo sapiens		338	4306
  		mRNA; cDNA
  		DKFZp564F093
  		(from clone
  		DKFZp564F093).
  AL049279		MRNA; cDNA		339	4307
  		DKFZp564I083
  		(from clone
  		DKFZp564I083)
  AL049299	DJ465N24.2.1	hypothetical protein	Hypothetical protein	340	4308
  		dJ465N24.2.1
  AL049309	SFRS12	splicing factor,	Nuclear protein, mRNA processing,	341	4309
  		arginine/serine-rich	mRNA splicing, Spliceosome,
  		12	Alternative splicing
  AL049365	FTL	hypothetical protein	Acetylation, Iron storage, Multigene	342	4310
  		MGC50853	family
  AL049381		pre-B-cell leukemia	Transcription regulation, DNA-	343	4311
  		transcription factor 1	binding, Nuclear protein, Activator,
  			Repressor, Homeobox, Proto-
  			oncogene, Chromosomal
  			translocation, Alternative splicing,
  			Steroidogenesis, Sexual
  			differentiation, 3D-structure
  AL049397		CGI-146 protein	Hypothetical protein	344	4312
  AL049415	ADAM19	a disintegrin and	Hydrolase, Metalloprotease, Zinc,	345	4313
  		metalloproteinase	Signal, Glycoprotein, Zymogen,
  		domain 19 (meltrin	Transmembrane, EGF-like domain,
  		beta)	SH3-binding, Alternative splicing,
  			Hypothetical protein
  AL049431	FLJ20619	hypothetical protein	Hypothetical protein	346	4314
  		FLJ20619
  AL049450		hypothetical protein		347	4315
  		LOC339287
  AL049471		AT rich interactive	Hypothetical protein	348	4316
  		domain 5B (MRF1-
  		like)
  AL049962		hypothetical protein		349	4317
  		LOC286148
  AL049963	LOC64116	solute carrier family	Hypothetical protein	350	4318
  		39 (zinc transporter),
  		member 8
  AL050002		hypothetical protein	Hypothetical protein	351	4319
  		LOC169611
  AL050021		solute carrier family	Hypothetical protein,	352	4320
  		7 (cationic amino	Transmembrane, Glycoprotein,
  		acid transporter, y+	Transport, Amino-acid transport,
  		system),member 1	Receptor
  AL050022	DKFZP564D116	DKFZP564D116	Hypothetical protein	353	4321
  		protein
  AL050050	TULIP1	GTPase activating	Hypothetical protein	354	4322
  		RANGAP domain-
  		like 2 pseudogene
  AL050060	DKFZP566H073	DKFZP566H073	Hypothetical protein, Metal-binding,	355	4323
  		protein	Zinc, Zinc-finger
  AL050091	GRINL1A	glutamate receptor,	Hypothetical protein, Receptor	356	4324
  		ionotropic, N-methyl
  		D-aspartate-like 1A
  AL050126	LAP1B	lamina-associated	Hypothetical protein	357	4325
  		polypeptide 1B
  AL050148		sortingnexin 1	Transport, Protein transport, Golgi	358	4326
  			stack, Alternative splicing
  AL050163	PIK3AP	hematopoietic cell	Hypothetical protein,	359	4327
  		signal transducer	Transmembrane
  AL050164	CDYL	chromodomain	Hypothetical protein, Nuclear protein	360	4328
  		protein, Y-like
  AL050170	SLC26A6	solute carrier family	Hypothetical protein,	361	4329
  		26,member 6	Transmembrane, Alternative
  			splicing, Polymorphism
  AL050173	C21orf25	chromosome 21	Hypothetical protein	362	4330
  		open reading frame
  		25
  AL050217	BRD2	dehydrogenase/reductase	Oxidoreductase	363	4331
  		(SDR family)
  		member 1
  AL050346	C22orf3	chromosome 22	Hypothetical protein	364	4332
  		open reading frame 3
  AL079294		MRNA full length	Hypothetical protein	365	4333
  		insert cDNA clone
  		EUROIMAGE
  		362780
  AL079298	MCCC2	methylcrotonoyl-	Mitochondrion, Transit peptide,	366	4334
  		Coenzyme A	Ligase, Disease mutation,
  		carboxylase 2 (beta)	Alternative splicing
  AL080110		progestin and	Hypothetical protein	367	4335
  		adipoQ receptor
  		family member III
  AL080114		chromosome 10	Hypothetical protein	368	4336
  		open reading frame
  		72
  AL080125	ZNF20	zinc finger protein 20	Hypothetical protein, Metal-binding,	369	4337
  		(KOX 13)	Nuclear protein, Zinc, Zinc-finger,
  			Transcription regulation, DNA-
  			binding, Repeat
  AL080156	DKFZP434J214	TCDD-inducible	Hypothetical protein	370	4338
  		poly(ADP-ribose)
  		polymerase
  AL080169	DKFZP434C171	DKFZP434C171	Hypothetical protein	371	4339
  		protein
  AL080182		N-deacetylase/N-	Hypothetical protein, Transferase,	372	4340
  		sulfotransferase	Transmembrane, Glycoprotein, Golgi
  		(heparan	stack, Signal-anchor
  		glucosaminyl) 2
  AL080192		hypothetical protein	Hypothetical protein	373	4341
  		LOC253782
  AL096745	TBCD	tubulin-specific	Hypothetical protein	374	4342
  		chaperone d
  AL109669	IL16	interleukin 16	Cytokine, Chemotaxis, Repeat, 3D-	375	4343
  		(lymphocyte	structure
  		chemoattractant
  		factor)
  AL109693	FLJ12587	hypothetical protein	Hypothetical protein	376	4344
  		FLJ12587
  AL109695		solute carrier organic	Transmembrane, Transport, Ion	377	4345
  		anion transporter	transport, Glycoprotein
  		family, member 3A1
  AL109699		MRNA full length	Hypothetical protein	378	4346
  		insert cDNA clone
  		EUROIMAGE
  		375854
  AL109705		MRNA full length		379	4347
  		insert cDNA clone
  		EUROIMAGE 73337
  AL109786	WDR9	chromosome 21	Bromodomain, Repeat, WD repeat	380	4348
  		open reading frame
  		107
  AL109817	FTCD	formiminotransferase	Hypothetical protein, Transferase,	381	4349
  		cyclodeaminase	Lyase, Histidine metabolism,
  			Multifunctional enzyme, Pyridoxal
  			phosphate, Folate-binding,
  			Alternative splicing, Disease
  			mutation, Polymorphism
  AL110152		CD109 antigen (Gov	Hypothetical protein	382	4350
  		platelet alloantigens)
  AL110188	ZNF10	zinc finger protein 10	Hypothetical protein, Metal-binding,	383	4351
  		(KOX 1)	Nuclear protein, Zinc, Zinc-finger,
  			Transcription regulation, DNA-
  			binding, Repeat
  AL110200		Homo sapiens		384	4352
  		mRNA; cDNA
  		DKFZp586B0922
  		(from clone
  		DKFZp586B0922).
  AL110202	PORIMIN	pro-oncosis receptor	Hypothetical protein, Receptor,	385	4353
  		inducing membrane	Transmembrane
  		injury gene
  AL110210	PTPN23	protein tyrosine	Hydrolase, Hypothetical protein,	386	4354
  		phosphatase, non-	Receptor
  		receptor type
  23
  AL110218	SLB	selective LIM binding	Hypothetical protein	387	4355
  		factor, rat homolog
  AL110238	RRN3	RNA polymerase I	Initiation factor, Hypothetical protein	388	4356
  		transcription factor
  		RRN3
  AL110262	NCBP2	nuclear cap binding	Transport, mRNA transport, Nuclear	389	4357
  		protein subunit 2,	protein, RNA-binding, 3D-structure
  		20 kDa
  AL110277	KIAA0916	protein associated	Hypothetical protein	390	4358
  		with Myc
  AL117415	ADAM33	Homo sapiens	Hypothetical protein, Hydrolase,	391	4359
  		mRNA; cDNA	Metalloprotease, Zinc, Signal,
  		DKFZp434K0521	Glycoprotein, Zymogen,
  		(from clone	Transmembrane, EGF-like domain,
  		DKFZp434K0521).	Alternative splicing, Integrin,
  			Protease
  AL117435	DKFZP434I216	DKFZP434I216	Hypothetical protein	392	4360
  		protein
  AL117448	RAB6IP1	RAB6 interacting	Hypothetical protein	393	4361
  		protein 1
  AL117452	FTHFSDC1	formyltetrahydrofolate	Hypothetical protein	394	4362
  		synthetase domain
  		containing 1
  AL117457	CFL2	cofilin 2 (muscle)	Nuclear protein, Actin-binding,	395	4363
  			Cytoskeleton, Phosphorylation,
  			Alternative splicing
  AL117458	IHPK2	inositol	Hypothetical protein, Kinase	396	4364
  		hexaphosphate
  		kinase
  2
  AL117462	ZFP385	zinc finger protein	Metal-binding, Zinc, Zinc-finger,	397	4365
  		385	Hypothetical protein
  AL117478	AGS3	G-protein signalling	Hypothetical protein	398	4366
  		modulator 1 (AGS3-
  		like,C. elegans)
  AL117519		hypothetical protein	Hypothetical protein, Metal-binding,	399	4367
  		LOC152485	Zinc, Zinc-finger
  AL117573	DKFZP434F2021	DKFZP434F2021	Hypothetical protein	400	4368
  		protein
  AL117578	DKFZP434C128	chromosome 21	Hypothetical protein	401	4369
  		open reading frame
  		30
  AL117609	DKFZp564O0463	DKFZP564O0463	Hypothetical protein, Repeat, WD	402	4370
  		protein	repeat
  AL117639	FLJ12890	CCR4-NOT	Hypothetical protein	403	4371
  		transcription
  		complex,subunit 10
  AL117643		activin A receptor,	Receptor, Transferase,	404	4372
  		type IB	Serine/threonine-protein kinase,
  			ATP-binding, Transmembrane,
  			Glycoprotein, Signal, Alternative
  			splicing, Phosphorylation,
  			Polymorphism
  AL117645	EG1	endothelial-derived	Hypothetical protein	405	4373
  		gene 1
  AL117654	ARH	LDL receptor	Hypothetical protein	406	4374
  		adaptor protein
  AL122053	TRIM3	tripartite motif-	Zinc-finger, Coiled coil, Alternative	407	4375
  		containing 3	splicing
  AL122091	LOC56965	hypothetical protein	Hypothetical protein	408	4376
  		from EUROIMAGE
  		1977056
  AL122097	FLJ12519	hypothetical protein	Hypothetical protein, Repeat, WD	409	4377
  		FLJ12519	repeat
  AL122098	NICAL	NEDD9 interacting	Hypothetical protein, LIM domain,	410	4378
  		protein with calponin	Metal-binding, Zinc, Cytoskeleton
  		homology and LIM
  		domains
  AL122123		MRNA; cDNA		411	4379
  		DKFZp434M038
  		(from clone
  		DKFZp434M038)
  AL133021	STAB2	stabilin 2	EGF-like domain, Laminin EGF-like	412	4380
  			domain, Hypothetical protein,
  			Receptor
  AL133071	DKFZp434I1117	hypothetical protein	Hypothetical protein	413	4381
  		DKFZp434I1117
  AL133092	DKFZp434I0428	dispatched homolog	Hypothetical protein	414	4382
  		1 (Drosophila)
  AL133094	PHF10	PHD finger protein	Hypothetical protein	415	4383
  		10
  AL133115		cytosolic ovarian	Biological rhythms, Electron	416	4384
  		carcinoma antigen 1	transport, Growth regulation,
  			Oxidoreductase, NAD, Membrane,
  			Copper, Glycoprotein
  AL133116	FKBP10	Homo sapiens	Isomerase, Rotamase, Endoplasmic	417	4385
  		mRNA; cDNA	reticulum, Calcium-binding,
  		DKFZp586I0821	Glycoprotein, Phosphorylation,
  		(from clone	Repeat, Signal, Hypothetical protein
  		DKFZp586I0821).
  AL133117		THOcomplex 2	Transport, mRNA transport, mRNA	418	4386
  			processing, mRNA splicing, Nuclear
  			protein, RNA-binding, Alternative
  			splicing
  AL133426	AKAP13	A kinase (PRKA)	Kinase, Receptor, cAMP,	419	4387
  		anchor protein 13	Hypothetical protein
  AL133572	DKFZp434I0535	Homo sapiens	Hypothetical protein	420	4388
  		mRNA; cDNA
  		DKFZp434I0535
  		(from clone
  		DKFZp434I0535);
  		partial cds.
  AL133577		MRNA; cDNA		421	4389
  		DKFZp434G0972
  		(from clone
  		DKFZp434G0972)
  AL133580	SCOC	short coiled-coil	Hypothetical protein	422	4390
  		protein
  AL133581	FLJ25785	solute carrier family	Hypothetical protein	423	4391
  		39 (zinc transporter),
  		member 13
  AL133592	MGC15548	zinc finger protein	Hypothetical protein, Metal-binding,	424	4392
  		496	Zinc, Zinc-finger
  AL133622	KIAA0876	jumonji domain	Hypothetical protein	425	4393
  		containing 2B
  AL133632	DKFZp434E1818	Similar to	Hypothetical protein, Metal-binding,	426	4394
  		hypothetical protein	Zinc, Zinc-finger
  		(LOC389822),
  		mRNA
  AL133645		hypothetical protein		427	4395
  		LOC90133
  AL133662	KIAA0913	KIAA0913 protein	Hypothetical protein	428	4396
  AL136549	CYFIP2	cytoplasmic FMR1	Hypothetical protein	429	4397
  		interactingprotein 2
  AL137273	DKFZP434I0714	hypothetical protein	Hypothetical protein	430	4398
  		DKFZP434I0714
  AL137298	DNAJB6	MRNA; cDNA	Chaperone, Alternative splicing	431	4399
  		DKFZp434N2116
  		(from clone
  		DKFZp434N2116)
  AL137302	TEX27	testis expressed	Hypothetical protein	432	4400
  		sequence 27
  AL137397	FLJ21820	hypothetical protein	Hypothetical protein	433	4401
  		FLJ21820
  AL137421	RBM10	RNA binding motif	Hypothetical protein, Metal-binding,	434	4402
  		protein 10	Zinc, Zinc-finger, RNA-binding,
  			Nuclear protein, Repeat
  AL137423	GU2	DEAD (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	435	4403
  		Asp) box polypeptide	Hypothetical protein
  		50
  AL137431	WBSCR17	Williams-Beuren	Transferase, Hypothetical protein	436	4404
  		syndrome
  		chromosome region
  		17
  AL137442	C20orf177	chromosome 20	Hypothetical protein	437	4405
  		open reading frame
  		177
  AL137473	C20orf67	Homo sapiens	Alternative splicing, Hypothetical	438	4406
  		mRNA; cDNA	protein
  		DKFZp434E1723
  		(from clone
  		DKFZp434E1723);
  		partial cds.
  AL137477	CDH24	cadherin-like 24	Hypothetical protein, Calcium,	439	4407
  			Calcium-binding, Cell adhesion,
  			Glycoprotein, Transmembrane,
  			Repeat, Signal, Multigene family,
  			Alternative splicing, Plasmid
  AL137480	FNBP4	formin binding	Hypothetical protein	440	4408
  		protein 4
  AL137491		hypothetical protein		441	4409
  		LOC148696
  AL137509	DKFZp761A052	hypothetical protein	Hypothetical protein	442	4410
  		DKFZp761A052
  AL137514	IHPK2	inositol	Hypothetical protein, Kinase	443	4411
  		hexaphosphate
  		kinase 2
  AL137516	FLJ22059	zinc finger protein	Hypothetical protein, Metal-binding,	444	4412
  		574	Zinc, Zinc-finger, Nuclear protein
  AL137557	KIAA1529	KIAA1529	Hypothetical protein	445	4413
  AL137567	KIAA1238	KIAA1238 protein	Hypothetical protein	446	4414
  AL137579	SNX26	sorting nexin 26	Hypothetical protein, Transport,	447	4415
  			Protein transport
  AL137597	C20orf110	chromosome 20		448	4416
  		open reading frame
  		110
  AL137615	MKNK2	MAP kinase-	Hypothetical protein, ATP-binding,	449	4417
  		interacting	Kinase, Serine/threonine-protein
  		serine/threonine	kinase, Transferase,Translation
  		kinase
  2	regulation, Phosphorylation,
  			Alternative splicing
  AL137631	FBXW5	Homo sapiens	Hypothetical protein, Repeat, WD	450	4418
  		mRNA; cDNA	repeat
  		DKFZp434B205
  		(from clone
  		DKFZp434B205);
  		partial cds.
  AL137639	KIAA0721	TSPY-like 4	Hypothetical protein	451	4419
  AL137648	DKFZP434J1813	ER-resident protein	Redox-active center, Hypothetical	452	4420
  		ERdj5	protein
  AL137655		Homo sapiens	Hypothetical protein	453	4421
  		mRNA; cDNA
  		DKFZp434B2016
  		(from clone
  		DKFZp434B2016).
  AL137662	DKFZp434P086	hypothetical protein	Hypothetical protein, ATP-binding,	454	4422
  		LOC340371	Transferase
  AL137663	FLJ21791	pleckstrin homology-	Hypothetical protein	455	4423
  		like domain, family
  		B,member 2
  AL137665	TUBGCP6	tubulin, gamma	Microtubule, Repeat, Alternative	456	4424
  		complex associated	splicing
  		protein
  6
  AL137667	MAPK8	Homo sapiens	Transferase, Serine/threonine-	457	4425
  		mRNA; cDNA	protein kinase, ATP-binding,
  		DKFZp434B231	Phosphorylation, Alternative splicing
  		(from clone
  		DKFZp434B231).
  AL137707	LOC55901	TPTE and PTEN	Signal	458	4426
  		homologous inositol
  		lipid phosphatase
  		pseudogene
  AL137727	C14orf9	chromosome 14	Hypothetical protein,	459	4427
  		open reading frame 9	Transmembrane, Alternative splicing
  AL137733		hypothetical protein	Hypothetical protein	460	4428
  		LOC284701
  AL137736		Rho guanine	Hypothetical protein	461	4429
  		nucleotide exchange
  		factor (GEF) 19
  AL137764	LOC64744	hypothetical protein	Hypothetical protein	462	4430
  		AL133206
  AL157432	TERA	chromosome 12	Hypothetical protein	463	4431
  		open reading frame
  		14
  AL157449	LOC84687	protein phosphatase	Hypothetical protein	464	4432
  		1, regulatory subunit
  		9B, spinophilin
  AL157454	FLJ21313	HCV NS3-	Hypothetical protein	465	4433
  		transactivated
  		protein 2
  AL157455		Clone		466	4434
  		IMAGE: 5288750,
  		mRNA
  AL157457	PP1628	PH domain-	Hypothetical protein	467	4435
  		containing protein
  AL157465	FLJ20186	hypothetical protein	Hypothetical protein	468	4436
  		FLJ20186
  AL157480	SH3BP1	lectin, galactoside-	GTPase activation, SH3-binding,	469	4437
  		binding, soluble, 1	Hypothetical protein, Galectin,
  		(galectin 1)	Lectin, Multigene family, Acetylation
  AL157484		MRNA; cDNA		470	4438
  		DKFZp762M127
  		(from clone
  		DKFZp762M127)
  AL161960	FLJ21324	chromosome 21	Hypothetical protein	471	4439
  		open reading frame
  		97
  AL161972	ICAM2	hypothetical protein	3D-structure, Cell	472	4440
  		FLJ11724	adhesion, Glycoprotein, Immunoglobulin
  			domain, Repeat, Signal, Transmembrane
  AL161977	PCTK3	PCTAIRE protein	Hypothetical protein, ATP-binding,	473	4441
  		kinase 3	Kinase, Serine/threonine-protein
  			kinase, Transferase
  AL161983		hypothetical protein		474	4442
  		MGC39820
  AL161994	HEI10	cyclin B1 interacting	Ubl conjugation pathway, Ligase,	475	4443
  		protein 1	Nuclear protein, Metal-binding, Zinc,
  			Coiled coil, Zinc-finger,
  			Phosphorylation, Ubl conjugation
  AL162013	PLXNA1	Homo sapiens	Hypothetical protein	476	4444
  		mRNA; cDNA
  		DKFZp761P19121
  		(from clone
  		DKFZp761P19121);
  		partial cds.
  AL162039		MOB1, Mps One		477	4445
  		Binder kinase
  		activator-like 1A
  		(yeast)
  AL162062	LOC91010	formin-like 3	Hypothetical protein	478	4446
  AL353934	MUS81	MUS81	Endonuclease, Hypothetical protein	479	4447
  		endonuclease
  		homolog (yeast)
  AL353952	PI4KII	phosphatidylinositol	Hypothetical protein, Kinase	480	4448
  		4-kinase type II
  AL353953	FLJ13055	lipid phosphate	Hypothetical protein	481	4449
  		phosphatase-related
  		protein type
  2
  AL355708	NEO1	neogenin homolog 1	Cell adhesion, Repeat, Signal,	482	4450
  		(chicken)	Transmembrane, Immunoglobulin
  			domain, Glycoprotein, Alternative
  			splicing
  AW190932_RC	GPI	xl66g09.x1	Gluconeogenesis, Glycolysis,	483	4451
  		NCI_CGAP_Pan1	Isomerase, Growth factor, Cytokine,
  		Homo sapienscDNA	Disease mutation, 3D-structure,
  		clone	Hypothetical protein
  		IMAGE: 2679712 3′,
  		mRNA sequence.
  AW273216_RC		ring finger protein	Hypothetical protein, Metal-binding,	484	4452
  		149	Zinc, Zinc-finger
  AW419203_RC	KIAA0601	amine oxidase	Hypothetical protein	485	4453
  		(flavin containing)
  		domain 2
  AW673036_RC	PPP1R3B	hypothetical protein	Hypothetical protein	486	4454
  		LOC286044
  BE671663_RC	EVIN2	epidermodysplasia	Transmembrane, Hypothetical	487	4455
  		verruciformis 2	protein
  BE672528_RC		cyclin-dependent		488	4456
  		kinase 6
  Contig10037_RC		hypothetical protein	Hypothetical protein	489	4457
  		DKFZp667C165
  Contig1007_RC	LOC51754	hypothetical protein	Hypothetical protein	490	4458
  		LOC283070
  Contig10162_RC	MGC14276	hypothetical protein	Hypothetical protein	491	4459
  		MGC14276
  Contig1030_RC	FLJ00026	dedicator of	Guanine-nucleotide releasing factor	492	4460
  		cytokinesis 8
  Contig10363_RC	MRF2	AT rich interactive	Hypothetical protein	493	4461
  		domain 5B (MRF1-
  		like)
  Contig10373_RC		hypothetical protein	Hypothetical protein	494	4462
  		MGC21854
  Contig10418_RC		Transcribed		495	4463
  		sequences
  Contig10429_RC	DKFZp434H2111	hypothetical protein	Hypothetical protein	496	4464
  		DKFZp434H2111
  Contig10531_RC		microtubule-	Microtubule, Cytoskeleton, Repeat,	497	4465
  		associated protein	Alternative splicing, Acetylation,
  		tau	Phosphorylation, Glycoprotein,
  			Polymorphism, Disease mutation,
  			Alzheimer's disease, 3D-structure,
  			Hypothetical protein
  Contig1056_RC	LOC57106	K562 cell-derived	Hypothetical protein	498	4466
  		leucine-zipper-like
  		protein
  1
  Contig1061_RC		KIAA0924 protein	Hypothetical protein, Metal-binding,	499	4467
  			Nuclear protein, Zinc, Zinc-finger
  Contig10629_RC	PERQ1	PERQ amino acid	Hypothetical protein	500	4468
  		rich, withGYF
  		domain
  1
  Contig1063_RC	TRIM33	Homo sapienscDNA	Hypothetical protein	501	4469
  		FLJ35131 fis, clone
  		PLACE6008824.
  Contig10670_RC		Transcribed		502	4470
  		sequences
  Contig10690_RC		spleen tyrosine	Transferase, Tyrosine-protein	503	4471
  		kinase	kinase, ATP-binding,
  			Phosphorylation, SH2 domain,
  			Repeat, Alternative splicing, 3D-
  			structure
  Contig10750_RC		Transcribed		504	4472
  		sequences
  Contig10844_RC		CDNA FLJ31150 fis,	Hypothetical protein	505	4473
  		clone
  		IMR322001534
  Contig11012_RC		leukocyte-derived	Aminopeptidase	506	4474
  		arginine
  		aminopeptidase
  Contig11075_RC	NFASC	neurofascin	Cell adhesion, Repeat, Signal,	507	4475
  			Transmembrane, Immunoglobulin
  			domain, Glycoprotein, Alternative
  			splicing, Polymorphism, Hypothetical
  			protein
  Contig11266_RC		Transcribed		508	4476
  		sequence with
  		moderate similarity
  		to protein
  		ref: NP_054848.1
  		(H. sapiens)
  		PRO0478 protein
  		[Homo sapiens]
  Contig112_RC	NICE-4	NICE-4 protein	Hypothetical protein	509	4477
  Contig1146_RC	LOC90550	chromosome 10	Hypothetical protein	510	4478
  		open reading frame
  		42
  Contig11_RC		hypothetical protein	Hypothetical protein	511	4479
  		LOC90462
  Contig12140_RC		Transcribed		512	4480
  		sequences
  Contig12201_RC		splicing factor,	Nuclear protein, RNA-binding,	513	4481
  		arginine/serine-rich 5	mRNA splicing, Alternative splicing,
  			Repeat, Phosphorylation,
  			Polymorphism, Plasmid
  Contig12540_RC		Transcribed		514	4482
  		sequences
  Contig12750_RC		hypothetical protein	Hypothetical protein	515	4483
  		LOC257106
  Contig12755_RC	GCN1L1	homeodomain	Transferase, Serine/threonine-	516	4484
  		interacting protein	protein kinase, ATP-binding,Nuclear
  		kinase
  2	protein, Alternative splicing
  Contig12820_RC	FLJ21709	nucleotide-binding	Hypothetical protein	517	4485
  		oligomerization
  		domains 27
  Contig12855	MAPK8IP2	MRNA; cDNA	Kinase, SH3 domain, Alternative	518	4486
  		DKFZp434J0428	splicing
  		(from clone
  		DKFZp434J0428)
  Contig1295_RC	MDS033	protein F25965	Transmembrane, Golgi stack,	519	4487
  			Endoplasmic reticulum
  Contig13165_RC	B4GALT6	UDP-	Transferase, Glycosyltransferase,	520	4488
  		Gal:betaGlcNAc	Glycoprotein, Transmembrane,
  		beta 1,4-	Signal-anchor, Golgi stack,
  		galactosyltransferase,	Manganese, Magnesium, Calcium,
  		polypeptide 6	Multigene family
  Contig13387_RC	FLJ21458	hypothetical protein	Hypothetical protein	521	4489
  		FLJ21458
  Contig13480_RC		Transcribed		522	4490
  		sequences
  Contig1351_RC		zinc finger protein	Hypothetical protein, Metal-binding,	523	4491
  		325	Nuclear protein, Zinc, Zinc-finger,
  			Transcription regulation, DNA-
  			binding, Repeat
  Contig13609_RC		Transcribed		524	4492
  		sequences
  Contig13643_RC		Transcribed		525	4493
  		sequences
  Contig1366_RC	DC-TM4F2	tetraspanin similar to	Hypothetical protein,	526	4494
  		TM4SF9	Transmembrane
  Contig13766_RC		Transcribed		527	4495
  		sequences
  Contig1386_RC	SEMA4B	sema domain,	Transmembrane, Immunoglobulin	528	4496
  		immunoglobulin	domain, Multigene family,
  		domain (Ig),	Neurogenesis, Developmental
  		transmembrane	protein, Glycoprotein, Signal,
  		domain (TM) and	Polymorphism
  		short cytoplasmic
  		domain,
  		(semaphorin) 4B
  Contig1389_RC	ITPR1	mitogen-activated	ATP-binding, Kinase, Transferase,	529	4497
  		protein kinase 9	Serine/threonine-protein kinase,
  			Phosphorylation, Alternative splicing
  Contig14039_RC	FOXE3	forkhead box E3	Transcription regulation, DNA-	530	4498
  			binding, Nuclear protein
  Contig1403_RC	LBH	likely ortholog of	Hypothetical protein	531	4499
  		mouse limb-bud and
  		heart gene
  Contig14172		vitelliform macular	Iron storage, Iron, Metal-binding, 3D-	532	4500
  		dystrophy (Best	structure, Transport, Ion transport,
  		disease, bestrophin)	Ionic channel, Chloride channel,
  			Calcium, Alternative splicing,
  			Disease mutation, Polymorphism,
  			Vision, Transmembrane,
  			Phosphorylation
  Contig14197_RC		Transcribed		533	4501
  		sequences
  Contig1422_RC		hypothetical protein	Hypothetical protein	534	4502
  		FLJ38426
  Contig14282_RC		Transcribed		535	4503
  		sequences
  Contig14433_RC		Transcribed		536	4504
  		sequences
  Contig1447_RC	EFG1	mitochondrial	Elongation factor, Protein	537	4505
  		elongation factor G1	biosynthesis, Mitochondrion, Transit
  			peptide, GTP-binding
  Contig14520_RC		Transcribed		538	4506
  		sequences
  Contig14555_RC		Transcribed		539	4507
  		sequences
  Contig14581_RC		Transcribed		540	4508
  		sequences
  Contig14625_RC	FLJ22021	hypothetical protein	Repeat, WD repeat	541	4509
  		FLJ22021
  Contig1462_RC	C11orf15	chromosome 11	Transmembrane	542	4510
  		open reading frame
  		15
  Contig14658_RC		zx08b09.s1		543	4511
  		Soares_total_fetus_Nb2HF8_9w
  		Homo
  		sapienscDNA clone
  		IMAGE: 785849 3′,
  		mRNA sequence.
  Contig14720_RC		Transcribed		544	4512
  		sequences
  Contig14797_RC		Transcribed		545	4513
  		sequences
  Contig14899_RC	LOC146853	LOC146853		546	4514
  Contig1505_RC	MGC4308	hypothetical protein		547	4515
  		MGC4308
  Contig151_RC	ELKS	CDNA FLJ31750 fis,	Hypothetical protein	548	4516
  		clone
  		NT2RI2007406
  Contig15267_RC		Transcribed		549	4517
  		sequences
  Contig15281_RC		Chediak-Higashi	Protein transport, Transport, Repeat,	550	4518
  		syndrome 1	WD repeat, Disease mutation,
  			Alternative splicing
  Contig1540_RC	ACTB	serine	Transferase, Acyltransferase,	551	4519
  		palmitoyltransferase,	Transmembrane, Pyridoxal
  		long chain base	phosphate,Endoplasmic reticulum
  		subunit
  2
  Contig15580_RC		LOC401124		552	4520
  		(LOC401124),
  		mRNA
  Contig15607_RC		Transcribed		553	4521
  		sequences
  Contig15635_RC		Transcribed		554	4522
  		sequences
  Contig15647_RC		Transcribed		555	4523
  		sequences
  Contig15674_RC		Transcribed		556	4524
  		sequences
  Contig15898_RC		Transcribed		557	4525
  		sequence with weak
  		similarity to protein
  		ref: NP_055301.1
  		(H. sapiens)
  		neuronal thread
  		protein [Homo
  		sapiens]
  Contig16192_RC		Transcribed		558	4526
  		sequence with
  		moderate similarity
  		to protein
  		ref: NP_110386.1
  		(H. sapiens) nuclear
  		receptor binding
  		factor-2 [Homo
  		sapiens]
  Contig1619_RC	NAPB	N-ethylmaleimide-	Hypothetical protein	559	4527
  		sensitive factor
  		attachment protein,
  		beta
  Contig1620_RC	PPP1R16A	protein phosphatase	ANK repeat, Repeat, Coiled coil,	560	4528
  		1, regulatory	Lipoprotein, Prenylation, Membrane
  		(inhibitor) subunit
  		16A
  Contig16217_RC		Transcribed		561	4529
  		sequences
  Contig1632_RC	MGC17921	chromosome 14	Alternative splicing	562	4530
  		open reading frame
  		31
  Contig16376_RC	DKFZP564B1162	hypothetical protein	Hypothetical protein	563	4531
  		DKFZp564B1162
  Contig16437_RC		Transcribed		564	4532
  		sequences
  Contig16440_RC		Transcribed		565	4533
  		sequences
  Contig16441_RC		Transcribed		566	4534
  		sequences
  Contig16447_RC	C16orf44	chromosome 16	Hypothetical protein	567	4535
  		open reading frame
  		44
  Contig16530_RC		Transcribed		568	4536
  		sequences
  Contig16736_RC		Clone	Hypothetical protein	569	4537
  		IMAGE: 5561763,
  		mRNA
  Contig16772_RC		Transcribed		570	4538
  		sequences
  Contig16786_RC		Transcribed		571	4539
  		sequences
  Contig1682_RC	RCP	Rab coupling protein	Hypothetical protein	572	4540
  Contig16908_RC	MGC42174	hypothetical protein	Hypothetical protein	573	4541
  		MGC42174
  Contig16931_RC	YR-29	TGF beta-inducible	Nuclear protein	574	4542
  		nuclear protein 1
  Contig1699_RC	FLJ12438	hypothetical protein	Hypothetical protein	575	4543
  		FLJ12438
  Contig17017_RC		Transcribed		576	4544
  		sequences
  Contig17084_RC		DEAD (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	577	4545
  		Asp) box polypeptide	Hypothetical protein
  		31
  Contig17109_RC		Similar to Protein		578	4546
  		C20orf27
  		(LOC390690),
  		mRNA
  Contig17356_RC		hypothetical protein	Hypothetical protein	579	4547
  		FLJ13611
  Contig17607_RC		Transcribed		580	4548
  		sequences
  Contig1789_RC	LAGY	homeodomain-only	Hypothetical protein, DNA-binding,	581	4549
  		protein	Homeobox, Nuclear protein
  Contig178_RC		syntrophin,beta 2	Actin-binding, Cytoskeleton,	582	4550
  		(dystrophin-	Microtubule, Calcium-binding,
  		associated protein	Calmodulin-binding, Membrane,
  		A1, 59 kDa, basic	Phosphorylation, Repeat,
  		component 2)	Polymorphism, Multigene family,
  			Alternative splicing
  Contig17982_RC		hypothetical protein	Hypothetical protein	583	4551
  		FLJ14624
  Contig1798_RC	MOX2	antigen identified by	Antigen, Neurone, T-cell, Signal,	584	4552
  		monoclonal antibody	Transmembrane, Immunoglobulin
  		MRC OX-2	domain, Glycoprotein, Alternative
  			splicing
  Contig18246_RC		oz78a12.x1		585	4553
  		Soares_senescent_fibroblasts_NbHSF
  		Homo sapienscDNA
  		clone
  		IMAGE: 1681438 3′,
  		mRNA sequence.
  Contig18286_RC		pellino 3 alpha	Alternative splicing	586	4554
  Contig18476_RC		Homo sapiens, clone		587	4555
  		IMAGE: 4830091,
  		mRNA.
  Contig18493_RC		oj35b09.s1		588	4556
  		NCI_CGAP_Lu5
  		Homo sapienscDNA
  		clone
  		IMAGE: 1500281 3′,
  		mRNA sequence.
  Contig18504_RC	OR52K3P	olfactory receptor,	Hypothetical protein	589	4557
  		family 52, subfamily
  		K,member 3
  		pseudogene
  Contig19023_RC		yf45a10.s2 Soares		590	4558
  		fetal liver spleen
  		1NFLSHomo
  		sapienscDNA clone
  		IMAGE: 129786 3′,
  		mRNA sequence.
  Contig19064_RC		hypothetical protein		591	4559
  		LOC340351
  Contig19127_RC	FLJ31295	hypothetical protein	Metal-binding, Zinc, Zinc-finger,	592	4560
  		FLJ31295	Hypothetical protein
  Contig19210_RC		Transcribed		593	4561
  		sequences
  Contig1924_RC	C20orf11	chromosome	20	Coiled coil	594	4562
  		open reading frame
  		11
  Contig19333_RC		Transcribed		595	4563
  		sequences
  Contig1951	GNPAT	MRNA; cDNA	Transferase, Acyltransferase,	596	4564
  		DKFZp686J23256	Peroxisome, Membrane, Rhizomelic
  		(from clone	chondrodysplasia punctata, Disease
  		DKFZp686J23256)	mutation
  Contig19700_RC		Transcribed		597	4565
  		sequences
  Contig19715_RC		Transcribed		598	4566
  		sequences
  Contig1990_RC	LOC92799	hypothetical protein	Repeat, WD repeat, Hypothetical	599	4567
  		BC007653	protein
  Contig19918_RC		Transcribed		600	4568
  		sequences
  Contig1991_RC	PGA5	pepsinogen	5, group	Hydrolase, Aspartyl protease,	601	4569
  		I (pepsinogen A)	Digestion, Zymogen, Signal,
  			Phosphorylation, 3D-structure,
  			Polymorphism
  Contig19931_RC		Transcribed		602	4570
  		sequences
  Contig20370_RC		Transcribed		603	4571
  		sequences
  Contig20391_RC		Transcribed		604	4572
  		sequence with
  		strong similarity to
  		protein pir: EFHU1
  		(H. sapiens) EFHU1
  		translation
  		elongation factor
  		eEF-1 alpha-1 chain -
  		human
  Contig20427_RC		Transcribed		605	4573
  		sequences
  Contig20600_RC		CDNA FLJ34654 fis,		606	4574
  		clone
  		KIDNE2018294
  Contig20617_RC		CDNA FLJ34031 fis,		607	4575
  		clone
  		FCBBF2003895
  Contig20830_RC		Homo sapienscDNA		608	4576
  		FLJ13550 fis, clone
  		PLACE1007111.
  Contig20843_RC		Transcribed		609	4577
  		sequences
  Contig20864_RC	FLJ22529	hypothetical protein	Hypothetical protein	610	4578
  		FLJ22529
  Contig20913_RC	FLJ12785	hypothetical protein	Hypothetical protein	611	4579
  		FLJ12785
  Contig20979_RC		hypothetical protein		612	4580
  		MGC35555
  Contig21098_RC		Msx-interacting-zinc	Multigene family, Zinc-finger,	613	4581
  		finger	Nuclear protein, DNA-binding, Metal-
  			binding, Alternative splicing
  Contig21116_RC		Transcribed		614	4582
  		sequences
  Contig21200_RC		Transcribed		615	4583
  		sequences
  Contig21268_RC		Similar to		616	4584
  		hypothetical protein
  		FLJ35867
  		(LOC342357),
  		mRNA
  Contig2143_RC	KIAA1771	dedicator of	Hypothetical protein, Guanine-	617	4585
  		cytokinesis 7	nucleotide releasing factor,
  			Alternative splicing
  Contig21627_RC		CDNA FLJ39637 fis,	Hypothetical protein	618	4586
  		clone
  		SMINT2003003
  Contig21787_RC		Transcribed		619	4587
  		sequences
  Contig2179_RC	FLJ32452	hypothetical protein	Hypothetical protein	620	4588
  		FLJ32452
  Contig21839_RC		ow70g11.s1		621	4589
  		Soares_fetal_liver_spleen_1NFLS_S1
  		Homo sapienscDNA
  		clone
  		IMAGE: 1652228 3′,
  		mRNA sequence.
  Contig21847_RC	KSP37	Ksp37 protein		622	4590
  Contig21891_RC	FLJ13231	hypothetical protein	Hypothetical protein	623	4591
  		FLJ13231
  Contig21904		immunoglobulin		624	4592
  		superfamily,member 2
  Contig21997_RC		Transcribed		625	4593
  		sequences
  Contig22003_RC		Transcribed		626	4594
  		sequences
  Contig22025_RC	FLJ10111	v-akt murine	Hypothetical protein, ATP-binding,	627	4595
  		thymoma viral	Transferase, Serine/threonine-
  		oncogene homolog 1	protein kinase, Phosphorylation,
  			Nuclear protein, Kinase
  Contig22418_RC	PTP4A3	protein tyrosine		628	4596
  		phosphatase type
  		IVA,member 3
  Contig22526_RC		Transcribed		629	4597
  		sequences
  Contig22551_RC		Transcribed		630	4598
  		sequences
  Contig2263_RC	KIAA1949	KIAA1949	Hypothetical protein	631	4599
  Contig22844_RC	DKFZp434H2111	hypothetical protein	Hypothetical protein	632	4600
  		DKFZp434H2111
  Contig22901_RC		AGENCOURT_6640943		633	4601
  		NIH_MGC_99
  		Homo sapienscDNA
  		clone
  		IMAGE: 5434077 5′,
  		mRNA sequence.
  Contig23240_RC		hypothetical protein	Hypothetical protein	634	4602
  		FLJ12525
  Contig23263_RC	NR5A1	Homo sapienscDNA	Receptor, Transcription regulation,	635	4603
  		FLJ33539 fis, clone	DNA-binding, Nuclear protein, Zinc-
  		BRAMY2007610,	finger, Disease mutation,
  		highly similar to	Hypothetical protein
  		STEROIDOGENIC
  		FACTOR 1.
  Contig23280		lecithin-cholesterol	Cholesterol metabolism, Lipid	636	4604
  		acyltransferase	metabolism, Transferase,
  			Acyltransferase, Signal,
  			Glycoprotein, Polymorphism,
  			Disease mutation
  Contig23299_RC	P5	BTG3 associated	Hypothetical protein	637	4605
  		nuclear protein
  Contig2339_RC	FLJ21032	stearoyl-CoA	Hypothetical protein	638	4606
  		desaturase 4
  Contig23423_RC		Transcribed		639	4607
  		sequences
  Contig23525_RC	KIAA0140	similar to CG9643-	Hypothetical protein	640	4608
  		PA
  Contig23547_RC		Clone		641	4609
  		IMAGE: 5214442,
  		mRNA
  Contig23593_RC		Transcribed		642	4610
  		sequences
  Contig23604_RC		carnitine O-	Transferase, Acyltransferase, Fatty	643	4611
  		octanoyltransferase	acid metabolism, Transport,
  			Peroxisome
  Contig23667_RC		WD repeat and	Nuclear protein, DNA-binding,	644	4612
  		HMG-box DNA	Repeat, WDrepeat
  		binding protein
  1
  Contig24090		CDNA FLJ37425 fis,		645	4613
  		clone
  		BRAWH2001530
  Contig24094_RC		CDNA FLJ30598 fis,		646	4614
  		clone
  		BRAWH2009263
  Contig24098_RC		glutamate receptor,	Receptor, Signal, Transmembrane,	647	4615
  		ionotropic, N-methyl	Postsynaptic membrane, Calcium,
  		D-aspartate 2D	Glycoprotein, Ionic channel,
  			Magnesium
  Contig2429_RC		FLJ40142 protein	Hypothetical protein	648	4616
  Contig24450_RC		Transcribed		649	4617
  		sequences
  Contig24453_RC		Transcribed		650	4618
  		sequences
  Contig24600_RC		Transcribed		651	4619
  		sequences
  Contig25041_RC		yx89b03.s1 Soares		652	4620
  		melanocyte 2NbHM
  		Homo sapienscDNA
  		clone
  		IMAGE: 268877 3′,
  		mRNA sequence.
  Contig25058_RC		Transcribed		653	4621
  		sequences
  Contig2505_RC	GLTP	glycolipid transfer	Transport, Lipid transport, Repeat,	654	4622
  		protein	Acetylation
  Contig25107_RC		ferredoxin 1	Metal-binding, Iron-sulfur, Iron, 2Fe—2S,	655	4623
  			Electron transport,
  			Mitochondrion, Transit peptide
  Contig25126_RC		Transcribed		656	4624
  		sequences
  Contig2531_RC	FLJ12484	hypothetical protein	Hypothetical protein	657	4625
  		FLJ12484
  Contig25332_RC	GDF11	cytokine induced	Nuclear protein, DNA-binding,	658	4626
  		protein 29 kDa	Transcription, Transcription
  			regulation, Translation regulation
  Contig25362_RC	DKFZP566A1524	hypothetical protein	Hypothetical protein	659	4627
  		DKFZp566A1524
  Contig25429_RC		Transcribed		660	4628
  		sequences
  Contig25435_RC	FLJ10803	hypothetical protein	Hypothetical protein	661	4629
  		FLJ10803
  Contig2544	FLJ11526	hypothetical protein	Hypothetical protein	662	4630
  		FLJ11526
  Contig25546_RC	CCT6A	itchy homolog E3	Ubl conjugation pathway, Ligase,	663	4631
  		ubiquitin protein	Nuclear protein, Repeat,
  		ligase (mouse)	Phosphorylation, Alternative splicing
  Contig25595_RC	KIAA1618	KIAA1618	Hypothetical protein	664	4632
  Contig256	PSMD11	wt73b11.x1	Proteasome	665	4633
  		Soares_thymus_NHFTh
  		Homo sapiens
  		cDNA clone
  		IMAGE: 2513085 3′
  		similar to
  		TR: Q26195 Q26195
  		PVA1 GENE.;
  		mRNA sequence.
  Contig25610_RC		CDNA FLJ31796 fis,		666	4634
  		clone
  		NT2RI2008841
  Contig25744_RC		Transcribed		667	4635
  		sequences
  Contig2576_RC	DKFZP564O1664	hypothetical protein	Hypothetical protein	668	4636
  		DKFZp564O1664
  Contig25770_RC		Clone		669	4637
  		IMAGE: 4817413,
  		mRNA
  Contig25783_RC		Clone		670	4638
  		IMAGE: 5555626,
  		mRNA
  Contig2578_RC	ORF1-FL49	putative nuclear	Nuclear protein	671	4639
  		protein ORF1-FL49
  Contig25827_RC	FLJ13848	hypothetical protein	Hypothetical protein	672	4640
  		FLJ13848
  Contig2584_RC		ribonuclease P	Hydrolase, Nuclear protein, tRNA	673	4641
  		(14 kD)	processing
  Contig25861_RC		Transcribed		674	4642
  		sequences
  Contig25960_RC	DKFZP564B0769	chromosome 6 open	Hypothetical protein	675	4643
  		reading frame 111
  Contig26014_RC	SYTL3	synaptotagmin-like 3		676	4644
  Contig26019_RC		methionyl	Aminopeptidase, Hypothetical	677	4645
  		aminopeptidase 2	protein, Hydrolase, Cobalt, 3D-
  			structure
  Contig26059_RC		Transcribed		678	4646
  		sequences
  Contig2608	SLC2A4RG	SLC2A4 regulator	Transcription regulation, DNA-	679	4647
  			binding, Nuclear protein, Zinc-finger,
  			Metal-binding, Alternative splicing
  Contig26170_RC		Transcribed		680	4648
  		sequences
  Contig26332_RC		Transcribed		681	4649
  		sequences
  Contig263_RC	MGC12435	chromosome 14		682	4650
  		open reading frame
  		168
  Contig26405_RC	TSLL2	immunoglobulin	Immunoglobulin domain	683	4651
  		superfamily, member
  		4C
  Contig26416_RC		Transcribed		684	4652
  		sequences
  Contig26461_RC		Transcribed		685	4653
  		sequences
  Contig2647_RC	BCAT1	branched chain	Transferase, Aminotransferase,	686	4654
  		aminotransferase 1,	Hypothetical protein, Branched-chain
  		cytosolic	amino acid biosynthesis, Pyridoxal
  			phosphate
  Contig2648_RC	MGC15407	similar to RIKEN		687	4655
  		cDNA 4931428D14
  		gene
  Contig2657_RC	MGC16207	hypothetical protein	Hypothetical protein	688	4656
  		MGC16207
  Contig26622_RC	BIC	BIC transcript		689	4657
  Contig26706_RC		CDNA FLJ43676 fis,		690	4658
  		clone
  		SYNOV4009129
  Contig26998_RC		WD repeatdomain 1	Repeat, WD repeat, Actin-binding,	691	4659
  			Cytoskeleton, Alternative splicing,
  			Polymorphism, Hypothetical protein
  Contig27060_RC		Transcribed		692	4660
  		sequence with
  		moderate similarity
  		to protein pdb: 1LBG
  		(E. coli) B Chain B,
  		Lactose Operon
  		Repressor Bound To
  		21-Base Pair
  		Symmetric Operator
  		Dna, Alpha Carbons
  		Only
  Contig27084_RC		CDNA FLJ45493 fis,		693	4661
  		clone
  		BRTHA2008598
  Contig27124_RC		CDNA FLJ42250 fis,		694	4662
  		clone
  		TKIDN2007828
  Contig27145_RC		Transcribed		695	4663
  		sequences
  Contig27228_RC		amyloid beta (A4)	Hypothetical protein	696	4664
  		precursor protein-
  		binding, family B,
  		member 1
  		interacting protein
  Contig2728_RC		zinc finger protein	Hypothetical protein, Metal-binding,	697	4665
  		596	Zinc, Zinc-finger
  Contig27338_RC		Transcribed		698	4666
  		sequences
  Contig27386_RC	C7orf13	chromosome 7 open		699	4667
  		reading frame 13
  Contig27542_RC		Transcribed		700	4668
  		sequences
  Contig27558_RC	FLJ13163	MRNA; cDNA	Hypothetical protein, Kinase	701	4669
  		DKFZp779J2459
  		(from clone
  		DKFZp779J2459)
  Contig27725_RC		Transcribed		702	4670
  		sequences
  Contig27765_RC		potassium inwardly-	Hypothetical protein, Ionic channel,	703	4671
  		rectifying channel,	Ion transport, Voltage-gated
  		subfamily J, member	channel, Transmembrane,
  		15	Potassium transport
  Contig27776_RC		hypothetical protein	Hypothetical protein	704	4672
  		FLJ21106
  Contig27797_RC		DnaJ (Hsp40)	Chaperone, Repeat, Zinc, Metal-	705	4673
  		homolog, subfamily	binding, Prenylation, Lipoprotein,
  		A,member 2	Membrane, Multigene family
  Contig27820_RC		Transcribed		706	4674
  		sequences
  Contig27837_RC		Transcribed		707	4675
  		sequence with weak
  		similarity to protein
  		ref: NP_060265.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20378 [Homo
  		sapiens]
  Contig27896_RC		HSPC009 protein		708	4676
  Contig27915_RC	MGC40042	hypothetical protein	Hypothetical protein	709	4677
  		MGC40042
  Contig27977_RC		Transcribed		710	4678
  		sequences
  Contig28024_RC	KIAA0955	caspase recruitment	Apoptosis, Nuclear protein,	711	4679
  		domain family,	Alternative splicing,Hypothetical
  		member
  8	protein
  Contig28050_RC		Homo sapienscDNA		712	4680
  		FLJ35764 fis, clone
  		TESTI2004906,
  		weakly similar to
  		H. sapiensmRNA for
  		SIRP-beta1.
  Contig2811_RC	C8orf2	Homo sapiens	Transmembrane, Alternative splicing	713	4681
  		mRNA; cDNA
  		DKFZp667H242
  		(from clone
  		DKFZp667H242);
  		complete cds.
  Contig28164_RC		Transcribed		714	4682
  		sequences
  Contig28181_RC		ns17h07.s1		715	4683
  		NCI_CGAP_GCB1
  		Homo sapienscDNA
  		clone
  		IMAGE: 1183933 3′,
  		mRNA sequence.
  Contig28229_RC		Transcribed		716	4684
  		sequences
  Contig2823_RC	FLJ23499	chromosome 11	Hypothetical protein	717	4685
  		open reading frame 1
  Contig28286_RC		Transcribed		718	4686
  		sequences
  Contig28298_RC	NUP62	UI-H-BI0p-abm-b-	Nuclear protein, Transport,	719	4687
  		04-0-UI.s1	Glycoprotein, Coiled coil, Repeat,
  		NCI_CGAP_Sub2	Polymorphism
  		Homo sapienscDNA
  		clone
  		IMAGE: 2712150 3′,
  		mRNA sequence.
  Contig28522_RC		Clone 24653 mRNA		720	4688
  		sequence
  Contig28567_RC		Transcribed		721	4689
  		sequences
  Contig2857_RC	DKFZp761G2113	hypothetical protein	Hypothetical protein	722	4690
  		DKFZp761G2113
  Contig28707_RC	ADAMTS13	a disintegrin-like and	Protease, Hypothetical protein,	723	4691
  		metalloprotease	Signal
  		(reprolysin type) with
  		thrombospondin type
  		1 motif, 13
  Contig28760_RC		cyclin-dependent		724	4692
  		kinase 6
  Contig28766_RC		Transcribed		725	4693
  		sequences
  Contig28787_RC		hypothetical protein	Hypothetical protein	726	4694
  		LOC120526
  Contig2883_RC	RALY	Clone	Ribonucleoprotein, RNA-binding,	727	4695
  		IMAGE: 5285100,	Nuclear protein, Antigen, Alternative
  		mRNA	splicing, Polymorphism
  Contig28947_RC	CDC25A	cell division cycle	Cell division, Mitosis, Hydrolase,	728	4696
  		25A	Alternative splicing, Multigene family,
  			3D-structure, Hypothetical protein
  Contig28949		Clone		729	4697
  		IMAGE: 5268292,
  		mRNA
  Contig28996_RC		NHL repeat		730	4698
  		containing 1
  Contig29171_RC		CDNA FLJ11544 fis,		731	4699
  		clone
  		HEMBA1002826
  Contig29207_RC		chromosome 20		732	4700
  		open reading frame
  		78
  Contig29284_RC		Transcribed		733	4701
  		sequences
  Contig292_RC	FLJ22386	leucine zipper	Hypothetical protein	734	4702
  		domain protein
  Contig2930_RC	DAB2	CDNA FLJ35517 fis,	Alternative splicing, Phosphorylation	735	4703
  		clone
  		SPLEN2000698
  Contig29349_RC		Transcribed		736	4704
  		sequences
  Contig29362_RC		hypothetical protein	Hypothetical protein	737	4705
  		LOC338692
  Contig29373_RC		24b2/STAC2 protein		738	4706
  Contig29569_RC		hypothetical protein	Hypothetical protein	739	4707
  		MGC29898
  Contig29732_RC		hypothetical protein		740	4708
  		LOC338758
  Contig29749_RC	LOC85028	PNAS-123		741	4709
  Contig29780_RC		Transcribed		742	4710
  		sequences
  Contig29802_RC		programmed cell	Calcium-binding, Repeat, Apoptosis	743	4711
  		death 6
  Contig29860_RC	NFAM1	NFAT activation	Hypothetical protein, Signal,	744	4712
  		molecule 1	Transmembrane, Immunoglobulin
  			domain, Phosphorylation
  Contig2986_RC	EEG1	C1q domain	Hypothetical protein	745	4713
  		containing 1
  Contig29887_RC	DKFZp434J0617	hypothetical protein	Hypothetical protein	746	4714
  		DKFZp434J0617
  Contig29890_RC	FLJ32449	ankyrin repeat	Hypothetical protein, ANK repeat,	747	4715
  		domain 23	Repeat
  Contig29901_RC		proteasome	Proteasome, Hydrolase, Protease,	748	4716
  		(prosome,	Acetylation, Alternative splicing,
  		macropain) subunit,	Phosphorylation, Threonine protease
  		alpha type, 3
  Contig29921_RC	FLJ22570	Dok-like protein	Hypothetical protein	749	4717
  Contig29940_RC	CMYA1	cardiomyopathy	Hypothetical protein	750	4718
  		associated 1
  Contig29954_RC	CATSPER2	Clone		751	4719
  		IMAGE: 5294645,
  		mRNA
  Contig29955_RC		zj86d08.s1		752	4720
  		Soares_fetal_liver_spleen_1NFLS_S1
  		Homo sapienscDNA
  		clone
  		IMAGE: 461775 3′,
  		mRNA sequence.
  Contig29995_RC		Transcribed		753	4721
  		sequences
  Contig30052_RC	C18B11	C18B11 homolog	Hypothetical protein	754	4722
  		(44.9 kD)
  Contig30109_RC	PRKWNK4	protein kinase, lysine	Hypothetical protein, ATP-binding,	755	4723
  		deficient 4	Transferase, Kinase,
  			Serine/threonine-protein kinase
  Contig30154_RC		Transcribed		756	4724
  		sequence with
  		moderate similarity
  		to protein sp: P39194
  		(H. sapiens)
  		ALU7_HUMAN Alu
  		subfamily SQ
  		sequence
  		contamination
  		warning entry
  Contig3015_RC		pleckstrin homology		757	4725
  		domain containing,
  		family A
  		(phosphoinositide
  		binding specific)
  		member 2
  Contig30209_RC	FLJ12649	hypothetical protein	Hypothetical protein	758	4726
  		FLJ12649
  Contig30378_RC	FLJ10178	hypothetical protein	Hypothetical protein	759	4727
  		FLJ10178
  Contig30474_RC	VIT	vitrin	Hypothetical protein	760	4728
  Contig30484_RC		Transcribed		761	4729
  		sequences
  Contig30496_RC	ZNF219	LOC400176	Transcription regulation, DNA-	762	4730
  		(LOC387957),	binding, Zinc-finger, Metal-binding,
  		mRNA	Nuclear protein, Repeat
  Contig30736_RC		Transcribed		763	4731
  		sequences
  Contig30811_RC	PRKRA	MRNA; cDNA	Kinase	764	4732
  		DKFZp686G1498
  		(from clone
  		DKFZp686G1498)
  Contig30840_RC	LOC63929	hypothetical protein	Hypothetical protein	765	4733
  		LOC63929
  Contig30934_RC	MGC33993	hypothetical protein	Hypothetical protein, Metal-binding,	766	4734
  		MGC33993	Zinc, Zinc-finger
  Contig3094_RC	PINK1	PTEN induced	Hypothetical protein, ATP-binding,	767	4735
  		putative kinase 1	Kinase, Serine/threonine-protein
  			kinase, Transferase
  Contig30977_RC		hypothetical protein		768	4736
  		LOC154790
  Contig30989_RC	MGC10744	hypothetical protein	Hypothetical protein	769	4737
  		MGC10744
  Contig31057_RC		Transcribed		770	4738
  		sequences
  Contig31186_RC	HNRPDL	heterogeneous	Nucleocapsid, Ribonucleoprotein	771	4739
  		nuclear
  		ribonucleoprotein D-
  		like
  Contig31361_RC		dedicator of	Hypothetical protein, Guanine-	772	4740
  		cytokinesis 7	nucleotide releasing factor,
  			Alternative splicing
  Contig31366_RC	LNPEP	hypothetical protein	Hypothetical protein	773	4741
  		FLJ39485
  Contig31421_RC		thyroid hormone	Proteasome, Ubl conjugation	774	4742
  		receptor interactor	pathway, Ligase
  		12
  Contig31449_RC		Transcribed		775	4743
  		sequence with weak
  		similarity to protein
  		sp: P39195
  		(H. sapiens)
  		ALU8_HUMAN Alu
  		subfamily SX
  		sequence
  		contamination
  		warning entry
  Contig3147_RC	MUM2	trafficking protein	Transport, Endoplasmic reticulum,	776	4744
  		particle complex 1	Golgi stack, Disease mutation
  Contig31482_RC		Transcribed		777	4745
  		sequences
  Contig31495		thyroid hormone	Antigen, Golgi stack, Coiled coil,	778	4746
  		receptor interactor	Chromosomal translocation,
  		11	Hypothetical protein
  Contig31513_RC		Transcribed		779	4747
  		sequences
  Contig31525_RC		Transcribed		780	4748
  		sequence with weak
  		similarity to protein
  		ref: NP_079364.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ13241 [Homo
  		sapiens]
  Contig31587_RC		Human full-length	Plasmid	781	4749
  		cDNA 5-PRIME end
  		of clone
  		CS0DK007YB08 of
  		HeLa cells ofHomo
  		sapiens(human)
  Contig31597_RC	PDE4DIP	chromosome 1	Hypothetical protein	782	4750
  		amplified sequence 3
  Contig31661_RC		hypothetical protein	Hypothetical protein, Repeat, WD	783	4751
  		FLJ10385	repeat
  Contig31664_RC	MGC26979	hypothetical protein	Hypothetical protein	784	4752
  		MGC26979
  Contig31699_RC		CDNA FLJ27273 fis,		785	4753
  		clone TMS00761
  Contig31740_RC	PFN1	hypothetical protein	Metal-binding, Zinc, Zinc-finger,	786	4754
  		LOC285345	Transcription regulation, DNA-
  			binding, Nuclear protein, Repeat
  Contig31864_RC		FERM domain	Hypothetical protein	787	4755
  		containing 3
  Contig31906_RC		similar to	Hypothetical protein	788	4756
  		hypothetical protein
  		FLJ13659
  Contig31911_RC		hypothetical protein	Hypothetical protein	789	4757
  		LOC349136
  Contig32027_RC		CDNA FLJ46867 fis,		790	4758
  		clone
  		UTERU3012293,
  		weakly similar to
  		Homo sapienszinc
  		finger protein 14
  		(KOX 6) (ZNF14)
  Contig32059_RC	MGC17919	zinc finger and BTB	Zinc, Hypothetical protein, Metal-	791	4759
  		domain containing 8	binding, Zinc-finger
  Contig32081_RC		Full length insert		792	4760
  		cDNA clone
  		YP77A07
  Contig32103_RC		Clone		793	4761
  		IMAGE: 4689481,
  		mRNA
  Contig32123_RC		Similar to ataxin 2		794	4762
  		binding protein 1
  		isoform gamma;
  		hexaribonucleotide
  		binding protein 1
  		(LOC339162),
  		mRNA
  Contig32185_RC		intimal thickness-		795	4763
  		related receptor
  Contig3228_RC	VMP1	hypothetical protein	Hypothetical protein	796	4764
  		LOC283680
  Contig32322_RC		quaking homolog,	Hypothetical protein	797	4765
  		KH domain RNA
  		binding (mouse)
  Contig32323_RC		hypothetical protein	Hypothetical protein	798	4766
  		FLJ13105
  Contig32335_RC		Transcribed		799	4767
  		sequences
  Contig32377_RC		ubiquitin specific	Protease	800	4768
  		protease 51
  Contig32431_RC		Transcribed		801	4769
  		sequences
  Contig3250_RC	LOC92399	mitochondrial	Hypothetical protein	802	4770
  		ribosome recycling
  		factor
  Contig32540_RC		Transcribed		803	4771
  		sequences
  Contig32550_RC	ZFP93	zinc finger protein	Transcription regulation, DNA-	804	4772
  		235	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  Contig32637_RC		RAB27A, member	GTP-binding, Lipoprotein,	805	4773
  		RAS oncogene	Prenylation, Alternative splicing,
  		family	Disease mutation
  Contig32757	FLJ21069	hypothetical protein	Hypothetical protein, ANK repeat,	806	4774
  		FLJ21069	Repeat
  Contig32825_RC		polymerase (RNA) III		807	4775
  		(DNA directed)
  		(32 kD)
  Contig32920	FUBP1	nexilin (F actin	Hypothetical protein	808	4776
  		binding protein)
  Contig33062_RC		chromosome 17	Hypothetical protein	809	4777
  		open reading frame
  		31
  Contig3311_RC	MGC13186	hypothetical protein	Hypothetical protein, ATP-binding	810	4778
  		MGC13186
  Contig33127_RC		Sequence 161 from		811	4779
  		Patent WO0220754.
  Contig3313	FLJ23153	likely ortholog of	Hypothetical protein	812	4780
  		mouse tumor
  		necrosis-alpha-
  		induced adipose-
  		related protein
  Contig33188_RC		Transcribed		813	4781
  		sequences
  Contig33207_RC		Transcribed		814	4782
  		sequences
  Contig33224_RC		Transcribed		815	4783
  		sequences
  Contig33273_RC		chromodomain	DNA-binding, Helicase, Hypothetical	816	4784
  		helicase DNA	protein, ATP-binding, Hydrolase
  		binding protein 1-like
  Contig3331_RC	MKI67IP	MKI67 (FHA		817	4785
  		domain) interacting
  		nucleolar
  		phosphoprotein
  Contig33334_RC		Transcribed		818	4786
  		sequences
  Contig33369_RC		Transcribed		819	4787
  		sequence with weak
  		similarity to protein
  		ref: NP_062553.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ11267 [Homo
  		sapiens]
  Contig33394_RC	FLJ37318	ubiquitin specific	Hypothetical protein	820	4788
  		protease 54
  Contig3344	MGC2835	DEAD (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	821	4789
  		Asp) box polypeptide	Hypothetical protein
  		54
  Contig33442_RC		MOB1, Mps One	Hypothetical protein	822	4790
  		Binder kinase
  		activator-like 2A
  		(yeast)
  Contig33464_RC		Similar to bA304I5.1		823	4791
  		(novel lipase)
  		(LOC340654),
  		mRNA
  Contig33540_RC	SEMA3F	ob92d09.s1	Signal, Immunoglobulin domain,	824	4792
  		NCI_CGAP_GCB1	Multigene family, Glycoprotein,
  		Homo sapienscDNA	Polymorphism
  		clone
  		IMAGE: 1338833 3′,
  		mRNA sequence.
  Contig33574_RC		Transcribed		825	4793
  		sequences
  Contig3359_RC		neuralized-like	Hypothetical protein	826	4794
  		(Drosophila)
  Contig33703_RC	FLJ21438	hypothetical protein	Hypothetical protein	827	4795
  		FLJ21438
  Contig33741_RC	FLJ12428	DEP domain	Hypothetical protein	828	4796
  		containing 6
  Contig33760_RC		chromosome	9 open		829	4797
  		reading frame 71
  Contig33790_RC		jun dimerization	DNA-binding, Nuclear protein	830	4798
  		protein 2
  Contig33810_RC	FLJ31528	hypothetical protein	Hypothetical protein	831	4799
  		FLJ31528
  Contig33831_RC		Transcribed		832	4800
  		sequences
  Contig33852_RC	OPRL1	opiate receptor-like 1	G-protein coupled receptor,	833	4801
  			Transmembrane, Glycoprotein,
  			Phosphorylation, Lipoprotein,
  			Palmitate, Alternative splicing
  Contig33888_RC		ow44c09.x1		834	4802
  		Soares_parathyroid_tumor_NbHPA
  		Homo sapienscDNA
  		clone
  		IMAGE: 1649680 3′,
  		mRNA sequence.
  Contig3390_RC	FLJ12619	chromosome 6 open	Hypothetical protein	835	4803
  		reading frame 62
  Contig33951_RC		nuclear pore	Nuclear protein, Transport	836	4804
  		complex protein
  Contig33967_RC		Transcribed		837	4805
  		sequences
  Contig33987		hypothetical protein	Hypothetical protein	838	4806
  		KIAA1109
  Contig33996_RC		Transcribed		839	4807
  		sequences
  Contig34019_RC	MGC15827	hypothetical protein	Hypothetical protein	840	4808
  		MGC15827
  Contig34051_RC		Transcribed		841	4809
  		sequences
  Contig34090_RC		Transcribed		842	4810
  		sequences
  Contig340_RC	PPP1R15B	protein phosphatase	Hypothetical protein	843	4811
  		1, regulatory
  		(inhibitor) subunit
  		15B
  Contig34118_RC		Transcribed		844	4812
  		sequences
  Contig34231_RC		yd77f12.s1 Soares		845	4813
  		fetal liver spleen
  		1NFLSHomo
  		sapienscDNA clone
  		IMAGE: 114287 3′,
  		mRNA sequence.
  Contig34286_RC		Transcribed		846	4814
  		sequences
  Contig34291_RC		nuclear receptor	Transcription regulation, Receptor,	847	4815
  		subfamily 3, group	Trans-acting factor, Nuclear protein,
  		C,member 1	DNA-binding, Steroid-binding, Zinc-
  		(glucocorticoid	finger, Phosphorylation, Ubl
  		receptor)	conjugation, Alternative initiation,
  			Alternative splicing, Polymorphism,
  			Disease mutation
  Contig34302_RC		hypothetical protein		848	4816
  		LOC150166
  Contig34303_RC	SFXN5	sideroflexin 5	Transport, Iron transport, Iron,	849	4817
  			Mitochondrion, Transmembrane
  Contig34350_RC		CDNA FLJ45384 fis,		850	4818
  		clone
  		BRHIP3021987
  Contig34470_RC		similar to kinesin	Hypothetical protein	851	4819
  		family member 21A;
  		N-5 kinesin
  Contig34554_RC		CDNA FLJ33367 fis,		852	4820
  		clone
  		BRACE2005661
  Contig34593_RC		Transcribed		853	4821
  		sequences
  Contig34607_RC		ym49g02.s1 Soares		854	4822
  		infant brain 1NIB
  		Homo sapienscDNA
  		clone IMAGE: 51586
  		3′, mRNA sequence.
  Contig34634_RC	GCN1L1	homeodomain	Transferase, Serine/threonine-	855	4823
  		interacting protein	protein kinase, ATP-binding,Nuclear
  		kinase
  2	protein, Alternative splicing
  Contig34672_RC		Transcribed		856	4824
  		sequences
  Contig3474_RC		CDNA: FLJ22541		857	4825
  		fis, clone HSI00130
  Contig34768_RC		chromosome 21	Hypothetical protein	858	4826
  		open reading frame
  		59
  Contig34779_RC		SH3-domain kinase	SH3 domain, Repeat, Membrane,	859	4827
  		binding protein 1	Nuclear protein, Coiled coil,
  			Polymorphism, Alternative splicing
  Contig34880_RC		Transcribed		860	4828
  		sequences
  Contig3495_RC	MGC45416	hypothetical protein	Hypothetical protein	861	4829
  		MGC45416
  Contig34983_RC		Transcribed		862	4830
  		sequences
  Contig34998_RC	TMLHE	CDNA FLJ25895 fis,	Hypothetical protein	863	4831
  		clone CBR03553
  Contig34999_RC		periplakin	Keratinization, Repeat, Coiled coil,	864	4832
  			Cytoskeleton, Structural protein
  Contig35002_RC	FLJ12994	hypothetical protein	Hypothetical protein	865	4833
  		FLJ12994
  Contig35018_RC		zr44a03.s1		866	4834
  		Soares_NhHMPu_S1
  		Homo sapiens
  		cDNA clone
  		IMAGE: 666220 3′,
  		mRNA sequence.
  Contig35043		Transcribed		867	4835
  		sequences
  Contig35052_RC		pituitary tumor-	Transmembrane, Nuclear protein	868	4836
  		transforming 1
  		interacting protein
  Contig35076_RC		Sequence 226 from		869	4837
  		Patent WO0220754.
  Contig35094_RC	FLJ21478	NOD9 protein	Hypothetical protein	870	4838
  Contig35163_RC		Similar to		871	4839
  		hypothetical protein
  		MG11009.4
  		(LOC285344),
  		mRNA
  Contig35182_RC		qb88b05.x1		872	4840
  		Soares_fetal_heart_NbHH19W
  		Homo
  		sapienscDNA clone
  		IMAGE: 1707153 3′,
  		mRNA sequence.
  Contig35187_RC	ARL4	ADP-ribosylation	GTP-binding, Multigene family,	873	4841
  		factor-like 4	Nuclear protein
  Contig35251_RC		CDNA: FLJ22719		874	4842
  		fis, clone HSI14307
  Contig35425_RC		hypothetical protein	Hypothetical protein	875	4843
  		LOC285831
  Contig35435_RC	FLJ23447	hypothetical protein	Hypothetical protein	876	4844
  		FLJ23447
  Contig35576_RC		Transcribed		877	4845
  		sequences
  Contig35608_RC		df54a02.y1 Morton		878	4846
  		Fetal CochleaHomo
  		sapienscDNA clone
  		IMAGE: 2487051 5′,
  		mRNA sequence.
  Contig35635_RC	TAGAP	T-cell activation	Hypothetical protein	879	4847
  		GTPase activating
  		protein
  Contig35661_RC	DSCR1L2	Down syndrome	Alternative splicing	880	4848
  		critical region gene
  		1-like 2
  Contig35685_RC	FLJ13117	spermatogenesis	Hypothetical protein	881	4849
  		associated, serine-
  		rich 2
  Contig35700_RC		CDNA clone		882	4850
  		IMAGE: 6702802,
  		partial cds
  Contig35713_RC		FIS		883	4851
  Contig35799_RC		centaurin,beta 2	GTPase activation, Repeat, ANK	884	4852
  			repeat, Zinc-finger
  Contig35874_RC		Transcribed		885	4853
  		sequences
  Contig35896_RC		signal transducer	Hypothetical protein, Repeat, WD	886	4854
  		and activator of	repeat
  		transcription
  3
  		interactingprotein 1
  Contig35940	KIAA1733	RPEL repeat	Hypothetical protein	887	4855
  		containing 1
  Contig35958_RC	MGC13071	hypothetical protein	Hypothetical protein, Metal-binding,	888	4856
  		MGC13071	Nuclear protein, Zinc, Zinc-finger
  Contig35976_RC		family with sequence	Signal	889	4857
  		similarity 3, member C
  Contig3597_RC	LENG5	leukocyte receptor	Receptor, Hypothetical protein	890	4858
  		cluster (LRC)
  		member 5
  Contig36020_RC	MGC15634	hypothetical protein	Hypothetical protein	891	4859
  		MGC15634
  Contig36075_RC		Transcribed		892	4860
  		sequences
  Contig36104_RC	CCT6A	laa10b09.x1 8 5	Chaperone, ATP-binding, Multigene	893	4861
  		week embryo	family
  		anterior tongue 8 5
  		EATHomosapiens
  		cDNA
  3′, mRNA
  		sequence.
  Contig36106_RC	NCL	hypothetical protein	Hypothetical protein	894	4862
  		LOC157697
  Contig36125_RC		Transcribed		895	4863
  		sequences
  Contig36129_RC	MGC4707	hypothetical protein	Hypothetical protein	896	4864
  		LOC283989
  Contig3612_RC	KIAA1802	chromosome 13	Hypothetical protein, Metal-binding,	897	4865
  		open reading frame 8	Zinc, Zinc-finger
  Contig36152_RC		sterile alpha motif	Hypothetical protein, ANK repeat,	898	4866
  		domain containing 6	Repeat
  Contig36169_RC	DKFZp547E052	hypothetical protein	Hypothetical protein	899	4867
  		DKFZp547E052
  Contig36178_RC		sialyltransferase 9	Transferase, Glycosyltransferase,	900	4868
  		(CMP-	Glycoprotein, Transmembrane,
  		NeuAc:lactosylceramide	Signal-anchor, Golgi stack
  		alpha-2,3-
  		sialyltransferase;
  		GM3 synthase)
  Contig36190_RC		Transcribed		901	4869
  		sequences
  Contig36193_RC		inositol
  1,4,5-	Receptor, Transmembrane,	902	4870
  		triphosphate	Phosphorylation, Ionic channel, Ion
  		receptor,type 1	transport, Calcium channel
  Contig36195		Full length insert		903	4871
  		cDNA clone
  		ZD73D05
  Contig3626_RC	FLJ13855	hypothetical protein	Hypothetical protein, Ligase, Ubl	904	4872
  		FLJ13855	conjugation pathway
  Contig36323_RC	SFXN5	sideroflexin 5	Transport, Iron transport, Iron,	905	4873
  			Mitochondrion, Transmembrane
  Contig36359_RC		Transcribed		906	4874
  		sequences
  Contig36369_RC		we24d02.x1		907	4875
  		NCI_CGAP_Lu24
  		Homo sapienscDNA
  		clone
  		IMAGE: 2342019 3′,
  		mRNA sequence.
  Contig36409_RC		Transcribed		908	4876
  		sequences
  Contig36512_RC		Transcribed		909	4877
  		sequences
  Contig36525	ARX	aristaless related	Homeobox, DNA-binding,	910	4878
  		homeobox	Developmental protein, Nuclear
  			protein, Transcription regulation,
  			Disease mutation, Triplet repeat
  			expansion, Epilepsy
  Contig36617_RC		chromosome 6 open		911	4879
  		reading frame 182
  Contig36622_RC		Transcribed		912	4880
  		sequences
  Contig36628		HANP1		913	4881
  Contig36634_RC	FLJ39514	sec1 family domain	Hypothetical protein	914	4882
  		containing 2
  Contig36720_RC		Transcribed		915	4883
  		sequences
  Contig36761_RC	FLJ23403	hypothetical protein	Hypothetical protein	916	4884
  		FLJ23403
  Contig36803_RC	FLJ13952	sortingnexin 22	Hypothetical protein, Transport,	917	4885
  			Protein transport
  Contig36805_RC	MGC15435	zinc finger, BED	Zinc-finger	918	4886
  		domain containing 3
  Contig36810		CDNA FLJ37425 fis,		919	4887
  		clone
  		BRAWH2001530
  Contig36876_RC		Homo sapienscDNA		920	4888
  		FLJ32044 fis, clone
  		NTONG2000985.
  Contig36879_RC		Clone		921	4889
  		IMAGE: 4753714,
  		mRNA
  Contig36888_RC		suppression of	Hypothetical protein	922	4890
  		tumorigenicity 7 like
  Contig36939_RC		Transcribed		923	4891
  		sequences
  Contig3695_RC	MGC17330	HGFL gene	Hypothetical protein, Glycoprotein,	924	4892
  			Kringle
  Contig36973_RC	AGMAT	Homo sapiens	Putrescine biosynthesis, Spermidine	925	4893
  		cDNA: FLJ23384 fis,	biosynthesis, Hydrolase,
  		clone HEP16468.	Manganese, Mitochondrion, Transit
  			peptide
  Contig36976_RC	DIBD1	disrupted in bipolar	Hypothetical protein	926	4894
  		affective disorder 1
  Contig36997_RC	bioref	zinc finger protein	Transcription regulation, DNA-	927	4895
  		481	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  Contig37016_RC	ING5	inhibitor of growth	Hypothetical protein	928	4896
  		family,member 5
  Contig37025_RC		CDNA FLJ41484 fis,		929	4897
  		clone
  		BRTHA2003030
  Contig37029_RC	FLJ23153	likely ortholog of	Hypothetical protein	930	4898
  		mouse tumor
  		necrosis-alpha-
  		induced adipose-
  		relatedprotein
  Contig37037_RC		chromosome
  13		931	4899
  		open reading frame
  		25
  Contig37082_RC	MGC2408	hypothetical protein	Hypothetical protein	932	4900
  		MGC2408
  Contig37140_RC		membrane protein,	Hypothetical protein, SH3 domain	933	4901
  		palmitoylated 7
  		(MAGUK p55
  		subfamily member 7)
  Contig37142_RC		Homo sapienscDNA		934	4902
  		FLJ12163 fis, clone
  		MAMMA1000594.
  Contig37219	MDN1	MDN1, midasin	Chaperone, ATP-binding, Repeat,	935	4903
  		homolog (yeast)	Nuclear protein
  Contig37262		Clone	Hypothetical protein	936	4904
  		IMAGE: 5263527,
  		mRNA
  Contig37300_RC	KIAA1904	KIAA1904 protein	Hypothetical protein	937	4905
  Contig37306_RC	MUC16	mucin 16	Hypothetical protein	938	4906
  Contig3734_RC	RPS8	Clone	Ribosomal protein	939	4907
  		IMAGE: 4249217,
  		mRNA
  Contig37361_RC		Transcribed		940	4908
  		sequences
  Contig37364_RC		Transcribed		941	4909
  		sequences
  Contig37368_RC		nemo like kinase	ATP-binding, Kinase,	942	4910
  			Serine/threonine-protein kinase,
  			Transferase
  Contig37569_RC		CDNA FLJ26339 fis,		943	4911
  		clone HRT02975
  Contig37660_RC	ADAM6	a disintegrin and		944	4912
  		metalloproteinase
  		domain
  6
  Contig37736_RC	RAD1	Transcribed	Hypothetical protein, Ribosome	945	4913
  		sequence with	biogenesis, Nuclear protein, Cell
  		moderate similarity	cycle, Exonuclease
  		to protein
  		ref: NP_060312.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20489 [Homo
  		sapiens]
  Contig37763_RC		Transcribed		946	4914
  		sequence with
  		moderate similarity
  		to protein
  		ref: NP_002945.1
  		(H. sapiens)
  		ubiquitin and
  		ribosomal protein
  		S27a precursor;
  		ubiquitincarboxyl
  		extension protein
  80;
  		40S ribosomal
  		protein S27a;
  		ubiquitin; ubiquitin-
  		CEP80 [Homo
  		sapiens]
  Contig37764_RC		qa65f01.x1		947	4915
  		Soares_fetal_heart_NbHH19W
  		Homo
  		sapienscDNA clone
  		IMAGE: 1691641 3′,
  		mRNA sequence.
  Contig37895_RC		yh88d01.s1 Soares		948	4916
  		placenta Nb2HP
  		Homo sapienscDNA
  		clone
  		IMAGE: 136801 3′,
  		mRNA sequence.
  Contig37950_RC		qz91d12.x1		949	4917
  		Soares_pregnant_uterus_NbHPU
  		Homo
  		sapienscDNA clone
  		IMAGE: 2041943 3′,
  		mRNA sequence.
  Contig37958	KAI1	hypothetical protein	Glycoprotein, Transmembrane,	950	4918
  		LOC284023	Antigen
  Contig37991_RC	LOC133308	hypothetical protein	Hypothetical protein	951	4919
  		BC009732
  Contig38043_RC		hypothetical protein		952	4920
  		LOC199675
  Contig38093_RC		Transcribed		953	4921
  		sequences
  Contig380_RC	KIAA1724	selenoprotein I, 1	Hypothetical protein, Transferase,	954	4922
  			Transmembrane, Selenium,
  			Selenocysteine
  Contig38117_RC		Transcribed		955	4923
  		sequences
  Contig38155_RC		Transcribed		956	4924
  		sequences
  Contig38169_RC	FLJ13984	hypothetical protein	Hypothetical protein	957	4925
  		FLJ13984
  Contig3820_RC	LOC56898	dehydrogenase/reductase	Oxidoreductase, Hypothetical protein	958	4926
  		(SDR family)
  		member 6
  Contig38285_RC	FLJ10462	male sterility domain	Hypothetical protein	959	4927
  		containing 1
  Contig38288_RC	DKFZp762A2013	quiescin Q6-like 1	Hypothetical protein, Signal	960	4928
  Contig382_RC	NLI-IF	CTD (carboxy-	Hypothetical protein, Nuclear protein	961	4929
  		terminal domain,
  		RNA polymerase II,
  		polypeptide A) small
  		phosphatase 1
  Contig38320_RC		Transcribed		962	4930
  		sequences
  Contig38321_RC		Transcribed		963	4931
  		sequences
  Contig3834_RC		MRNA; cDNA		964	4932
  		DKFZp686K14148
  		(from clone
  		DKFZp686K14148)
  Contig38398_RC		Transcribed		965	4933
  		sequences
  Contig38493_RC		CDNA FLJ42010 fis,		966	4934
  		clone
  		SPLEN2032036
  Contig38581_RC		anaphase promoting	Ubl conjugation pathway, Cell cycle,	967	4935
  		complex subunit 1	Cell division, Mitosis, Repeat
  Contig38603_RC		Transcribed		968	4936
  		sequences
  Contig38604_RC		CDNA FLJ25042 fis,	Hypothetical protein	969	4937
  		clone CBL03351
  Contig38654_RC		solute carrier family		970	4938
  		28 (sodium-coupled
  		nucleoside
  		transporter),
  		member 3
  Contig38669_RC	HS2ST1	heparan sulfate 2-O-	Hypothetical protein, Transferase	971	4939
  		sulfotransferase 1
  Contig38714_RC		Transcribed		972	4940
  		sequences
  Contig38721_RC	MGC35163	sterile alpha motif	Hypothetical protein	973	4941
  		domain containing 3
  Contig38724_RC		Clone		974	4942
  		IMAGE: 5275753,
  		mRNA
  Contig38726_RC		SWI/SNF related,	Hypothetical protein	975	4943
  		matrix associated,
  		actin dependent
  		regulator of
  		chromatin, subfamily
  		e, member 1
  Contig38731_RC		frizzled homolog 2	Multigene family, G-protein coupled	976	4944
  		(Drosophila)	receptor, Transmembrane,
  			Developmental protein, Wnt
  			signaling pathway, Glycoprotein,
  			Signal
  Contig38778	TRIM7	tripartite motif-	Zinc-finger, Zinc, Coiled coil, Metal-	977	4945
  		containing 7	binding, Polymorphism, Alternative
  			splicing
  Contig38803_RC		Rho GTPase	GTPase activation, SH3-binding, 3D-	978	4946
  		activating protein 1	structure
  Contig38877		zv94e09.s1		979	4947
  		Soares_NhHMPu_S1
  		Homo sapiens
  		cDNA clone
  		IMAGE: 767464 3′,
  		mRNA sequence.
  Contig38944_RC		Transcribed		980	4948
  		sequences
  Contig39008_RC	MYCL1	v-myc	Nuclear protein, DNA-binding, Proto-	981	4949
  		myelocytomatosis	oncogene
  		viral oncogene
  		homolog
  1, lung
  		carcinoma derived
  		(avian)
  Contig39043_RC		zl77f02.s1		982	4950
  		Stratagene colon
  		(#937204)Homo
  		sapienscDNA clone
  		IMAGE: 510651 3′,
  		mRNA sequence.
  Contig39048_RC		TAFA2 protein	Hypothetical protein	983	4951
  Contig39116_RC	a1/3GTP	alpha-1,3-	Glycosyltransferase, Transferase	984	4952
  		galactosyltransferase
  		pseudogene
  Contig3920_RC	SP1	Sp1 transcription	Hypothetical protein, Transcription	985	4953
  		factor	regulation, Activator, Zinc-finger,
  			Metal-binding, DNA-binding, Nuclear
  			protein, Repeat, Glycoprotein, 3D-
  			structure
  Contig39236	FLJ00026	Homo sapiens,	Hypothetical protein, Guanine-	986	4954
  		Similar to RIKEN	nucleotide releasing factor
  		cDNA 5830472H07
  		gene, clone
  		MGC: 39702
  		IMAGE: 5271738,
  		mRNA, complete
  		cds.
  Contig39249	THBS3	thrombospondin 3	Glycoprotein, Cell adhesion,	987	4955
  			Calcium-binding, Repeat, EGF-like
  			domain, Signal
  Contig39287_RC		Transcribed		988	4956
  		sequence with
  		moderate similarity
  		to protein pir: E54024
  		(H. sapiens) E54024
  		protein kinase
  Contig39297_RC	LOC148898	hypothetical protein	Hypothetical protein	989	4957
  		BC007899
  Contig39364_RC	UPF3B	UPF3 regulator of		990	4958
  		nonsense transcripts
  		homolog B (yeast)
  Contig39403_RC		hypothetical protein	Hypothetical protein	991	4959
  		FLJ34790
  Contig3940_RC	C9orf19	chromosome 9 open	Hypothetical protein	992	4960
  		reading frame 19
  Contig39448_RC		N-acetylneuraminate		993	4961
  		pyruvate lyase
  		(dihydrodipicolinate
  		synthase)
  Contig39496_RC	FLJ22501	Hermansky-Pudlak	Hypothetical protein	994	4962
  		syndrome 6
  Contig39545_RC	MTIF3	general transcription	Transcription regulation, Zinc-finger,	995	4963
  		factor IIIA	Metal-binding, DNA-binding, RNA-
  			binding, Repeat, Nuclear protein,
  			Polymorphism
  Contig39603_RC	CNOT3	CCR4-NOT	Hypothetical protein	996	4964
  		transcription
  		complex, subunit 3
  Contig39626_RC	STK35	serine/threonine	Hypothetical protein, Transferase,	997	4965
  		kinase 35	Serine/threonine-protein kinase,
  			ATP-binding, Phosphorylation
  Contig39702_RC		similar to Putative	Hypothetical protein	998	4966
  		protein C21orf56
  Contig39739_RC	CDK9	Full length insert	Transferase, Serine/threonine-	999	4967
  		cDNA clone	protein kinase, ATP-binding, Nuclear
  		ZA91F08	protein, Polymorphism
  Contig39797_RC	TRIPIN	tripin	Hypothetical protein	1000	4968
  Contig39810_RC		hypothetical protein	Hypothetical protein	1001	4969
  		MGC43690
  Contig39878_RC	BOP	SET and MYND	Transcription regulation, Repressor,	1002	4970
  		domain containing 1	DNA-binding, Nuclear protein, Zinc-
  			finger, Metal-binding
  Contig39933_RC	LOC90693	Sequence 2 from	Hypothetical protein	1003	4971
  		Patent WO0220754.
  Contig39989_RC	MGC14289	similar to RIKEN		1004	4972
  		cDNA 1200014N16
  		gene
  Contig40015_RC		Transcribed		1005	4973
  		sequence with
  		moderate similarity
  		to protein pdb: 1LBG
  		(E. coli) B Chain B,
  		Lactose Operon
  		Repressor Bound To
  		21-Base Pair
  		Symmetric Operator
  		Dna, Alpha Carbons
  		Only
  Contig40026_RC		CDNA FLJ12935 fis,		1006	4974
  		clone
  		NT2RP2004982
  Contig40053_RC	HNRPD	heterogeneous	Nuclear protein, RNA-binding, DNA-	1007	4975
  		nuclear	binding, Ribonucleoprotein, Repeat,
  		ribonucleoprotein D	Transcription regulation, Telomere,
  		(AU-rich element	Alternative splicing, 3D-structure
  		RNA binding protein
  		1, 37 kDa)
  Contig40055_RC		Transcribed		1008	4976
  		sequences
  Contig40069_RC		Transcribed		1009	4977
  		sequences
  Contig40093_RC		fatty acid binding	Transport, Lipid-binding, Acetylation,	1010	4978
  		protein 3, muscle	Phosphorylation, 3D-structure
  		and heart
  		(mammary-derived
  		growth inhibitor)
  Contig40094_RC	DKFZp434I099	hypothetical protein	Hypothetical protein	1011	4979
  		DKFZp434I099
  Contig40128_RC		hypoxia-inducible	Transcription regulation, Activator,	1012	4980
  		factor 1, alpha	Nuclear protein, DNA-binding,
  		subunit (basic helix-	Alternative splicing, Repeat,
  		loop-helix	Acetylation, Hydroxylation,
  		transcription factor)	Phosphorylation, S-nitrosylation,
  			Polymorphism, 3D-structure
  Contig40184	SLC2A1	solute carrier family	Transmembrane, Sugar transport,	1013	4981
  		2 (facilitated glucose	Transport, Glycoprotein, Multigene
  		transporter),	family, Disease mutation, 3D-
  		member 1	structure
  Contig40212_RC	CD5	CD5 antigen (p56-62)	Signal, Transmembrane,	1014	4982
  			Glycoprotein, T-cell, Repeat
  Contig40237_RC	FLJ12525	hypothetical protein	Hypothetical protein	1015	4983
  		FLJ12525
  Contig40252_RC		CDNA clone	Hypothetical protein	1016	4984
  		IMAGE: 3462401,
  		partial cds
  Contig40340_RC		hypothetical protein	Hypothetical protein	1017	4985
  		FLJ11000
  Contig40389_RC		Similar to RIKEN		1018	4986
  		cDNA 3830422K02
  		(LOC387755),
  		mRNA
  Contig404		Mesenchymal stem		1019	4987
  		cell protein DSC96
  		mRNA, partial cds
  Contig40405_RC	MGC10818	chromosome 6 open	Hypothetical protein	1020	4988
  		reading frame 148
  Contig40410		tc14e12.x1	Hypothetical protein	1021	4989
  		Soares_NhHMPu_S1
  		Homo sapiens
  		cDNA clone
  		IMAGE: 2063854 3′,
  		mRNA sequence.
  Contig40450_RC		THAP domain	Hypothetical protein	1022	4990
  		containing 9
  Contig40552_RC	FLJ25348	hypothetical protein	Hypothetical protein	1023	4991
  		FLJ25348
  Contig40651_RC		Transcribed		1024	4992
  		sequences
  Contig40676_RC		Sequence 60 from		1025	4993
  		Patent WO0220754.
  Contig40830_RC	TSGA14	testis specific, 14	Hypothetical protein	1026	4994
  Contig40832_RC		Transcribed		1027	4995
  		sequences
  Contig40897_RC	DKFZP434J037	likely ortholog of rat	Hypothetical protein, ATP-binding,	1028	4996
  		SNF1/AMP-activated	Kinase, Serine/threonine-protein
  		protein kinase	kinase, Transferase
  Contig40960_RC	FLJ36991	zinc finger protein	Hypothetical protein, Metal-binding,	1029	4997
  		565	Nuclear protein, Zinc, Zinc-finger
  Contig40965_RC	MGC4504	hypothetical protein	Hypothetical protein	1030	4998
  		MGC4504
  Contig40967_RC		LOC389388		1031	4999
  		(LOC389388),
  		mRNA
  Contig41005_RC		Transcribed		1032	5000
  		sequence with
  		strong similarity to
  		protein pdb: 1BGM
  		(E. coli) O Chain O,
  		Beta-Galactosidase
  Contig41035		golgi phosphoprotein 4		1033	5001
  Contig41041_RC		CDNA FLJ32274 fis,		1034	5002
  		clone
  		PROST2000036
  Contig41080_RC		Transcribed		1035	5003
  		sequences
  Contig41086_RC		forkhead box P1	Hypothetical protein, Transcription	1036	5004
  			regulation, DNA-binding, Zinc-finger,
  			Metal-binding, Nuclear protein,
  			Alternative splicing
  Contig41094_RC	EDG8	endothelial	Hypothetical protein, Receptor	1037	5005
  		differentiation,
  		sphingolipid G-
  		protein-coupled
  		receptor, 8
  Contig41121_RC	FCRH3	Fc receptor-like	Immunoglobulin domain, Receptor	1038	5006
  		protein 3
  Contig41209_RC	FLJ21432	adiponectin receptor 2	Fatty acid metabolism, Lipid	1039	5007
  			metabolism, Receptor,
  			Transmembrane
  Contig41226_RC		MRNA; cDNA	Hypothetical protein	1040	5008
  		DKFZp434O232
  		(from clone
  		DKFZp434O232)
  Contig412_RC	FLJ22233	Homo sapienscDNA	Hypothetical protein	1041	5009
  		FLJ36755 fis, clone
  		UTERU2018180,
  		weakly similar to
  		Na+/Ca2+,K+-
  		exchanging protein
  		homolog C13D9.8.
  Contig41301	LOC152217	hypothetical protein	Hypothetical protein	1042	5010
  		BC007882
  Contig41421_RC	FLJ36156	piwi-like 2	Hypothetical protein	1043	5011
  		(Drosophila)
  Contig41448_RC		dynamin 1-like		1044	5012
  Contig41537	MGC20496	methylmalonic	Transferase, Mitochondrion, Transit	1045	5013
  		aciduria (cobalamin	peptide, Polymorphism, Disease
  		deficiency) type B	mutation
  Contig41560_RC	CPT1A	carnitine	Transferase, Acyltransferase,	1046	5014
  		palmitoyltransferase	Mitochondrion, Outer membrane,
  		1A (liver)	Fatty acid metabolism, Transport,
  			Transmembrane, Multigene family
  Contig41612_RC		hypothetical protein	Hypothetical protein	1047	5015
  		LOC132241
  Contig41618_RC		Clone	Hypothetical protein	1048	5016
  		IMAGE: 5315196,
  		mRNA
  Contig41638_RC	SLC26A8	solute carrier family		1049	5017
  		26,member 8
  Contig41656_RC		Similar to Eph		1050	5018
  		receptor A7, clone
  		IMAGE: 5273054,
  		mRNA
  Contig41701_RC		Transcribed		1051	5019
  		sequences
  Contig41748_RC	ELMO3	engulfment and cell	Apoptosis, Phagocytosis,	1052	5020
  		motility 3 (ced-12	Cytoskeleton, Membrane, SH3-
  		homolog,C. elegans)	binding
  Contig41774_RC		Transcribed		1053	5021
  		sequences
  Contig41781_RC	ARHGEF7	Rho guanine	Guanine-nucleotide releasing factor,	1054	5022
  		nucleotide exchange	SH3 domain, Alternative splicing,
  		factor (GEF) 7	3D-structure, Hypothetical protein
  Contig41828_RC		Clone		1055	5023
  		IMAGE: 5310874,
  		mRNA
  Contig41864_RC	ZFP106	zinc finger protein	Hypothetical protein, Metal-binding,	1056	5024
  		106 homolog	Repeat, WD repeat, Zinc, Zinc-finger
  		(mouse)
  Contig41869_RC	SFRS3	splicing factor,	Nuclear protein, RNA-binding,	1057	5025
  		arginine/serine-rich 3	mRNA splicing, Alternative splicing,
  			Phosphorylation, Repeat
  Contig41903_RC	FLJ21657	hypothetical protein	Hypothetical protein	1058	5026
  		FLJ21657
  Contig41923_RC	OATL1	ornithine	Transferase, Aminotransferase	1059	5027
  		aminotransferase-
  		like 1
  Contig41936_RC	MSL3L1	male-specific lethal	Chromatin regulator, Nuclear	1060	5028
  		3-like 1 (Drosophila)	protein, Transcription regulation,
  			Alternative splicing
  Contig41983_RC		ym35b12.s1 Soares		1061	5029
  		infant brain 1NIB
  		Homo sapienscDNA
  		clone IMAGE: 50144
  		3′, mRNA sequence.
  Contig42005_RC		splicing factor,	Nuclear protein, RNA-binding,	1062	5030
  		arginine/serine-rich	mRNA splicing, Repeat
  		11
  Contig42006_RC		RasGEF domain	Hypothetical protein	1063	5031
  		family, member 1B
  Contig42012_RC		zinc finger, DHHC	Transmembrane, Zinc-finger	1064	5032
  		domain containing
  		21
  Contig42014_RC	RNTRE	USP6 N-terminal like	Hypothetical protein	1065	5033
  Contig42076_RC	FLJ39091	zinc binding alcohol	Hypothetical protein	1066	5034
  		dehydrogenase,
  		domain containing 1
  Contig42105_RC		MRNA; cDNA		1067	5035
  		DKFZp686P24244
  		(from clone
  		DKFZp686P24244)
  Contig42146_RC		chromosome 19	Hypothetical protein	1068	5036
  		open reading frame
  		12
  Contig42154_RC	FLJ11795	hypothetical protein	Hypothetical protein	1069	5037
  		FLJ11795
  Contig42174	FLJ33215	hypothetical protein	Hypothetical protein	1070	5038
  		FLJ33215
  Contig42177_RC		zinc finger, DHHC	Hypothetical protein,	1071	5039
  		domain containing	Transmembrane, Zinc-finger
  		19
  Contig42185_RC	TLR8	toll-like receptor 8	Hypothetical protein, Receptor,	1072	5040
  			Immune response, Inflammatory
  			response, Signal, Transmembrane,
  			Repeat, Leucine-rich repeat,
  			Glycoprotein
  Contig421_RC	KIAA1821	rab11-family	Hypothetical protein	1073	5041
  		interactingprotein 4
  Contig42256_RC		Transcribed		1074	5042
  		sequences
  Contig42263_RC	PSMB5	ATP synthase, H+	Hydrogen ion transport, CF(0),	1075	5043
  		transporting,	Mitochondrion, Transit peptide,
  		mitochondrial F0	Hypothetical protein
  		complex, subunit s
  		(factor B)
  Contig42270_RC		similar to metallo-	Hypothetical protein	1076	5044
  		beta-lactamase
  		superfamily protein
  Contig42330_RC		Transcribed		1077	5045
  		sequences
  Contig42342_RC		CDNA FLJ39417 fis,	Hypothetical protein	1078	5046
  		clone
  		PLACE6016942
  Contig42418_RC		Transcribed		1079	5047
  		sequence with weak
  		similarity to protein
  		ref: NP_060265.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20378 [Homo
  		sapiens]
  Contig42437_RC	C1orf28	casein kinase 1,	Transferase, Serine/threonine-	1080	5048
  		epsilon	protein kinase, ATP-binding,
  			Phosphorylation, Multigene family
  Contig42459_RC	FLJ22021	hypothetical protein	Repeat, WD repeat	1081	5049
  		FLJ22021
  Contig42566_RC	FLJ14761	hypothetical protein	Hypothetical protein	1082	5050
  		FLJ14761
  Contig42591_RC		shadow of prion		1083	5051
  		protein
  Contig42593_RC		Transcribed		1084	5052
  		sequences
  Contig42597_RC		wd88a09.x1		1085	5053
  		NCI_CGAP_Lu24
  		Homo sapienscDNA
  		clone
  		IMAGE: 2338648 3′,
  		mRNA sequence.
  Contig42615_RC	AMID	apoptosis-inducing	Hypothetical protein	1086	5054
  		factor (AIF)-
  		homologous
  		mitochondrion-
  		associated inducer
  		of death
  Contig42617_RC	SNRPG	Human S6 H-8	Ubiquitin conjugation, Hydrolase,	1087	5055
  		mRNA expressed in	Thiol protease, Multigene family,
  		chromosome 6-	Alternative splicing
  		suppressed
  		melanoma cells.
  Contig42666_RC		chromosome 10	Hypothetical protein	1088	5056
  		open reading frame
  		47
  Contig42759_RC	BCL11B	B-cell	B-cell, Metal-binding, Zinc, Zinc-	1089	5057
  		CLL/lymphoma 11B	finger
  		(zinc finger protein)
  Contig42787_RC		hypothetical protein	Hypothetical protein	1090	5058
  		MGC5509
  Contig42824_RC	FLJ10785	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	1091	5059
  		protease 40	Thiol protease, Alternative splicing,
  			Polymorphism, Multigene family
  Contig42854		CDNA FLJ33578 fis,		1092	5060
  		clone
  		BRAMY2011639
  Contig42903_RC		Transcribed		1093	5061
  		sequence with
  		strong similarity to
  		protein
  		ref: NP_002745.1
  		(H. sapiens)
  		mitogen-activated
  		protein kinase 13;
  		mitogen-activated
  		protein kinase p38
  		delta; stress-
  		activated protein
  		kianse 4 [Homo
  		sapiens]
  Contig42959_RC		solute carrier family	Hypothetical protein	1094	5062
  		5 (sodium/glucose
  		cotransporter),
  		member 10
  Contig42962_RC		Transcribed		1095	5063
  		sequence with weak
  		similarity to protein
  		pir: S41161
  		(H. sapiens) S41161
  		keratin 9,
  		cytoskeletal - human
  Contig43022_RC		similar to RIKEN		1096	5064
  		cDNA 2610524G09
  Contig43026_RC		hypothetical protein	Hypothetical protein	1097	5065
  		DKFZp762C1112
  Contig43096_RC		Clone		1098	5066
  		IMAGE: 5743799,
  		mRNA
  Contig43169_RC		DEAD (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	1099	5067
  		Asp) box polypeptide	Hypothetical protein
  		51
  Contig43184_RC		yg20d12.s1 Soares		1100	5068
  		infant brain 1NIB
  		Homo sapienscDNA
  		clone IMAGE: 329183′,
  		mRNA sequence.
  Contig43189_RC		Transcribed		1101	5069
  		sequences
  Contig43241_RC	ADCY7	adenylate cyclase 7	Lyase, cAMP biosynthesis,	1102	5070
  			Transmembrane, Glycoprotein,
  			Repeat, Metal-binding, Magnesium
  Contig43253_RC	KIAA1858	zinc finger protein	Transcription regulation, DNA-	1103	5071
  		469	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  Contig43262_RC		Transcribed		1104	5072
  		sequences
  Contig43277_RC		Similar to KIAA1726		1105	5073
  		protein
  		(LOC340554),
  		mRNA
  Contig43289_RC		hypothetical protein		1106	5074
  		LOC170371
  Contig43385_RC	DKFZp762O076	hypothetical protein	Hypothetical protein	1107	5075
  		DKFZp762O076
  Contig43436_RC	FLJ32028	hypothetical protein	Hypothetical protein	1108	5076
  		FLJ32028
  Contig43486_RC	DRB1	developmentally	Hypothetical protein	1109	5077
  		regulated RNA-
  		bindingprotein 1
  Contig43506_RC		GLI pathogenesis-		1110	5078
  		related 1 (glioma)
  Contig43513_RC	TIGD7	Homo sapienscDNA		1111	5079
  		FLJ13533 fis, clone
  		PLACE1006371.
  Contig43534		ankyrin repeat	Hypothetical protein, ANK repeat,	1112	5080
  		domain 10	Repeat
  Contig43540_RC	GRIM19	FLJ44968 protein	Oxidoreductase, Ubiquinone, NAD,	1113	5081
  			Apoptosis, Mitochondrion,
  			Transmembrane, Acetylation,
  			Hypothetical protein
  Contig43542_RC		KIAA1718 protein	Hypothetical protein	1114	5082
  Contig43549_RC	SNX5	Homo sapiens, clone	Hypothetical protein, Transport,	1115	5083
  		MGC: 3411	Protein transport
  		IMAGE: 3629947,
  		mRNA, complete
  		cds.
  Contig43586_RC		hypothetical protein		1116	5084
  		LOC134218
  Contig43645_RC		hypothetical protein	Hypothetical protein	1117	5085
  		LOC129607
  Contig43655_RC	NAG14	leucine rich repeat	Immunoglobulin domain,	1118	5086
  		containing 4	Hypothetical protein, Signal
  Contig43658_RC		likely ortholog of		1119	5087
  		mouse cancer
  		related gene -liver 2
  Contig4365_RC	TGOLN2	trans-golgi network	Hypothetical protein, Signal,	1120	5088
  		protein 2	Transmembrane, Glycoprotein,
  			Repeat, Golgi stack, Alternative
  			splicing
  Contig43673_RC	FLJ20481	calpainsmall subunit 2	Hypothetical protein	1121	5089
  Contig43679_RC	MEF-2	myelin expression	Hypothetical protein	1122	5090
  		factor 2
  Contig43694_RC	TSPAN-2	tetraspan 2	Glycoprotein, Transmembrane	1123	5091
  Contig43703_RC	CDH13	CDNA FLJ25967 fis,	Cell adhesion, Glycoprotein,	1124	5092
  		clone CBR01929	Calcium-binding, Repeat, GPI-
  			anchor, Signal
  Contig43724_RC	FLJ13213	hypothetical protein	Hypothetical protein	1125	5093
  		FLJ13213
  Contig43746_RC		CDNA FLJ41107 fis,		1126	5094
  		clone
  		BLADE2007923
  Contig43749_RC	MGC14258	Rho GTPase	Hypothetical protein	1127	5095
  		activating protein 19
  Contig43750_RC		cleavage and		1128	5096
  		polyadenylation
  		specific factor 6,
  		68 kDa
  Contig43817_RC	RINZF	zinc finger and BTB	Hypothetical protein, Metal-binding,	1129	5097
  		domain containing	Zinc, Zinc-finger
  		10
  Contig438_RC		hypothetical protein	EGF-like domain, Hypothetical	1130	5098
  		MGC61716	protein
  Contig4399_RC	MYH9	myosin, heavy	Myosin, ATP-binding, Calmodulin-	1131	5099
  		polypeptide 9, non-	binding, Actin-binding, Coiled coil,
  		muscle	Multigene family, Disease mutation,
  			Deafness, Hypothetical protein
  Contig440	MGC3165	Homo sapiens, H2A	Acetylation, Chromosomal	1132	5100
  		histone family,	protein, DNA-binding, Multigene
  		member L, clone	family, Nuclear protein, Nucleosome
  		MGC: 3165	core
  		IMAGE: 3355200,
  		mRNA, complete
  		cds.
  Contig44059_RC		hypothetical protein	Hypothetical protein	1133	5101
  		DKFZp564B1162
  Contig44078	TA-WDRP	T-cell activation WD	Hypothetical protein, Repeat, WD	1134	5102
  		repeat protein	repeat
  Contig44105	OSBPL11	oxysterol binding	Hypothetical protein, Lipid transport,	1135	5103
  		protein-like 11	Transport
  Contig44124_RC		CDNA FLJ30906 fis,	Hypothetical protein	1136	5104
  		clone
  		FEBRA2006055
  Contig44133_RC	FLJ11362	hypothetical protein	Hypothetical protein, ANK repeat,	1137	5105
  		FLJ11362	Repeat
  Contig44192_RC		Cas-Br-M (murine)	Hypothetical protein, Ligase, Ubl	1138	5106
  		ecotropic retroviral	conjugation pathway, Proto-
  		transforming	oncogene, Zinc-finger, SH2 domain,
  		sequence	Phosphorylation, Calcium-binding,
  			3D-structure
  Contig44226_RC	TIGD2	tigger transposable		1139	5107
  		element derived 2
  Contig44265_RC		ATPase,	Hydrolase, Transmembrane,	1140	5108
  		aminophospholipid	Phosphorylation, Magnesium, ATP-
  		transporter (APLT),	binding, Alternative splicing,
  		Class I, type 8A,	Multigene family
  		member
  1
  Contig44278_RC	DKFZp434K114	WD repeat domain	Repeat, WD repeat, Hypothetical	1141	5109
  		21	protein, Plasmid
  Contig44343		CDNA FLJ26676 fis,		1142	5110
  		clone MPG03726
  Contig44358_RC	DKFZp434N035	Hypothetical	Hypothetical protein	1143	5111
  		LOC284874
  		(LOC284874),
  		mRNA
  Contig44409		similar to LL5 beta	Hypothetical protein	1144	5112
  Contig44414_RC	SLC30A1	solute carrier family	Zinc transport, Transport,	1145	5113
  		30 (zinc transporter),	Transmembrane,Multigene family
  		member
  1
  Contig44492_RC		Transcribed		1146	5114
  		sequences
  Contig44518_RC	FAM11A	family with sequence	Antigen, Multigene family, Tumor	1147	5115
  		similarity 11,	antigen, Hypothetical protein
  		member A
  Contig44521_RC		LSM8 homolog, U6	Nuclear protein, Ribonucleoprotein,	1148	5116
  		small nuclear RNA	mRNA splicing, mRNA processing,
  		associated (S. cerevisiae)	RNA-binding, Acetylation
  Contig44548_RC		hypothetical protein		1149	5117
  		LOC283508
  Contig44593_RC		retinoblastoma	Hypothetical protein, Metal-binding,	1150	5118
  		binding protein 6	Zinc, Zinc-finger
  Contig44595_RC		hypothetical protein	Hypothetical protein	1151	5119
  		MGC45840
  Contig44596_RC	PPIL3	peptidylprolyl	Isomerase, Rotamase, Hypothetical	1152	5120
  		isomerase	protein
  		(cyclophilin)-like 3
  Contig44708_RC	BCAT1	Homo sapiens	Hypothetical protein, Transferase,	1153	5121
  		cDNA: FLJ21270 fis,	Aminotransferase, Branched-chain
  		clone COL01749.	amino acid biosynthesis, Pyridoxal
  			phosphate
  Contig44713		transducin-like	Transcription regulation, Repressor,	1154	5122
  		enhancer of split 4	Nuclear protein, Repeat, WD repeat,
  		(E(sp1) homolog,	Phosphorylation, Wnt signaling
  		Drosophila)	pathway
  Contig44720_RC	FKSG32	hypothetical protein	Hypothetical protein	1155	5123
  		FKSG32
  Contig44723_RC		Human cAMP-		1156	5124
  		binding guanine
  		nucleotide exchange
  		factor IV (cAMP-
  		GEFIV) mRNA,
  		clone W15, partial
  		sequence
  Contig44757_RC	VIM	Transcribed	Hypothetical protein, Coiled coil,	1157	5125
  		sequence with	Intermediate filament,
  		strong similarity to	Phosphorylation, 3D-structure
  		protein pir: A25074
  		(H. sapiens) A25074
  		vimentin - human
  Contig44817_RC	C20orf147	chromosome	20	Hydrolase	1158	5126
  		open reading frame
  		147
  Contig44874_RC	LOC57805	p30 DBC protein	Hypothetical protein	1159	5127
  Contig44877_RC	KIAA1877	beta-galactoside	Hypothetical protein, Transferase,	1160	5128
  		alpha-2,6-	Glycosyltransferase
  		sialyltransferase II
  Contig44964_RC		hypothetical gene		1161	5129
  		supported by
  		BC017510;
  		BC046919
  Contig45004_RC		hypothetical protein		1162	5130
  		LOC283129
  Contig45080_RC	CUL5	cullin	5	Ubl conjugation pathway, Ubl	1163	5131
  			conjugation, Receptor
  Contig45085_RC	ATP6V0A2	Homo sapienscDNA	Hydrogen ion transport,	1164	5132
  		FLJ32238 fis, clone	Transmembrane, Glycoprotein,
  		PLACE6004993.	Hypothetical protein
  Contig45135		CDNA: FLJ22382		1165	5133
  		fis, clone HRC07514
  Contig45201_RC	C1QTNF2	C1q and tumor	Collagen, Signal	1166	5134
  		necrosis factor
  		related protein 2
  Contig45290_RC		Similar to RIKEN		1167	5135
  		cDNA 3010021M21
  		(LOC388185),
  		mRNA
  Contig45304_RC	DEPC-1	prostate cancer		1168	5136
  		antigen-1
  Contig45305_RC	MGC3130	hypothetical protein	Hypothetical protein	1169	5137
  		MGC3130
  Contig45328_RC		Similar to Ab2-183		1170	5138
  		(LOC158830),
  		mRNA
  Contig45338_RC	CSNK2A1	casein kinase 2,	Transferase, Serine/threonine-	1171	5139
  		alpha 1 polypeptide	protein kinase, ATP-binding, Wnt
  			signaling pathway, 3D-structure
  Contig45377_RC	C10orf2	progressive external	Hypothetical protein, Helicase	1172	5140
  		ophthalmoplegia 1
  Contig45381_RC		hypothetical protein		1173	5141
  		LOC283663
  Contig45396_RC	FLJ13197	hypothetical protein	Hypothetical protein	1174	5142
  		FLJ13197
  Contig45397_RC	FLJ34299	zinc finger protein 92	Hypothetical protein, Metal-binding,	1175	5143
  		(HTF12)	Nuclear protein, Zinc, Zinc-finger,
  			Transcription regulation, DNA-
  			binding, Repeat
  Contig45437		similar to RNA	Hypothetical protein	1176	5144
  		polymeraseB
  		transcription factor
  3
  Contig45440_RC		Similar to RIKEN		1177	5145
  		cDNA 9330196J05
  		(LOC340075),
  		mRNA
  Contig45455_RC		soluble liver		1178	5146
  		antigen/liver
  		pancreas antigen
  Contig45457_RC	CYP4F12	cytochrome P450,	Oxidoreductase, Monooxygenase,	1179	5147
  		family 4, subfamily	Electron transport, Membrane,
  		F,polypeptide 12	Heme, Microsome, Endoplasmic
  			reticulum, Polymorphism
  Contig45540_RC		G protein-coupled	Receptor	1180	5148
  		receptor 114
  Contig45544_RC		protein kinase,	Hypothetical protein, Kinase	1181	5149
  		interferon-inducible
  		double stranded
  		RNA dependent
  		activator
  Contig45569_RC	CDC14B	CDC14 cell division	Hydrolase	1182	5150
  		cycle 14 homolog B
  		(S. cerevisiae)
  Contig45624_RC	HAKAI	Cas-Br-M (murine)	Hypothetical protein, Metal-binding,	1183	5151
  		ecotropic retroviral	Zinc, Zinc-finger
  		transforming
  		sequence-like 1
  Contig45634_RC		Similar to FLJ46354	Hypothetical protein	1184	5152
  		protein
  		(LOC389694),
  		mRNA
  Contig45642_RC		mitogen-activated	ATP-binding, Kinase, Transferase,	1185	5153
  		protein kinase	Serine/threonine-protein kinase,
  		kinase kinase 2	Hypothetical protein
  Contig45790_RC	KIAA0187	ESTs, Moderately		1186	5154
  		similar to KIAA0187
  		gene product [Homo
  		sapiens] [H. sapiens]
  Contig45800_RC	MTX1	metaxin 1	Mitochondrion, Outer membrane,	1187	5155
  			Transmembrane, Transport, Protein
  			transport
  Contig45816_RC	MGC4832	chromosome 13	Hypothetical protein	1188	5156
  		open reading frame 3
  Contig45821_RC	ADCY4	adenylate cyclase 4	Hypothetical protein, Lyase, cAMP	1189	5157
  			biosynthesis, Transmembrane,
  			Glycoprotein, Repeat, Metal-binding,
  			Magnesium
  Contig45847_RC	DKFZP761I2123	hypothetical protein	Hypothetical protein	1190	5158
  		DKFZp761I2123
  Contig45879_RC	KIAA1145	KIAA1145 protein	Hypothetical protein,	1191	5159
  			Transmembrane
  Contig45891_RC		CDNA FLJ37509 fis,		1192	5160
  		clone
  		BRCAN1000065
  Contig45944_RC	ZNF335	zinc finger protein	Transcription regulation, Zinc-finger,	1193	5161
  		335	Metal-binding, Nuclear protein, DNA-
  			binding, Repeat
  Contig45945_RC		Transcribed		1194	5162
  		sequences
  Contig4595		hypothetical	Hypothetical protein	1195	5163
  		LOC387763
  Contig45975_RC		Transcribed		1196	5164
  		sequences
  Contig45984	USP7	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	1197	5165
  		protease 7 (herpes	Thiol protease, Multigene family,
  		virus-associated)	Nuclear protein, 3D-structure
  Contig46052_RC		ectonucleoside	Hydrolase, Transmembrane,	1198	5166
  		triphosphate	Antigen, Glycoprotein, Calcium,
  		diphosphohydrolase 1	Magnesium, Alternative splicing,
  			Lipoprotein, Palmitate
  Contig46178_RC		Homo sapiens, clone		1199	5167
  		IMAGE: 5276307,
  		mRNA.
  Contig461_RC	KIAA1836	KIAA1836 protein	Hypothetical protein	1200	5168
  Contig46202	MAD	MAX dimerization	Nuclear protein, DNA-binding,	1201	5169
  		protein 1	Transcription regulation, Repressor,
  			3D-structure
  Contig46218_RC		Similar to		1202	5170
  		diaphanous homolog
  		3 (Drosophila), clone
  		IMAGE: 5277415,
  		mRNA
  Contig46244_RC		Clone		1203	5171
  		IMAGE: 111705
  		mRNA sequence
  Contig46262_RC		Similar to		1204	5172
  		2010300C02Rik
  		protein
  		(LOC343990),
  		mRNA
  Contig46265_RC		LOH11CR1J gene,		1205	5173
  		loss of
  		heterozygosity, 11,
  		chromosomal region
  		1 gene J product
  Contig46294_RC		Transcribed		1206	5174
  		sequence with weak
  		similarity to protein
  		ref: NP_060312.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20489 [Homo
  		sapiens]
  Contig46306_RC		CDNA FLJ36097 fis,		1207	5175
  		clone
  		TESTI2020956
  Contig46343_RC	SPP1	suppressor of	SH2 domain, Growth regulation,	1208	5176
  		cytokine signaling 7	Signal transduction inhibitor
  Contig46375_RC		CDNA FLJ26349 fis,		1209	5177
  		clone HRT04618
  Contig46376_RC		zinc finger and BTB	Hypothetical protein, Metal-binding,	1210	5178
  		domain containing	Zinc, Zinc-finger
  		10
  Contig46399_RC		Transcribed		1211	5179
  		sequences
  Contig46416_RC	MGC33212	hypothetical protein		1212	5180
  		MGC33212
  Contig46421_RC		Transcribed		1213	5181
  		sequence with
  		moderate similarity
  		to protein
  		ref: NP_005496.1
  		(H. sapiens) CD36
  		antigen
  Contig46437_RC		synaptotagmin	Transport, Protein transport	1214	5182
  		binding, cytoplasmic
  		RNA interacting
  		protein
  Contig46443_RC		solute carrier family	Hypothetical protein	1215	5183
  		26, member 11
  Contig46464_RC		Transcribed		1216	5184
  		sequences
  Contig46482_RC		MRNA; cDNA		1217	5185
  		DKFZp434C1435
  		(from clone
  		DKFZp434C1435)
  Contig46506_RC		MRNA; cDNA		1218	5186
  		DKFZp686C18110
  		(from clone
  		DKFZp686C18110)
  Contig46536_RC	LGI3	leucine-rich repeat	Repeat, Leucine-rich repeat, Signal,	1219	5187
  		LGI family, member 3	Hypothetical protein
  Contig46563_RC		Transcribed		1220	5188
  		sequences
  Contig46567		Transcribed		1221	5189
  		sequences
  Contig46586	UBE2D3	ubiquitin-conjugating	Hypothetical protein, Ligase, Ubl	1222	5190
  		enzyme E2D 3	conjugation pathway, Multigene
  		(UBC4/5 homolog,	family
  		yeast)
  Contig46590	RAD50	CDNA FLJ46914 fis,	Hypothetical protein	1223	5191
  		clone
  		SPLEN2027852
  Contig46591_RC		hypothetical protein		1224	5192
  		LOC90639
  Contig46601_RC		CDNA FLJ42198 fis,		1225	5193
  		clone
  		THYMU2034338
  Contig46602_RC		zinc finger, CCHC	Hypothetical protein	1226	5194
  		domain containing 6
  Contig46634		Transcribed		1227	5195
  		sequences
  Contig46700_RC	LSP1	small proline rich	Phosphorylation, T-cell	1228	5196
  		protein 4
  Contig46709_RC	FLJ23045	chromosome 20	Transport, Protein transport,	1229	5197
  		open reading frame	Hypothetical protein
  		23
  Contig46732_RC		zinc finger protein	Hypothetical protein, Zinc-finger,	1230	5198
  		207	Metal-binding, DNA-binding, Nuclear
  			protein, Alternative splicing
  Contig46747_RC		parvin, gamma	Cell adhesion, Cytoskeleton, Actin-	1231	5199
  			binding, Repeat, Alternative splicing
  Contig46860_RC		FLJ20758 protein	Hypothetical protein	1232	5200
  Contig46881_RC		Transcribed		1233	5201
  		sequences
  Contig46954_RC	PNMA3	paraneoplastic	Hypothetical protein	1234	5202
  		antigen MA3
  Contig46999_RC		CDNA FLJ26950 fis,		1235	5203
  		clone RCT08544
  Contig47014_RC	MGC24180	hypothetical protein	Hypothetical protein	1236	5204
  		MGC24180
  Contig47015_RC		hypothetical protein	Hypothetical protein	1237	5205
  		FLJ21439
  Contig47025_RC		Hypothetical gene		1238	5206
  		supported by
  		AK094796
  		(LOC400764),
  		mRNA
  Contig47042	FLJ20069	Abelson helper	Hypothetical protein, Repeat, SH3	1239	5207
  		integration site	domain, WD repeat
  Contig47081_RC		LOC392751		1240	5208
  		(LOC392751),
  		mRNA
  Contig47096_RC	PFKFB4	6-phosphofructo-2-	Multifunctional enzyme, Transferase,	1241	5209
  		kinase/fructose-2,6-	Kinase, Hydrolase, ATP-binding,
  		biphosphatase 4	Phosphorylation, Multigene family,
  			3D-structure
  Contig47184_RC		LOC400813		1242	5210
  		(LOC400813),
  		mRNA
  Contig47203_RC		sortilin-related	Endocytosis, Receptor,	1243	5211
  		receptor, L(DLR	Transmembrane, EGF-like domain,
  		class) A repeats-	Repeat, Glycoprotein, LDL, Lipid
  		containing	transport, Cholesterol metabolism,
  			Signal
  Contig47221_RC	VCP	valosin-containing	ATP-binding, Transport,	1244	5212
  		protein	Phosphorylation, Repeat, Golgi
  			stack, Endoplasmic reticulum,
  			Hypothetical protein
  Contig47368_RC	LOC92691	hypothetical protein	Hypothetical protein	1245	5213
  		BC008604
  Contig47441_RC		ubiquitin-conjugating	Ligase, Ubl conjugation pathway,	1246	5214
  		enzyme E2 variant 2	Vitamin D
  Contig47464_RC	ZNF335	zinc finger protein	Transcription regulation, Zinc-finger,	1247	5215
  		335	Metal-binding, Nuclear protein, DNA-
  			binding, Repeat
  Contig47495_RC	IDI2	GTP binding protein 4	GTP-binding, Nuclear protein	1248	5216
  Contig47498_RC	TMPRSS5	transmembrane	Hydrolase, Serine protease,	1249	5217
  		protease, serine 5	Transmembrane, Signal-anchor,
  		(spinesin)	Glycoprotein
  Contig47539_RC		SGT1, suppressor of	Ubl conjugation pathway, Repeat,	1250	5218
  		G2 allele of SKP1	TPR repeat
  		(S. cerevisiae)
  Contig47582_RC	FLJ22757	family with sequence	Hypothetical protein	1251	5219
  		similarity 31,
  		member C
  Contig47732_RC	EPS8R3	EPS8-like 3	SH3 domain, Hypothetical protein,	1252	5220
  			Receptor
  Contig47770_RC	LY6G6C	lymphocyte antigen	Signal	1253	5221
  		6 complex, locus
  		G6C
  Contig47793_RC	FLJ23311	FLJ23311 protein	Hypothetical protein	1254	5222
  Contig47801_RC		CDNA FLJ45814 fis,		1255	5223
  		clone
  		NT2RP7018126
  Contig47810_RC	IMMP2L	IMP2 inner	Coated pits	1256	5224
  		mitochondrial
  		membrane protease-
  		like (S. cerevisiae)
  Contig47814_RC	HHGP	phosphoribosyl	Transferase	1257	5225
  		transferase domain
  		containing 1
  Contig47835_RC		similar to RIKEN	Hypothetical protein	1258	5226
  		cDNA 2600017H02
  Contig47863_RC	FLJ11939	latrophilin 1	Hypothetical protein, Receptor,	1259	5227
  			Transmembrane
  Contig47889_RC	COPS7B	COP9 constitutive	Hypothetical protein	1260	5228
  		photomorphogenic
  		homolog subunit 7B
  		(Arabidopsis)
  Contig47900_RC	FLJ12604	hypothetical protein	Hypothetical protein	1261	5229
  		FLJ12604
  Contig47912_RC	NR1D2	nuclear receptor	Hypothetical protein, Receptor,	1262	5230
  		subfamily 1, group	Transcription regulation, DNA-
  		D, member 2	binding, Nuclear protein, Zinc-finger,
  			Repressor
  Contig47922_RC	BRAP	BRCA1 associated	Metal-binding, Zinc, Zinc-finger	1263	5231
  		protein
  Contig47926_RC	FLJ13057	germ cell-less	Hypothetical protein	1264	5232
  		homolog 1
  		(Drosophila)
  Contig47942_RC	LOC91893	hypothetical protein	Hypothetical protein	1265	5233
  		BC006136
  Contig47975_RC		CDNA clone		1266	5234
  		IMAGE: 5757380,
  		partial cds
  Contig47982_RC		hypothetical protein		1267	5235
  		LOC112868
  Contig48059	FLJ12788	hypothetical protein	Hypothetical protein	1268	5236
  		FLJ12788
  Contig48144_RC	FLJ11152	chromosome 6 open	Hypothetical protein	1269	5237
  		reading frame 70
  Contig48156_RC		proprotein	Cholesterol metabolism, Lipid	1270	5238
  		convertase	metabolism, Hydrolase, Protease,
  		subtilisin/kexin type 9	Serine protease, Calcium, Signal,
  			Autocatalytic cleavage, Zymogen,
  			Glycoprotein, Alternative splicing,
  			Polymorphism, Disease mutation
  Contig48168_RC	LOC113246	CDNA FLJ46484 fis,	Hypothetical protein	1271	5239
  		clone
  		THYMU3026350
  Contig48215_RC	FLJ35801	hypothetical protein	Hypothetical protein	1272	5240
  		FLJ35801
  Contig48249_RC	FLJ10849	hypothetical protein	Hypothetical protein	1273	5241
  		FLJ10849
  Contig48270_RC	LOC144097	hypothetical protein	Hypothetical protein	1274	5242
  		BC007540
  Contig48277_RC	FLJ36175	hypothetical protein	Repeat, WD repeat, Hypothetical	1275	5243
  		FLJ36175	protein
  Contig48290_RC	MN7	CDNA FLJ43285 fis,	Hypothetical protein	1276	5244
  		clone
  		MESAN2000067
  Contig48355_RC		methionine		1277	5245
  		aminopeptidase 1D
  Contig48371		malate	Oxidoreductase, Tricarboxylic acid	1278	5246
  		dehydrogenase 1,	cycle, NAD
  		NAD (soluble)
  Contig48406_RC		chromosome 12	Hypothetical protein	1279	5247
  		open reading frame 6
  Contig48466_RC	FLJ12649	hypothetical protein	Hypothetical protein	1280	5248
  		FLJ12649
  Contig48472_RC	MAD3	MAX dimerization	Hypothetical protein	1281	5249
  		protein 3
  Contig48480_RC		ring finger protein 24	Zinc-finger	1282	5250
  Contig48489_RC		similar to	Hypothetical protein	1283	5251
  		K06A9.1b.p
  Contig48506_RC	KIAA1799	KIAA1799 protein	Hypothetical protein	1284	5252
  Contig48529_RC	CKLFSF2	chemokine-like	Chemotaxis, Cytokine,	1285	5253
  		factor super family 2	Transmembrane
  Contig48588_RC	KIAA1706	KIAA1706 protein	Hypothetical protein	1286	5254
  Contig48697_RC	PFKFB2	6-phosphofructo-2-	Multifunctional enzyme, Transferase,	1287	5255
  		kinase/fructose-2,6-	Kinase, Hydrolase, ATP-binding,
  		biphosphatase 2	Phosphorylation, Alternative splicing,
  			Multigene family
  Contig48722_RC		Clone		1288	5256
  		IMAGE: 5729395,
  		mRNA
  Contig48764_RC		CDNA clone	Hypothetical protein	1289	5257
  		MGC: 71984
  		IMAGE: 4280819,
  		complete cds
  Contig48806_RC		Similar to RIKEN		1290	5258
  		cDNA E130012A19
  		(LOC390789),
  		mRNA
  Contig48830_RC	RPL13	ribosomal protein	Ribosomal protein	1291	5259
  		L13
  Contig48834_RC	YR-29	KIAA0888 protein	Nuclear protein	1292	5260
  Contig48914_RC		hypothetical protein	Hypothetical protein	1293	5261
  		MGC24133
  Contig48944_RC		Transcribed		1294	5262
  		sequences
  Contig48951_RC		chromosome 9 open	Hypothetical protein	1295	5263
  		reading frame 85
  Contig48983_RC		CDNA FLJ14294 fis,		1296	5264
  		clone
  		PLACE1008181
  Contig48988_RC	LOC51099	abhydrolase domain	Hypothetical protein	1297	5265
  		containing 5
  Contig49000_RC		CDNA FLJ30257 fis,		1298	5266
  		clone
  		BRACE2002467
  Contig49012_RC		hypothetical protein	Hypothetical protein	1299	5267
  		DKFZp434J0617
  Contig49063_RC	A1BG	alpha-1-B	Hypothetical protein,	1300	5268
  		glycoprotein	Immunoglobulin domain,
  			Glycoprotein, Plasma, Repeat,
  			Signal
  Contig49169_RC	SUV39H2	suppressor of	Hypothetical protein, Transferase,	1301	5269
  		variegation 3-9	Methyltransferase, Chromatin
  		homolog 2	regulator, Nuclear protein,
  		(Drosophila)	Alternative splicing
  Contig49185_RC	MGC2744	hypothetical protein	Hypothetical protein	1302	5270
  		MGC2744
  Contig49233_RC	NRBF-2	nuclear receptor	Receptor, Hypothetical protein	1303	5271
  		binding factor 2
  Contig49254_RC	RAD53	Homo sapiens, clone	Hypothetical protein, ATP-binding,	1304	5272
  		MGC: 2637	Kinase, Serine/threonine-protein
  		IMAGE: 3505128,	kinase, Transferase, Cell cycle,
  		mRNA, complete	Phosphorylation, Nuclear protein,
  		cds.	Disease mutation, Li-Fraumeni
  			syndrome, 3D-structure
  Contig49255_RC		leucine-rich PPR-	Hypothetical protein, Repeat	1305	5273
  		motif containing
  Contig49279_RC		hypothetical protein	Hypothetical protein	1306	5274
  		FLJ25461
  Contig49306_RC	DKFZP586K0717	ligand of numb-	Zinc-finger, Repeat, Alternative	1307	5275
  		protein X	splicing
  Contig49344	FLJ22474	growth hormone	Hypothetical protein	1308	5276
  		regulatedTBC
  		protein
  1
  Contig49353_RC	MGC41917	zinc finger protein	Hypothetical protein, Metal-binding,	1309	5277
  		550	Nuclear protein, Zinc, Zinc-finger
  Contig49409		ty82g05.x1		1310	5278
  		NCI_CGAP_Kid11
  		Homo sapienscDNA
  		clone
  		IMAGE: 2285624 3′,
  		mRNA sequence.
  Contig49468_RC		MRNA; cDNA		1311	5279
  		DKFZp667N1113
  		(from clone
  		DKFZp667N1113)
  Contig49509_RC	KIAA1673	cytoplasmic	Hypothetical protein	1312	5280
  		polyadenylation
  		elementbinding
  		protein
  4
  Contig49522_RC		hypothetical protein	Hypothetical protein	1313	5281
  		FLJ13105
  Contig49578_RC	FLJ20274	xj92d05.x1	Hypothetical protein	1314	5282
  		Soares_NFL_T_GBC_S1
  		Homo sapiens
  		cDNA clone
  		IMAGE: 2664681 3′,
  		mRNA sequence.
  Contig49591_RC		activating	Hypothetical protein	1315	5283
  		transcription factor 7
  		interactingprotein 2
  Contig49631_RC	ATP11C	ATPase, Class VI,	Hydrolase, Transmembrane,	1316	5284
  		type 11C	Phosphorylation, Magnesium, Metal-
  			binding, ATP-binding, Multigene
  			family, Alternative splicing
  Contig49667_RC		deaminase domain		1317	5285
  		containing 1
  Contig49673_RC	AD034	RIO kinase 1 (yeast)	Kinase, Hypothetical protein	1318	5286
  Contig49725_RC	LOC51611	CDNA clone	Transferase, Methyltransferase,	1319	5287
  		IMAGE: 4821863,	Alternative splicing, Hypothetical
  		partial cds	protein
  Contig49738_RC	ATIC	aj25f09.s1	Purine biosynthesis, Transferase,	1320	5288
  		Soares_testis_NHT	Hydrolase, Multifunctional enzyme
  		Homo sapienscDNA
  		clone 1391369 3′,
  		mRNA sequence.
  Contig49744_RC	FLJ14166	hypothetical protein	Hypothetical protein	1321	5289
  		FLJ14166
  Contig49756_RC		Transcribed		1322	5290
  		sequences
  Contig49849_RC	C6orf1	hypothetical protein	Hypothetical protein	1323	5291
  		MGC57858
  Contig49855	MGC33338	hypothetical protein	Hypothetical protein	1324	5292
  		MGC33338
  Contig49875		Full length insert		1325	5293
  		cDNA YN61C04
  Contig49948_RC	MGC27385	potassium channel	Hypothetical protein	1326	5294
  		tetramerisation
  		domain containing 6
  Contig49966_RC		CDNA FLJ31683 fis,		1327	5295
  		clone
  		NT2RI2005353
  Contig49983_RC	MGC3121	hypothetical protein	Hypothetical protein	1328	5296
  		MGC3121
  Contig49991_RC		Transcribed		1329	5297
  		sequence with weak
  		similarity to protein
  		ref: NP_062553.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ11267 [Homo
  		sapiens]
  Contig50039_RC	KIAA0140	similar to CG9643-	Hypothetical protein	1330	5298
  		PA
  Contig50106_RC	KIAA1708	kinesin family	Hypothetical protein	1331	5299
  		member 21A
  Contig50117_RC		Transcribed		1332	5300
  		sequences
  Contig50134_RC	BITE	p10-binding protein	Hypothetical protein	1333	5301
  Contig50137_RC	MGC12992	hypothetical protein	GTP-binding, Microtubules, Multigene	1334	5302
  		MGC12992	family
  Contig50177_RC	MBLR	ring finger protein	Hypothetical protein, Metal-binding,	1335	5303
  		134	Zinc, Zinc-finger
  Contig50190_RC	LOC51005	MRNA; cDNA	Glycoprotein, Ion transport, Ionic	1336	5304
  		DKFZp313E2215	channel, Transmembrane
  		(from clone
  		DKFZp313E2215)
  Contig50194_RC	C9orf16	chromosome 9 open	Hypothetical protein, Coiled coil	1337	5305
  		reading frame 16
  Contig50211_RC	MGC35392	hypothetical protein	Hypothetical protein	1338	5306
  		MGC35392
  Contig50220_RC	FLJ13231	hypothetical protein	Hypothetical protein	1339	5307
  		FLJ13231
  Contig50232_RC	DDX31	DEAD (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	1340	5308
  		Asp) box polypeptide	Hypothetical protein
  		31
  Contig50249_RC	MGC23908	similar to RNA	Hypothetical protein	1341	5309
  		polymeraseB
  		transcription factor
  3
  Contig50272_RC		Transcribed		1342	5310
  		sequences
  Contig50273_RC		hypothetical protein	Hypothetical protein	1343	5311
  		LOC255783
  Contig50275_RC	gm117	gm117		1344	5312
  Contig50293_RC	EGFR-RS	rhomboid family	1	Hypothetical protein, Receptor	1345	5313
  		(Drosophila)
  Contig50295_RC	FLJ12541	stimulated by	Hypothetical protein	1346	5314
  		retinoic acid gene 6
  Contig50298_RC	FLJ32370	hypothetical protein	Hypothetical protein	1347	5315
  		FLJ32370
  Contig50324_RC	LOC51044	CDNA FLJ25011 fis,		1348	5316
  		clone CBL01244
  Contig50337_RC	MGC4645	hypothetical protein	Hypothetical protein, Repeat, WD	1349	5317
  		MGC4645	repeat
  Contig50381_RC	CD109	CD109 antigen (Gov	Hypothetical protein	1350	5318
  		platelet alloantigens)
  Contig50391_RC		Transcribed		1351	5319
  		sequence with
  		moderate similarity
  		to protein
  		ref: NP_060312.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20489 [Homo
  		sapiens]
  Contig50436_RC		CDNA FLJ37094 fis,		1352	5320
  		clone
  		BRACE2018337
  Contig50465_RC		Transcribed		1353	5321
  		sequences
  Contig50483	KIAA1718	KIAA1718 protein	Hypothetical protein	1354	5322
  Contig50490_RC	LOC90678	leucine rich repeat	Hypothetical protein	1355	5323
  		and sterile alpha
  		motif containing 1
  Contig50501_RC		coronin, actin	Actin-binding, Repeat, WD repeat,	1356	5324
  		binding protein, 2A	Coiled coil
  Contig50595_RC		hypothetical protein	Hypothetical protein	1357	5325
  		LOC147111
  Contig50605_RC		wj49g02.x1		1358	5326
  		NCI_CGAP_Lu19
  		Homo sapienscDNA
  		clone
  		IMAGE: 2406194 3′,
  		mRNA sequence.
  Contig50669_RC	KIF9	kinesin family	Hypothetical protein, Motor protein,	1359	5327
  		member 9	Microtubule, ATP-binding, Coiled
  			coil, Alternative splicing
  Contig50675	BA108L7.2	similar to rat	Hypothetical protein, Transport, Iron	1360	5328
  		tricarboxylate	transport, Mitochondrion,
  		carrier-like protein	Transmembrane
  Contig50687_RC	MINA53	hypothetical protein	Hypothetical protein	1361	5329
  		DKFZp667G2110
  Contig506_RC	KIAA1821	rab11-family	Hypothetical protein	1362	5330
  		interactingprotein 4
  Contig50728_RC		Transcribed		1363	5331
  		sequence with weak
  		similarity to protein
  		ref: NP_071385.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20958 [Homo
  		sapiens]
  Contig50747_RC	MGC23427	BTB (POZ) domain		1364	5332
  		containing 14A
  Contig50759	DKFZp761P1121	hypothetical protein	Hypothetical protein, RNA-binding,	1365	5333
  		DKFZp761P1121	Repeat, Alternative splicing
  Contig50787_RC	FLJ31528	hypothetical protein	Hypothetical protein	1366	5334
  		FLJ31528
  Contig50814_RC	MGC27027	immune associated	Hypothetical protein	1367	5335
  		nucleotide
  Contig50831_RC		LOC389865		1368	5336
  		(LOC389865),
  		mRNA
  Contig50838_RC	LOC120224	hypothetical protein	Hypothetical protein	1369	5337
  		BC016153
  Contig50846_RC		zinc finger CCCH	Hypothetical protein	1370	5338
  		type domain
  		containing 5
  Contig50848_RC	KIAA1705	DDHD domain	Lipid degradation, Hydrolase,	1371	5339
  		containing 1	Alternative splicing
  Contig50891_RC		Homo sapiens,	ATP-binding, Kinase,	1372	5340
  		p21/Cdc42/Rac1-	Serine/threonine-protein kinase,
  		activatedkinase 1	Transferase, Apoptosis,
  		(STE20 homolog,	Phosphorylation, 3D-structure
  		yeast), clone
  		MGC: 51883
  		IMAGE: 5763796,
  		mRNA, complete
  		cds.
  Contig50905_RC		CDNA FLJ42250 fis,		1373	5341
  		clone
  		TKIDN2007828
  Contig50920_RC	KIAA1847	Homo sapiens	Hypothetical protein, Zinc-finger,	1374	5342
  		mRNA for KIAA1847	Alternative splicing
  		protein, partial cds.
  Contig51020_RC	MGC21874	transcriptional	Hypothetical protein	1375	5343
  		adaptor 2 (ADA2
  		homolog, yeast)-
  		beta
  Contig51026_RC	DKFZp762A2013	quiescin Q6-like 1	Hypothetical protein, Signal	1376	5344
  Contig51068_RC		CDNA clone		1377	5345
  		IMAGE: 5286843,
  		partial cds
  Contig51070_RC	FLJ25005	FLJ25005 protein	Hypothetical protein	1378	5346
  Contig51087_RC	NPEPL1	aminopeptidase-like 1	Hydrolase, Aminopeptidase, Zinc,	1379	5347
  			Manganese, Alternative splicing
  Contig51103_RC	JFC1	NADPH oxidase-	Hypothetical protein, Repeat,	1380	5348
  		related, C2 domain-	Alternative splicing
  		containing protein
  Contig51105_RC		Transcribed		1381	5349
  		sequence with weak
  		similarity to protein
  		ref: NP_062553.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ11267 [Homo
  		sapiens]
  Contig51128_RC	MGC35182	hypothetical protein	Hypothetical protein	1382	5350
  		MGC35182
  Contig51151_RC	ASP	AKAP-associated		1383	5351
  		sperm protein
  Contig51163_RC		hypothetical protein	Hypothetical protein	1384	5352
  		MGC45871
  Contig51170_RC		bruno-like 4, RNA	Hypothetical protein	1385	5353
  		binding protein
  		(Drosophila)
  Contig51254_RC	CLG	likely ortholog of	Hypothetical protein	1386	5354
  		mouse common-site
  		lymphoma/leukemia
  		GEF
  Contig51288_RC	NR2C2	nuclear receptor	Receptor, Transcription regulation,	1387	5355
  		subfamily 2, group	DNA-binding, Nuclear protein, Zinc-
  		C,member 2	finger
  Contig51291_RC	KIAA1977	KIAA1977 protein	Hypothetical protein, ANK repeat,	1388	5356
  			Repeat
  Contig51297_RC	FLJ33817	hypothetical protein	Hypothetical protein, Repeat, WD	1389	5357
  		FLJ33817	repeat
  Contig51311_RC	KDELC1	KDEL (Lys-Asp-Glu-	Hypothetical protein	1390	5358
  		Leu) containing 1
  Contig51373_RC	KIAA1688	KIAA1688 protein	Repeat	1391	5359
  Contig51414_RC	FLJ23441	hypothetical protein	Hypothetical protein	1392	5360
  		FLJ23441
  Contig51417_RC	SHANK3	SH3 and multiple	SH3-binding, Coiled coil,	1393	5361
  		ankyrin repeat	Chromosomal translocation
  		domains
  3
  Contig51449_RC		RAB15, member	Hypothetical protein, Plasmid	1394	5362
  		RAS onocogene
  		family
  Contig51519_RC		spastic paraplegia 6	Hypothetical protein	1395	5363
  		(autosomal
  		dominant)
  Contig51526_RC	RAB39B	RAB39B, member	GTP-binding, Lipoprotein,	1396	5364
  		RAS oncogene	Prenylation, Transport, Protein
  		family	transport
  Contig51553_RC	MGC3200	hypothetical protein	Hypothetical protein	1397	5365
  		MGC3200
  Contig51567_RC		hypothetical protein	Hypothetical protein	1398	5366
  		MGC33371
  Contig51621_RC		ubiquitin specific	Hypothetical protein, Ubl conjugation	1399	5367
  		protease 13	pathway, Hydrolase, Thiol protease,
  		(isopeptidase T-3)	Multigene family, Repeat
  Contig51625_RC		Clone	Hypothetical protein	1400	5368
  		IMAGE: 3868989,
  		mRNA, partial cds
  Contig51660_RC	IFRG28	28 kD interferon	Transmembrane	1401	5369
  		responsive protein
  Contig51687_RC	KRTDAP	KIPV467		1402	5370
  Contig51723_RC		Splicing factor,		1403	5371
  		arginine/serine-rich,
  		46 kD
  Contig51726_RC	FLJ20739	Transcribed	Hypothetical protein	1404	5372
  		sequence with weak
  		similarity to protein
  		pir: S41161
  		(H. sapiens)S41161
  		keratin
  9,
  		cytoskeletal - human
  Contig51737_RC		CDNA FLJ38931 fis,		1405	5373
  		clone
  		NT2NE2013189
  Contig51740_RC	FLJ33282	amyotrophic lateral	Hypothetical protein	1406	5374
  		sclerosis 2 (juvenile)
  		chromosome region,
  		candidate 4
  Contig51742_RC	RISC	likely homolog of rat	Hydrolase, Carboxypeptidase,	1407	5375
  		and mouse retinoid-	Signal, Glycoprotein, Alternative
  		inducible serine	splicing
  		carboxypeptidase
  Contig51757		lin-7 homolog A (C. elegans)		1408	5376
  Contig51795_RC	TGFBI	CDNA FLJ37830 fis,	Extracellular matrix, Signal, Repeat,	1409	5377
  		clone	Cell adhesion, Disease mutation,
  		BRSSN2009395	Amyloid, Vision
  Contig51800		Transcribed		1410	5378
  		sequence with
  		strong similarity to
  		protein pdb: 1BGM
  		(E. coli) O Chain O,
  		Beta-Galactosidase
  Contig51809_RC	C21orf63	chromosome 21	Signal, Transmembrane, Repeat,	1411	5379
  		open reading frame	Glycoprotein, Lectin, Alternative
  		63	splicing
  Contig51821_RC	TAF4B	TAF4b RNA	Transcription regulation, Nuclear	1412	5380
  		polymerase II, TATA	protein
  		box binding protein
  		(TBP)-associated
  		factor, 105 kDa
  Contig51882_RC	MGC11335	hypothetical protein	Hypothetical protein	1413	5381
  		MGC11335
  Contig51888_RC		pannexin 1	Gap junction, Transmembrane,	1414	5382
  			Polymorphism
  Contig51896_RC	HT021	HT021		1415	5383
  Contig51917_RC	WBSCR14	Full length insert	Transcription regulation, Repressor,	1416	5384
  		cDNA clone	Nuclear protein, DNA-binding,
  		YI46G04	Williams-Beuren syndrome,
  			Alternative splicing
  Contig51929		PAI-1 mRNA-binding	Hypothetical protein	1417	5385
  		protein
  Contig51964_RC	FLJ40629	hypothetical protein	Hypothetical protein	1418	5386
  		FLJ40629
  Contig51967_RC		solute carrier family	Transport, Symport,	1419	5387
  		16 (monocarboxylic	Transmembrane, Multigene family
  		acid transporters),
  		member 6
  Contig51974_RC		Transcribed	Hypothetical protein, Phospholipid	1420	5388
  		sequences	biosynthesis, Transferase,
  			Acyltransferase, Transmembrane
  Contig52062_RC	FLJ31978	hypothetical protein	Hypothetical protein	1421	5389
  		FLJ31978
  Contig52099_RC		CDNA FLJ41881 fis,		1422	5390
  		clone
  		OCBBF2021833
  Contig52186_RC		zinc finger protein 67	Metal-binding, Zinc, Zinc-finger	1423	5391
  		homolog (mouse)
  Contig52199_RC		CDNA FLJ12540 fis,		1424	5392
  		clone
  		NT2RM4000425
  Contig52220_RC		CDNA FLJ25573 fis,		1425	5393
  		clone JTH06531
  Contig52232_RC	DERMO1	twist homolog 2	Differentiation, Developmental	1426	5394
  		(Drosophila)	protein, Nuclear protein, DNA-
  			binding, Repressor, Transcription
  			regulation
  Contig52242_RC		CDNA FLJ12345 fis,	Hypothetical protein	1427	5395
  		clone
  		MAMMA1002294
  Contig52312_RC	TFEB	transcription factor	Transcription regulation, DNA-	1428	5396
  		EB	binding, Nuclear protein, Alternative
  			splicing
  Contig52317_RC		hypothetical protein	Hypothetical protein, Ubiquinone	1429	5397
  		LOC91942
  Contig52320		Full length insert		1430	5398
  		cDNA clone
  		YX81F03
  Contig52336_RC	MGC2488	homolog of yeast	Hypothetical protein	1431	5399
  		Mis12
  Contig52358_RC		Transcribed		1432	5400
  		sequences
  Contig52405_RC	EDG3	endothelial	G-protein coupled receptor,	1433	5401
  		differentiation,	Transmembrane, Glycoprotein
  		sphingolipid G-
  		protein-coupled
  		receptor, 3
  Contig52414_RC	CAMTA1	calmodulin binding	Hypothetical protein, ANK repeat,	1434	5402
  		transcription	Repeat
  		activator 1
  Contig52443		hypothetical protein		1435	5403
  		INM01
  Contig52482_RC	PNPASE	polyribonucleotide	Hypothetical protein, Exonuclease,	1436	5404
  		nucleotidyltransferase 1	Nucleotidyltransferase, Transferase
  Contig52486_RC	PPARAL	CDNA FLJ31089 fis,		1437	5405
  		clone
  		IMR321000092
  Contig52520_RC		MRNA full length		1438	5406
  		insert cDNA clone
  		EUROIMAGE
  		2068962
  Contig52544_RC	MGC17515	hypothetical protein	Hypothetical protein	1439	5407
  		MGC17515
  Contig52553_RC	LOC197336	similar to RIKEN	Hypothetical protein, Repeat, WD	1440	5408
  		cDNA 3230401M21	repeat
  		[Mus musculus]
  Contig52561_RC		Cas-Br-M (murine)	Hypothetical protein, Ligase, Ubl	1441	5409
  		ecotropic retroviral	conjugation pathway, Proto-
  		transforming	oncogene, Zinc-finger, SH2 domain,
  		sequence	Phosphorylation, Calcium-binding,
  			3D-structure
  Contig52565_RC		MAX dimerization	Nuclear protein, DNA-binding,	1442	5410
  		protein 1	Transcription regulation, Repressor,
  			3D-structure
  Contig52570_RC		CDNA FLJ41853 fis,		1443	5411
  		clone
  		NT2RI3004161
  Contig52579_RC		breast cancer		1444	5412
  		membrane protein
  		101
  Contig52609_RC		hypothetical protein	Hypothetical protein	1445	5413
  		FLJ33814
  Contig52623_RC	FLJ12888	chromosome 9 open	Hypothetical protein	1446	5414
  		reading frame 76
  Contig52648_RC	MGC2404	acyl-Coenzyme A	ANK repeat, Repeat	1447	5415
  		binding domain
  		containing 6
  Contig52659_RC		hypothetical protein	Hypothetical protein	1448	5416
  		LOC255104
  Contig52715_RC		Transcribed		1449	5417
  		sequences
  Contig52720_RC	MGC2714	hypothetical protein	Hypothetical protein	1450	5418
  		MGC2714
  Contig52722_RC	MGC3020	hypothetical protein	Hypothetical protein	1451	5419
  		MGC3020
  Contig5274_RC	C21orf91	chromosome 21	Polymorphism	1452	5420
  		open reading frame
  		91
  Contig52777_RC		Transcribed		1453	5421
  		sequence with
  		strong similarity to
  		protein
  		ref: NP_286085.1 (E. coli)
  		beta-D-
  		galactosidase
  		[Escherichia coli
  		O157:H7 EDL933]
  Contig52786_RC	ZNF198	zinc finger protein	Hypothetical protein, Transcription	1454	5422
  		198	regulation, Nuclear protein,
  			Chromosomal translocation, Repeat,
  			Zinc-finger
  Contig52792_RC	MGC3062	phosducin-like 3		1455	5423
  Contig52814_RC		Transcribed		1456	5424
  		sequences
  Contig52891_RC		membrane	Hypothetical protein	1457	5425
  		associated
  		guanylate kinase
  		interacting protein-
  		like 1
  Contig52914_RC	MGC4663	cytochrome P450,	Hypothetical protein	1458	5426
  		family 2, subfamily
  		R,polypeptide 1
  Contig52924_RC	FLJ14827	hypothetical protein	Hypothetical protein	1459	5427
  		FLJ14827
  Contig52932_RC	DKFZP566D1346	hypothetical protein	Hypothetical protein, ANK repeat,	1460	5428
  		DKFZp566D1346	Repeat
  Contig52945_RC	KIAA1946	KIAA1946 protein	Hypothetical protein	1461	5429
  Contig52971_RC	SCAMP5	secretory carrier	Hypothetical protein	1462	5430
  		membrane protein 5
  Contig52993_RC	MAP3K3	mitogen-activated	Hypothetical protein, ATP-binding,	1463	5431
  		protein kinase	Transferase, Serine/threonine-
  		kinase kinase 3	protein kinase
  Contig52994_RC		Transcribed		1464	5432
  		sequence with weak
  		similarity to protein
  		ref: NP_055301.1
  		(H. sapiens)
  		neuronal thread
  		protein [Homo
  		sapiens]
  Contig53047_RC	TTYH1	tweety homolog 1		1465	5433
  		(Drosophila)
  Contig53066_RC	ARL5	ADP-ribosylation	GTP-binding, Multigene family	1466	5434
  		factor-like 5
  Contig53072_RC	KIAA1474	zinc finger protein	Hypothetical protein, Metal-binding,	1467	5435
  		537	Zinc, Zinc-finger
  Contig53080_RC		CDNA FLJ31655 fis,		1468	5436
  		clone
  		NT2RI2004284
  Contig53149_RC	RIN3	Ras and Rab	GTPase activation, SH2 domain,	1469	5437
  		interactor 3	Alternative splicing, Plasmid
  Contig53177_RC		CDNA FLJ90571 fis,		1470	5438
  		clone
  		OVARC1001725,
  		highly similar to
  		Homo sapiens
  		patched related
  		protein TRC8
  		(TRC8) gene.
  Contig53211_RC	FLJ11588	hypothetical protein	Hypothetical protein	1471	5439
  		FLJ11588
  Contig53223	PPP1R15B	protein phosphatase	Hypothetical protein	1472	5440
  		1, regulatory
  		(inhibitor) subunit
  		15B
  Contig53226_RC		hypothetical protein	Hypothetical protein	1473	5441
  		DKFZp762C1112
  Contig53243_RC		hypothetical protein	Hypothetical protein	1474	5442
  		LOC257106
  Contig53253_RC	WWP2	Nedd-4-like	Ubl conjugation pathway, Ligase,	1475	5443
  		ubiquitin-protein	Repeat
  		ligase
  Contig53260_RC		hypothetical protein	Hypothetical protein	1476	5444
  		LOC196264
  Contig53307_RC	LOC51184	Homo sapiens	Hypothetical protein	1477	5445
  		mRNA full length
  		insert cDNA clone
  		EUROIMAGE
  		1635059.
  Contig53323	KIAA1608	KIAA1608	Hypothetical protein	1478	5446
  Contig53342_RC		Transcribed		1479	5447
  		sequences
  Contig53349_RC	FLJ12287	hypothetical protein	Hypothetical protein, Signal,	1480	5448
  		FLJ12287 similar to	Transmembrane, Immunoglobulin
  		semaphorins	domain, Multigene family,
  			Neurogenesis, Developmental
  			protein, Glycoprotein
  Contig53355_RC	MGC10870	hypothetical protein		1481	5449
  		MGC10870
  Contig53410_RC	FLJ14596	chromosome 9 open	Hypothetical protein	1482	5450
  		reading frame 54
  Contig53439_RC	FLJ22457	hypothetical protein	Hypothetical protein	1483	5451
  		FLJ22457
  Contig53460_RC		CDNA FLJ30010 fis,		1484	5452
  		clone
  		3NB692000154
  Contig5348_RC		Transcribed		1485	5453
  		sequence with weak
  		similarity to protein
  		sp: Q13892
  		(H. sapiens)
  		BT33_HUMAN
  		Transcriptionfactor
  		BTF3 homolog
  3
  Contig53517_RC	PJA1	praja 1	Ubl conjugation pathway, Ligase,	1486	5454
  			Zinc-finger, Alternative splicing
  Contig53555_RC		myotubularin related	Hydrolase, Zinc-finger, Alternative	1487	5455
  		protein 3	splicing, Hypothetical protein
  Contig53566_RC	LANCL2	LanC lantibiotic	Hypothetical protein	1488	5456
  		synthetase
  		component C-like 2
  		(bacterial)
  Contig53585_RC	CG005	phosphonoformate	Hypothetical protein	1489	5457
  		immuno-associated
  		protein 5
  Contig53615_RC	MGC4692	hypothetical protein		1490	5458
  		LOC283871
  Contig53635_RC	FLJ39514	sec1 family domain	Hypothetical protein	1491	5459
  		containing 2
  Contig53641_RC	MAGE-E1	melanoma antigen,	Hypothetical protein	1492	5460
  		family D, 4
  Contig53696_RC	MDS006	x 006 protein		1493	5461
  Contig53709_RC		adaptor-related	Golgi stack, Protein transport,	1494	5462
  		protein complex 1,	Transport, Coated pits, Endocytosis,
  		gamma 1 subunit	Polymorphism, 3D-structure,
  			Hypothetical protein
  Contig53719_RC	FLJ30596	hypothetical protein	Hypothetical protein	1495	5463
  		FLJ30596
  Contig53746_RC	DRLM	nucleosome	Hypothetical protein	1496	5464
  		assembly protein 1-
  		like 5
  Contig53819_RC	MGC11296	breast cancer		1497	5465
  		metastasis-
  		suppressor 1-like
  Contig53823_RC	FLJ31295	hypothetical protein	Metal-binding, Zinc, Zinc-finger,	1498	5466
  		FLJ31295	Hypothetical protein
  Contig53829	MGC3123	hypothetical protein	Hypothetical protein	1499	5467
  		MGC3123
  Contig53852_RC	KIAA1577	zinc finger, SWIM	Hypothetical protein	1500	5468
  		domain containing 6
  Contig53884_RC	LOC59346	PDZ and LIM	Hypothetical protein, LIM domain,	1501	5469
  		domain 2 (mystique)	Metal-binding, Zinc
  Contig53909_RC	MGC23947	hypothetical protein	Hypothetical protein	1502	5470
  		MGC23947
  Contig5392_RC		Transcribed		1503	5471
  		sequences
  Contig53944_RC	MI-ER1	putative NFkB	Hypothetical protein	1504	5472
  		activating protein
  		373
  Contig53985_RC	FLJ30596	hypothetical protein	Hypothetical protein	1505	5473
  		FLJ30596
  Contig54010_RC	MDS024	chromosome 6 open		1506	5474
  		reading frame 75
  Contig54012_RC	SAS10	MRNA; cDNA	Hypothetical protein	1507	5475
  		DKFZp686C2051
  		(from clone
  		DKFZp686C2051)
  Contig54048_RC	GC1	solute carrier family	Mitochondrion, Inner membrane,	1508	5476
  		25 (mitochondrial	Repeat, Transmembrane, Transport,
  		carrier: glutamate),	Symport
  		member 22
  Contig54066_RC	DEDD2	death effector	DNA-binding, Hypothetical protein	1509	5477
  		domain containing 2
  Contig54110_RC		splicing factor,	mRNA processing, mRNA splicing,	1510	5478
  		arginine/serine-rich 1	Nuclear protein, RNA-binding,
  		(splicing factor 2,	Repeat, Alternative splicing,
  		alternate splicing	Acetylation, Phosphorylation
  		factor)
  Contig54113_RC	FLJ11785	Rad50-interacting	Hypothetical protein	1511	5479
  		protein 1
  Contig54137_RC		zinc finger protein 84	Transcription regulation, DNA-	1512	5480
  		(HPF2)	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  Contig54184_RC	MGC955	hypothetical protein	Hypothetical protein	1513	5481
  		MGC955
  Contig54317_RC	MGC29956	hypothetical protein	Hypothetical protein	1514	5482
  		MGC29956
  Contig54321_RC	DDX33	DEAH (Asp-Glu-Ala-	Hypothetical protein, ATP-binding,	1515	5483
  		His) box polypeptide	Helicase, Hydrolase
  		33
  Contig54342_RC	MGC13096	hypothetical protein	Cytokine, Disease	1516	5484
  		MGC13096	mutation, Gluconeogenesis, Glycolysis,
  			Growth factor, Isomerase, Neurone
  Contig54371_RC	GKAP42	protein kinase	Hypothetical protein, Kinase	1517	5485
  		anchoring protein
  		GKAP42
  Contig54463_RC		CDNA FLJ12874 fis,		1518	5486
  		clone
  		NT2RP2003769
  Contig54503_RC		kelch-like 11	Hypothetical protein	1519	5487
  		(Drosophila)
  Contig54531_RC		Homo sapienscDNA		1520	5488
  		FLJ38849 fis, clone
  		MESAN2008936.
  Contig54559_RC		ankyrin repeat and	ANK repeat, Repeat	1521	5489
  		BTB (POZ) domain
  		containing 1
  Contig54563_RC	KNSL5	kinesin family	Motor protein, Cell division,	1522	5490
  		member 23	Microtubule, ATP-binding, Coiled
  			coil, Mitosis, Cell cycle, Nuclear
  			protein
  Contig54581_RC		tumor suppressor		1523	5491
  		TSBF1
  Contig54609_RC	PANK3	pantothenate kinase	3	Transferase, Kinase, ATP-binding,	1524	5492
  			Coenzyme A biosynthesis
  Contig54614_RC	FLJ14007	hypothetical protein	Hypothetical protein	1525	5493
  		FLJ14007
  Contig54659_RC	HCCA2	HCCA2 protein	Hypothetical protein	1526	5494
  Contig54667_RC	ERAP140	nuclear receptor	Receptor, Hypothetical protein	1527	5495
  		coactivator 7
  Contig54680_RC		nucleotide-binding	Hypothetical protein	1528	5496
  		oligomerization
  		domains 27
  Contig54686_RC		zinc finger protein	Hypothetical protein	1529	5497
  		598
  Contig54716_RC	KIAA0863	KIAA0863 protein	Hypothetical protein, Metal-binding,	1530	5498
  			Zinc, Zinc-finger
  Contig54718_RC	FLJ37562	hypothetical protein	Hypothetical protein	1531	5499
  		FLJ37562
  Contig54729_RC		chromosome 10	Hypothetical protein	1532	5500
  		open reading frame
  		30
  Contig54751_RC	VIK	vav-1 interacting	Metal-binding, Zinc, Zinc-finger,	1533	5501
  		Kruppel-like protein	Hypothetical protein
  Contig54757_RC		hypothetical protein	Hypothetical protein	1534	5502
  		LOC129293
  Contig54802_RC	GPR108	G protein-coupled	Hypothetical protein	1535	5503
  		receptor 108
  Contig54829_RC	TJP3	tight junction protein	Hypothetical protein	1536	5504
  		3 (zona occludens 3)
  Contig54893_RC	APOBEC3G	apolipoprotein B	Hypothetical protein	1537	5505
  		mRNA editing
  		enzyme, catalytic
  		polypeptide-like 3G
  Contig54915_RC	DR1	Hypothetical gene	Transcription, Phosphorylation,	1538	5506
  		supported by	Nuclear protein, 3D-structure
  		AL832786
  		(LOC400762),
  		mRNA
  Contig54932_RC	BIVM	basic,	Hypothetical protein	1539	5507
  		immunoglobulin-like
  		variable motif
  		containing
  Contig54961_RC		lemur tyrosine	Hypothetical protein, ATP-binding,	1540	5508
  		kinase 2	Kinase, Transferase, Tyrosine-
  			protein kinase
  Contig5498_RC	C17orf26	solute carrier family	Hypothetical protein	1541	5509
  		39 (metal ion
  		transporter),
  		member 11
  Contig54999_RC	FLJ12994	hypothetical protein	Hypothetical protein	1542	5510
  		FLJ12994
  Contig55004	DKFZP564O0463	mitochondrial folate	Mitochondrion, Inner membrane,	1543	5511
  		transporter/carrier	Repeat, Transmembrane, Transport
  Contig55022_RC	ALP	asparaginase like 1	Hypothetical protein	1544	5512
  Contig55038_RC	MCOLN1	mucolipin 1	Ionic channel, Transmembrane,	1545	5513
  			Hypothetical protein
  Contig55044_RC	DECR2	2,4-dienoyl CoA	Oxidoreductase, Hypothetical protein	1546	5514
  		reductase 2,
  		peroxisomal
  Contig55069_RC		Hypothetical gene		1547	5515
  		supported by
  		BC040598
  		(LOC400960),
  		mRNA
  Contig55079_RC	FLJ21613	corneal wound	Hypothetical protein	1548	5516
  		healing-related
  		protein
  Contig55114_RC		chromosome 6 open	Hypothetical protein	1549	5517
  		reading frame 89
  Contig55121_RC	P5326	hypothetical protein	Hypothetical protein	1550	5518
  		p5326
  Contig5513_RC		Transcribed		1551	5519
  		sequences
  Contig55181_RC	LOC115509	hypothetical protein	Hypothetical protein, Metal-binding,	1552	5520
  		BC014000	Zinc, Zinc-finger
  Contig55193_RC	HS6ST1	heparan sulfate 6-O-	Transferase	1553	5521
  		sulfotransferase 1
  Contig55254_RC	LOC220074	Hypothetical 55.1 kDa		1554	5522
  		protein F09G8.5
  		in chromosome III
  Contig55265_RC		ets variant gene 6	Transcription regulation, Repressor,	1555	5523
  		(TEL oncogene)	Nuclear protein, DNA-binding,
  			Phosphorylation, Proto-oncogene,
  			Chromosomal translocation, 3D-
  			structure
  Contig55334_RC	DKFZp547C195	hypothetical protein	Hypothetical protein	1556	5524
  		DKFZp547C195
  Contig55337_RC	MGC2454	chromosome 2 open	Hypothetical protein,	1557	5525
  		reading frame 8	Methyltransferase, Transferase
  Contig55351_RC		hypothetical protein	Hypothetical protein	1558	5526
  		MGC45871
  Contig55365_RC		CDNA clone		1559	5527
  		IMAGE: 6702802,
  		partial cds
  Contig55375_RC	C1QTNF6	C1q and tumor	Collagen, Signal	1560	5528
  		necrosis factor
  		related protein 6
  Contig55377_RC	DKFZp761H0421	RUN domain	Hypothetical protein	1561	5529
  		containing 1
  Contig55397_RC	CSPG6	sterile alpha motif	Hypothetical protein, ANK repeat,	1562	5530
  		domain containing 6	Repeat
  Contig55468_RC		solute carrier family	Hypothetical protein	1563	5531
  		9 (sodium/hydrogen
  		exchanger),isoform 9
  Contig55487_RC		solute carrier family	Hypothetical protein	1564	5532
  		39 (zinc transporter),
  		member 10
  Contig55522		LOC400236		1565	5533
  		(LOC400236),
  		mRNA
  Contig55539_RC		GAAI470	Hypothetical protein	1566	5534
  Contig55574_RC	KIAA1940	KIAA1940 protein	Hypothetical protein	1567	5535
  Contig55575_RC	SDS3	likely ortholog of	Hypothetical protein	1568	5536
  		mouse Sds3
  Contig55618_RC	MGC4825	hypothetical protein	Hypothetical protein	1569	5537
  		MGC4825
  Contig55671_RC		nuclear factor of	Transcription regulation, Activator,	1570	5538
  		activated T-cells,	Nuclear protein, DNA-binding,
  		cytoplasmic,	Alternative splicing, Phosphorylation,
  		calcineurin-	Repeat, 3D-structure
  		dependent 2
  Contig55674_RC	DUSP16	LOC387840	Hydrolase, Nuclear protein,	1571	5539
  		(LOC387840),	Hypothetical protein
  		mRNA
  Contig55709_RC		chromosome 14		1572	5540
  		open reading frame
  		35
  Contig55712_RC		hypothetical protein	Hypothetical protein	1573	5541
  		LOC286257
  Contig55744_RC	DIRC2	disrupted in renal	Hypothetical protein	1574	5542
  		carcinoma 2
  Contig55759_RC		hypothetical protein	Repeat, ANK repeat, Alternative	1575	5543
  		LOC145758	splicing
  Contig55766_RC	TOMM70A	hypothetical protein	Mitochondrion, Outer membrane,	1576	5544
  		LOC348801	Transmembrane, Repeat, TPR
  			repeat
  Contig55767_RC	FLJ22662	hypothetical protein	Hypothetical protein	1577	5545
  		FLJ22662
  Contig55814_RC		protein containing		1578	5546
  		single MORN motif
  		in testis
  Contig55886_RC		zinc finger protein		1579	5547
  		181 (HHZ181)
  Contig55940_RC	MGC13010	hypothetical protein	Hypothetical protein	1580	5548
  		MGC13010
  Contig55944_RC	FLJ20958	MRNA; cDNA	Hypothetical protein	1581	5549
  		DKFZp686A1197
  		(from clone
  		DKFZp686A1197)
  Contig55950_RC	FLJ22329	hypothetical protein	Hypothetical protein	1582	5550
  		FLJ22329
  Contig55966_RC	DKFZP762N2316	zinc finger protein	Hypothetical protein, Metal-binding,	1583	5551
  		462	Zinc, Zinc-finger
  Contig55979_RC	MGC14136	chromosome 21	Hypothetical protein	1584	5552
  		open reading frame
  		119
  Contig55_RC		protein kinase, AMP-	Fatty acid biosynthesis,	1585	5553
  		activated,beta 2	Phosphorylation
  		non-catalytic subunit
  Contig56036_RC	CD47	CD47 antigen (Rh-	Integrin, Cell adhesion, Antigen,	1586	5554
  		related antigen,	Signal, Transmembrane,
  		integrin-associated	Glycoprotein, Alternative splicing
  		signal transducer)
  Contig56052_RC		hypothetical protein		1587	5555
  		LOC203547
  Contig56056_RC	TRUB1	TruB pseudouridine		1588	5556
  		(psi) synthase
  		homolog 1 (E. coli)
  Contig56061_RC	DEF6	differentially		1589	5557
  		expressed in FDCP
  		6 homolog (mouse)
  Contig56082_RC	RNU2	Homo sapiens	Hypothetical protein	1590	5558
  		mRNA; cDNA
  		DKFZp666D074
  		(from clone
  		DKFZp666D074).
  Contig56147_RC		hypothetical protein	Hypothetical protein	1591	5559
  		LOC338799
  Contig56167_RC	BAALC	brain and acute	Hypothetical protein	1592	5560
  		leukemia,
  		cytoplasmic
  Contig56179_RC	MGC15523	hypothetical protein	Hypothetical protein	1593	5561
  		MGC15523
  Contig56229		likely ortholog of	Hypothetical protein	1594	5562
  		mouse zinc finger
  		protein EZI
  Contig56234_RC	IMAGE3451454	SVAP1 protein	Hypothetical protein	1595	5563
  Contig56242_RC	FLJ23221	hypothetical protein	Hypothetical protein	1596	5564
  		FLJ23221
  Contig56253_RC	FLJ21087	brix domain	Nuclear protein	1597	5565
  		containing 1
  Contig56263_RC	FLJ21080	SET and MYND	Zinc-finger, Hypothetical protein	1598	5566
  		domain containing 3
  Contig56298_RC	FLJ13154	hypothetical protein	Hypothetical protein	1599	5567
  		FLJ13154
  Contig56303_RC	LOC51112	v-abl Abelson	Transferase, Tyrosine-protein	1600	5568
  		murine leukemia	kinase, Proto-oncogene, ATP-
  		viral oncogene	binding, Phosphorylation, SH2
  		homolog 2 (arg,	domain, SH3 domain, Alternative
  		Abelson-related	splicing
  		gene)
  Contig56334_RC	RAI16	retinoic acid induced	Hypothetical protein	1601	5569
  		16
  Contig56350_RC	MGC4607	cerebral cavernous	Hypothetical protein	1602	5570
  		malformation 2
  Contig56390_RC	MGC26847	sushi domain		1603	5571
  		containing 3
  Contig56395_RC	FLJ14624	hypothetical protein	Hypothetical protein	1604	5572
  		FLJ14624
  Contig5639_RC		phosphorylase,	Transferase, Glycosyltransferase,	1605	5573
  		glycogen; liver (Hers	Carbohydrate metabolism, Glycogen
  		disease, glycogen	metabolism, Allosteric enzyme,
  		storage disease type	Pyridoxal phosphate,
  		VI)	Phosphorylation, Glycogen storage
  			disease, Disease mutation,
  			Polymorphism, 3D-structure
  Contig56503_RC	MGC9753	CAB2 protein	Hypothetical protein	1606	5574
  Contig56527_RC		FLJ20758 protein	Hypothetical protein	1607	5575
  Contig56541_RC	LSFR2	dolichyl		1608	5576
  		pyrophosphate
  		phosphatase
  1
  Contig56544_RC	H3F3A	hypothetical protein	Nuclear protein, Chromosomal	1609	5577
  		FLJ20403	protein, DNA-binding, Nucleosome
  			core, Multigene family
  Contig56572_RC	DKFZP564B1162	hypothetical protein	Hypothetical protein	1610	5578
  		DKFZp564B1162
  Contig56583_RC	PF20	PF20	Repeat, WD repeat, Hypothetical	1611	5579
  			protein
  Contig56587_RC	HDAC10	histone deacetylase	Hydrolase, Nuclear protein,	1612	5580
  		10	Chromatin regulator, Transcription
  			regulation, Repressor,
  			Polymorphism, Alternative splicing
  Contig565_RC		CDNA FLJ31683 fis,		1613	5581
  		clone
  		NT2RI2005353
  Contig56623_RC		Cas-Br-M (murine)	Hypothetical protein, Ligase, Ubl	1614	5582
  		ecotropic retroviral	conjugation pathway, Proto-
  		transforming	oncogene, Zinc-finger, SH2 domain,
  		sequence	Phosphorylation, Calcium-binding,
  			3D-structure
  Contig56662_RC	MGC10963	THAP domain	Zinc-finger, DNA-binding	1615	5583
  		containing 7
  Contig56671_RC	FLJ12761	mSin3A-associated	Hypothetical protein	1616	5584
  		protein 130
  Contig56716_RC	KIAA1754	KIAA1754	Hypothetical protein	1617	5585
  Contig56735_RC		CDNA FLJ90790 fis,	Hypothetical protein	1618	5586
  		clone
  		THYRO1001529,
  		weakly similar to
  		SERINE
  		PALMITOYLTRANSFERASE
  		2 (EC
  		2.3.1.50).
  Contig56781_RC	MGC11349	hypothetical protein	Hypothetical protein, Metal-binding,	1619	5587
  		MGC11349	Zinc, Zinc-finger
  Contig56823_RC		Transcribed		1620	5588
  		sequence with
  		moderate similarity
  		to protein
  		ref: NP_060265.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20378 [Homo
  		sapiens]
  Contig56944_RC	ASH1	ash1 (absent, small,	Hypothetical protein	1621	5589
  		or homeotic)-like
  		(Drosophila)
  Contig57011_RC	CDA11	CDA11 protein	Hypothetical protein	1622	5590
  Contig57017_RC	TFB2M	transcription factor	Hypothetical protein	1623	5591
  		B2, mitochondrial
  Contig57036_RC		hypothetical protein	Fatty acid biosynthesis, Biotin,	1624	5592
  		LOC283445	Ligase, Multifunctional enzyme,
  			ATP-binding, Phosphorylation,
  			Alternative splicing
  Contig57057_RC	MAP3K3	hypothetical protein	Hypothetical protein, LIM domain,	1625	5593
  		MGC10986	Metal-binding, Zinc
  Contig57076_RC	FBXO32	F-box only protein	Ubl conjugation pathway	1626	5594
  		32
  Contig57081_RC	MSI2	musashi homolog	2	Hypothetical protein	1627	5595
  		(Drosophila)
  Contig57090_RC		Full length insert		1628	5596
  		cDNA clone
  		YZ93G08
  Contig5716_RC		CDNA FLJ38396 fis,		1629	5597
  		clone
  		FEBRA2007957
  Contig57173_RC	KIAA1737	KIAA1737	Hypothetical protein	1630	5598
  Contig571_RC	ST6GALNAC6	CMP-NeuAC:(beta)-	Glycosyltransferase, Transferase,	1631	5599
  		N-	Hypothetical protein
  		acetylgalactosaminide
  		(alpha)2,6-
  		sialyltransferase
  		member VI
  Contig57226_RC		tubulin, beta, 2	GTP-binding, Hypothetical protein,	1632	5600
  			Microtubule, Multigene family
  Contig57239_RC	EPI64	KIAA0114 gene	Hypothetical protein	1633	5601
  		product
  Contig57270_RC	ABCC4	ATP-binding	ATP-binding, Glycoprotein,	1634	5602
  		cassette, sub-family	Transmembrane, Transport, Repeat
  		C (CFTR/MRP),
  		member 4
  Contig57290_RC		hypothetical protein		1635	5603
  		LOC286334
  Contig57417	LOC80298	transcription	Hypothetical protein	1636	5604
  		termination factor-
  		like protein
  Contig57436_RC	PPP2R5E	protein phosphatase	Phosphorylation, Multigene family	1637	5605
  		2, regulatory subunit
  		B (B56), epsilon
  		isoform
  Contig57458_RC	IL6R	interleukin	6 receptor	Receptor, Transmembrane,	1638	5606
  			Glycoprotein, Immunoglobulin
  			domain, Repeat, Alternative splicing,
  			Signal, 3D-structure
  Contig57493_RC	MGC4399	mitochondrial carrier		1639	5607
  		protein
  Contig57562_RC	M11S1	membrane	GPI-anchor	1640	5608
  		component,
  		chromosome 11,
  		surface marker 1
  Contig57579	ABTB1	ankyrin repeat and	ANK repeat, Repeat	1641	5609
  		BTB (POZ) domain
  		containing 1
  Contig57625_RC	FLJ14225	polycystic kidney	Hypothetical protein	1642	5610
  		disease 1-like
  Contig57822_RC		CDNA clone		1643	5611
  		IMAGE: 5286019,
  		partial cds
  Contig57825_RC	MGC18216	hypothetical protein	Hypothetical protein	1644	5612
  		MGC18216
  Contig57840_RC	MBP	CDNA clone	Hypothetical protein, Myelin,	1645	5613
  		MGC: 70813	Structural protein, Acetylation,
  		IMAGE: 6060520,	Methylation, Phosphorylation,
  		complete cds	Citrullination, Autoimmune
  			encephalomyelitis, 3D-structure,
  			Alternative splicing
  Contig57957_RC	COL5A2	similar to RIKEN	Hypothetical protein	1646	5614
  		cDNA 5730578N08
  		gene
  Contig58042_RC		CDNA FLJ39602 fis,		1647	5615
  		clone
  		SKNSH2005061
  Contig58113_RC	FLJ14005	hypothetical protein	Hypothetical protein	1648	5616
  		LOC286044
  Contig58123_RC	NFYB	nuclear transcription	Transcription regulation, DNA-	1649	5617
  		factor Y, beta	binding, Activator, Nuclear protein,
  			3D-structure
  Contig58145_RC	YEA	solute carrier family	Hypothetical protein	1650	5618
  		35, member B4
  Contig58156_RC	C20orf167	deoxynucleotidyltransferase,	Nuclear protein, Polymorphism	1651	5619
  		terminal,
  		interactingprotein 1
  Contig58193_RC	TCF7L2	transcription factor	Transcription regulation, Activator,	1652	5620
  		7-like 2 (T-cell	Repressor, Trans-acting factor,
  		specific, HMG-box)	Nuclear protein, DNA-binding, Wnt
  			signaling pathway, Alternative
  			splicing, 3D-structure, Hypothetical
  			protein
  Contig58212_RC	PPARBP	PPAR binding	DNA-binding, Transcription	1653	5621
  		protein	regulation, Activator, Repeat,
  			Nuclear protein, Alternative splicing
  Contig58249_RC	moblak	MOB1, Mps One	Hypothetical protein	1654	5622
  		Binder kinase
  		activator-like 2A
  		(yeast)
  Contig58260_RC	DGAT2	diacylglycerol O-	Hypothetical protein,	1655	5623
  		acyltransferase	Acyltransferase, Transferase
  		homolog 2 (mouse)
  Contig58275_RC		general transcription		1656	5624
  		factor IIIC,
  		polypeptide 4,
  		90 kDa
  Contig58288_RC	LOC89941	ras homolog gene	Hypothetical protein, GTP-binding	1657	5625
  		family, member T2
  Contig58339_RC	FLJ21616	MRNA; cDNA	Hypothetical protein	1658	5626
  		DKFZp686E1648
  		(from clone
  		DKFZp686E1648)
  Contig58353_RC	FLJ13089	hypothetical protein	Hypothetical protein	1659	5627
  		FLJ13089
  Contig58491_RC	TRIP11	ah24a06.s1	Hypothetical protein, Antigen, Golgi	1660	5628
  		Soares_parathyroid_tumor_NbHPA	stack, Coiled coil, Chromosomal
  		Homo sapienscDNA	translocation
  		clone 1239730 3′,
  		mRNA sequence.
  Contig58530_RC	KIAA1560	glycerol 3-phosphate	Hypothetical protein, Phospholipid	1661	5629
  		acyltransferase,	biosynthesis, Transferase,
  		mitochondrial	Acyltransferase, Transmembrane,
  			Mitochondrion, Transit peptide
  Contig58595_RC	AP1M1	adaptor-related	Golgi stack, Protein transport,	1662	5630
  		protein complex 1,	Transport, Coated pits, Endocytosis,
  		mu 1 subunit	Phosphorylation
  Contig58613	VPS4B	vacuolar protein	ATP-binding	1663	5631
  		sorting 4B (yeast)
  Contig58966_RC	HLA-F	major	MHC	1664	5632
  		histocompatibility
  		complex, class I, F
  Contig59120_RC	FLJ37080	adhesion molecule	Hypothetical protein	1665	5633
  		AMICA
  Contig59127_RC	PCF11	pre-mRNA cleavage	mRNA processing, Nuclear protein	1666	5634
  		complex II protein
  		Pcf11
  Contig59134_RC		hypothetical protein		1667	5635
  		LOC283481
  Contig59136_RC		qp75d05.x1		1668	5636
  		Soares_fetal_lung_NbHL19W
  		Homo
  		sapienscDNA clone
  		IMAGE: 1928841 3′
  		similar to gb: D14531
  		60S RIBOSOMAL
  		PROTEIN L9
  		(HUMAN); mRNA
  		sequence.
  Contig59187_RC	NUDT3	nudix (nucleoside	Hydrolase	1669	5637
  		diphosphate linked
  		moiety X)-type motif 3
  Contig5954_RC		similar to RIKEN	Hypothetical protein, Iron, Iron-sulfur	1670	5638
  		cDNA B230118G17
  		gene
  Contig60075	FLJ32468	ESTs		1671	5639
  Contig60315_RC	MGC39807	organic solute	Hypothetical protein	1672	5640
  		transporter alpha
  Contig6041_RC		Transcribed		1673	5641
  		sequences
  Contig60509_RC		GL004 protein	Hypothetical protein	1674	5642
  Contig60612_RC		xylosyltransferase I	Transferase, Glycosyltransferase	1675	5643
  Contig6064_RC		Colorectal cancer-		1676	5644
  		related mRNA
  		sequence
  Contig60981_RC		p10-binding protein	Hypothetical protein	1677	5645
  Contig61061_RC	RASGRP4	RAS guanyl	Hypothetical protein	1678	5646
  		releasingprotein 4
  Contig6113_RC		CDNA FLJ30090 fis,		1679	5647
  		clone
  		BNGH41000015
  Contig61227_RC		hypothetical protein	Hypothetical protein, Repeat, WD	1680	5648
  		FLJ10055	repeat
  Contig61254_RC	MGC5352	hypothetical protein	Hypothetical protein	1681	5649
  		MGC5352
  Contig61264_RC	KIAA1833	hypothetical protein	Hypothetical protein	1682	5650
  		KIAA1833
  Contig61267_RC	C20orf126	chromosome 20	Hypothetical protein	1683	5651
  		open reading frame
  		126
  Contig61815	LOC51063	hypothetical protein	Hypothetical protein	1684	5652
  		LOC51063
  Contig61848_RC		Transcribed		1685	5653
  		sequence with weak
  		similarity to protein
  		ref: NP_060312.1
  		(H. sapiens)
  		hypothetical protein
  		FLJ20489 [Homo
  		sapiens]
  Contig61915_RC	MGC2803	hypothetical protein	Hypothetical protein	1686	5654
  		MGC2803
  Contig61975	MGC11242	hypothetical protein	Hypothetical protein	1687	5655
  		MGC11242
  Contig62149_RC		chromosome 22	Hypothetical protein	1688	5656
  		open reading frame
  		23
  Contig6254_RC		Transcribed		1689	5657
  		sequences
  Contig62568_RC	MRPL24	mitochondrial	Ribosomal protein, Hypothetical	1690	5658
  		ribosomal protein	protein
  		L24
  Contig62588_RC		hypothetical protein	DNA-binding, Metal-binding, Nuclear	1691	5659
  		LOC284323	protein, Zinc-finger
  Contig62628_RC	EIF3S9	eukaryotic	Hypothetical protein, Initiation factor,	1692	5660
  		translation initiation	Protein biosynthesis, RNA-binding
  		factor
  3,subunit 9
  		eta, 116 kDa
  Contig62675_RC		similar to RIKEN	Hypothetical protein	1693	5661
  		1810056O20
  Contig62923_RC	FLJ12697	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	1694	5662
  		protease 42	Thiol protease, Multigene family
  Contig63026		hypothetical protein		1695	5663
  		LOC285958
  Contig63079	FLJ32332	likely ortholog of	Hypothetical protein	1696	5664
  		mouse protein
  		phosphatase 2C eta
  Contig6323_RC	FLJ12581	Nanog homeobox	DNA-binding, Homeobox, Nuclear	1697	5665
  			protein, Hypothetical protein
  Contig63304	LOC113444	hypothetical protein	Hypothetical protein	1698	5666
  		BC011880
  Contig63667_RC	MCPR	hypothetical protein	Ubl conjugation pathway, Cell cycle,	1699	5667
  		LOC285069	Cell division, Mitosis, Repeat
  Contig6382_RC		Transcribed		1700	5668
  		sequences
  Contig63913_RC	MGC13016	coiled-coil-helix-		1701	5669
  		coiled-coil-helix
  		domain containing 6
  Contig64214_RC	MGC19604	similar to RIKEN	Hypothetical protein	1702	5670
  		cDNA B230118G17
  		gene
  Contig64297_RC	KIAA1416	KIAA1416 protein	Hypothetical protein, Transcription	1703	5671
  			regulation, Hydrolase, Helicase,
  			Chromatin regulator, Nuclear
  			protein, ATP-binding, DNA-binding,
  			Repeat
  Contig64390	C20orf92	COMM domain	Hypothetical protein	1704	5672
  		containing 7
  Contig64477		Clone		1705	5673
  		IMAGE: 5742072,
  		mRNA
  Contig64502	KIAA0303	KIAA0303 protein	Hypothetical protein, ATP-binding,	1706	5674
  			Kinase, Serine/threonine-protein
  			kinase, Transferase
  Contig64691	UBB	ubiquitin B	Hypothetical protein	1707	5675
  Contig64794	FLJ21156	Homo sapiens	Hypothetical protein	1708	5676
  		cDNA: FLJ21156 fis,
  		clone CAS09878.
  Contig64940_RC	ORAOV1	oral cancer	Hypothetical protein	1709	5677
  		overexpressed 1
  Contig65300_RC		CDNA FLJ41454 fis,		1710	5678
  		clone
  		BRSTN2011597
  Contig65404	CKLFSF3	chemokine-like	Chemotaxis, Cytokine,	1711	5679
  		factorsuper family 3	Transmembrane, Alternative splicing
  Contig65439	C20orf178	chromosome 20	Hypothetical protein	1712	5680
  		open reading frame
  		178
  Contig65459_RC		formin binding	Hypothetical protein, SH3 domain	1713	5681
  		protein 1
  Contig65478_RC		phosphoglucomutase	Hypothetical protein	1714	5682
  		2-like 1
  Contig65900	HMGN3	high mobility group	Nuclear protein, DNA-binding,	1715	5683
  		nucleosomal binding	Hypothetical protein
  		domain
  3
  Contig65934_RC		hypothetical gene	Hypothetical protein	1716	5684
  		supported by
  		BC031661
  Contig66003_RC	MY038	retinoblastoma	Hypothetical protein, Metal-binding,	1717	5685
  		binding protein 6	Zinc, Zinc-finger
  Contig66028_RC		reversion-inducing-	Signal, Glycoprotein, GPI-anchor,	1718	5686
  		cysteine-rich protein	Serine protease inhibitor,
  		with kazal motifs	Membrane, Anti-oncogene, Repeat,
  			Lipoprotein
  Contig66129_RC		CDNA FLJ13276 fis,		1719	5687
  		clone
  		OVARC1001040
  Contig66573_RC	FLJ12567	Clone	Hypothetical protein	1720	5688
  		IMAGE: 5538723,
  		mRNA
  Contig66615_RC	USP9Y	Human S6 H-8	Ubiquitin conjugation, Hydrolase,	1721	5689
  		mRNA expressed in	Thiol protease, Multigene family,
  		chromosome 6-	Alternative splicing
  		suppressed
  		melanoma cells.
  Contig66632_RC		hypothetical protein		1722	5690
  		LOC339324
  Contig66759_RC	MGC16028	MGC16028 similar		1723	5691
  		to RIKEN cDNA
  		1700019E19 gene
  Contig667_RC	ADAM17	hypothetical protein	Hydrolase, Metalloprotease, Zinc,	1724	5692
  		LOC285148	Signal, Glycoprotein, Zymogen,
  			Transmembrane, SH3-binding,
  			Phosphorylation, Alternative splicing,
  			3D-structure
  Contig66868_RC		ze63e05.s1 Soares		1725	5693
  		retina N2b4HR
  		Homo sapienscDNA
  		clone
  		IMAGE: 363680 3′,
  		mRNA sequence.
  Contig66904_RC	MGC4368	hypothetical protein	Hypothetical protein	1726	5694
  		MGC4368
  Contig684_RC	RPS3A	ring finger protein 12	Transcription regulation, Zinc-finger,	1727	5695
  			Hypothetical protein, Metal-binding
  Contig693_RC	NFIA	nuclear factor I/A	Activator, DNA replication, DNA-	1728	5696
  			binding, Nuclear protein,
  			Transcription, Transcription
  			regulation, Multigene family
  Contig706_RC		CDNA FLJ32401 fis,		1729	5697
  		clone
  		SKMUS2000339
  Contig726_RC	FLJ13725	hypothetical protein	Hypothetical protein	1730	5698
  		FLJ13725
  Contig732_RC	FTH1	transducer of	Hypothetical protein	1731	5699
  		regulated cAMP
  		response element-
  		binding protein
  		(CREB) 2
  Contig7401_RC	FLJ22756	PDZ domain	Hypothetical protein	1732	5700
  		containing 2
  Contig75_RC	RPS6KA2	ribosomal protein S6	ATP-binding, Kinase,	1733	5701
  		kinase, 90 kDa,	Serine/threonine-protein kinase,
  		polypeptide 2	Transferase, Repeat, Multigene
  			family, Phosphorylation, Nuclear
  			protein
  Contig773	FLJ20989	hypothetical protein	Hypothetical protein	1734	5702
  		FLJ20989
  Contig8210_RC	DJ467N11.1	dJ467N11.1 protein	ATP-binding, Helicase, Hydrolase,	1735	5703
  			Hypothetical protein
  Contig830_RC	C1orf13	N-acetylneuraminate		1736	5704
  		pyruvate lyase
  		(dihydrodipicolinate
  		synthase)
  Contig8371_RC		Transcribed		1737	5705
  		sequences
  Contig842_RC		human T-cell	Transcription regulation, DNA-	1738	5706
  		leukemia virus	binding, Nuclear protein
  		enhancer factor
  Contig844_RC	DKFZP566M1046	hypothetical protein	Hypothetical protein	1739	5707
  		DKFZp566M1046
  Contig8547_RC		Transcribed		1740	5708
  		sequences
  Contig883_RC	KIAA1813	KIAA1813 protein	Hypothetical protein	1741	5709
  Contig8885_RC	HCS	cytochrome c,	Mitochondrion, Electron transport,	1742	5710
  		somatic	Respiratory chain, Heme,
  			Acetylation, Polymorphism,
  			Apoptosis
  Contig8909_RC	MGC45404	TAK1-binding	Hypothetical protein	1743	5711
  		protein 3
  Contig8956_RC	FLJ13158	chromosome 6 open	Hypothetical protein	1744	5712
  		reading frame 134
  Contig8963_RC		wi72b03.x1		1745	5713
  		NCI_CGAP_Kid12
  		Homo sapienscDNA
  		clone
  		IMAGE: 2398829 3′,
  		mRNA sequence.
  Contig8980_RC	DKFZP564B1162	hypothetical protein	Hypothetical protein	1746	5714
  		DKFZp564B1162
  Contig9042_RC		Transcribed		1747	5715
  		sequences
  Contig9059_RC	FLJ12118	hypothetical protein	Hypothetical protein	1748	5716
  		FLJ12118
  Contig9136_RC		CDNA FLJ43053 fis,		1749	5717
  		clone
  		BRTHA3006856
  Contig9380_RC		Transcribed		1750	5718
  		sequences
  Contig9514_RC		Transcribed		1751	5719
  		sequences
  Contig9518_RC	ZNF287	zinc finger protein	Metal-binding, Zinc, Zinc-finger,	1752	5720
  		287	Transcription regulation, Nuclear
  			protein, DNA-binding, Repeat
  Contig964_RC	MGC10433	hypothetical protein	Hypothetical protein	1753	5721
  		MGC10433
  Contig9714_RC		MRNA for	Hypothetical protein	1754	5722
  		hypothetical protein
  		(ORF1), clone 00275
  Contig973_RC	MRPL45	mitochondrial	Ribosomal protein, Mitochondrion,	1755	5723
  		ribosomal protein	Transit peptide
  		L45
  Contig9810_RC	KCNE1	potassium voltage-	Transport, Ion transport, Ionic	1756	5724
  		gated channel, lsk-	channel, Voltage-gated channel,
  		related family,	Potassium channel, Potassium,
  		member 1	Potassium transport,
  			Transmembrane, Phosphorylation,
  			Glycoprotein, Polymorphism,
  			Disease mutation, Long QT
  			syndrome, Deafness
  Contig9965_RC	DHODH	dihydroorotate	Pyrimidine biosynthesis,	1757	5725
  		dehydrogenase	Oxidoreductase, Flavoprotein, FAD,
  			Transit peptide, Mitochondrion, 3D-
  			structure
  D10040	FACL2	acyl-CoA synthetase	Ligase, Fatty acid metabolism,	1758	5726
  		long-chain family	Magnesium, Multigene family,
  		member 1	Hypothetical protein
  D13642	SF3B3	splicing factor 3b,	Spliceosome, mRNA processing,	1759	5727
  		subunit 3, 130 kDa	mRNA splicing, Nuclear protein,
  			Hypothetical protein
  D16816	REG1B	regenerating islet-	Glycoprotein, Signal, Lectin,	1760	5728
  		derived 1 beta	Pyrrolidone carboxylic acid
  		(pancreatic stone
  		protein, pancreatic
  		thread protein)
  D21064	INPP5E	peptidase	Hypothetical protein, Hydrolase,	1761	5729
  		(mitochondrial	Metalloprotease, Mitochondrion,
  		processing) alpha	Transit peptide
  D25218	RRS1	RRS1 ribosome	Ribosome biogenesis, Nuclear	1762	5730
  		biogenesis regulator	protein
  		homolog (S. cerevisiae)
  D25328	PFKP	phosphofructokinase,	Kinase, Transferase, Glycolysis,	1763	5731
  		platelet	Repeat, Allosteric enzyme,
  			Phosphorylation, Magnesium,
  			Multigene family
  D26070	ITPR1	inositol 1,4,5-	Receptor, Transmembrane,	1764	5732
  		triphosphate	Phosphorylation, Endoplasmic
  		receptor,type 1	reticulum, Ionic channel, Ion
  			transport, Calcium channel,
  			Alternative splicing, Repeat
  D26362	BRD3	bromodomain	Bromodomain, Repeat, Nuclear	1765	5733
  		containing 3	protein
  D26488	KIAA0007	KIAA0007 protein	Hypothetical protein, Repeat, WD	1766	5734
  			repeat
  D29954	KIAA0056	KIAA0056 protein	Hypothetical protein	1767	5735
  D29958	KIAA0116	KIAA0116 protein	Exosome, Hydrolase, Nuclease,	1768	5736
  			Exonuclease, rRNA processing,
  			Nuclear protein, RNA-binding,
  			Polymorphism, Hypothetical protein
  D31886	RAB3GAP	RAB3 GTPase-	Hypothetical protein	1769	5737
  		ACTIVATING
  		PROTEIN
  D31887	KIAA0062	solute carrier family	Hypothetical protein	1770	5738
  		39 (zinc transporter),
  		member 14
  D38435	PMS2L1	postmeiotic	Hypothetical protein, DNA repair,	1771	5739
  		segregation	Anti-oncogene, Nuclear protein,
  		increased 2-like 6	Polymorphism, Disease mutation,
  			Hereditary nonpolyposis colorectal
  			cancer, 3D-structure
  D38522	SYT11	Homo sapiens	Transmembrane, Repeat, Synapse,	1772	5740
  		KIAA0080 mRNA,	Hypothetical protein
  		partial cds.
  D38549	CYFIP1	cytoplasmic FMR1	Hypothetical protein	1773	5741
  		interactingprotein 1
  D42043	KIAA0084	raft-linking protein	Hypothetical protein	1774	5742
  D42084	METAP1	methionyl	Hydrolase, Aminopeptidase, Cobalt	1775	5743
  		aminopeptidase 1
  D43948	KIAA0097	KIAA0097 gene	Hypothetical protein, Repeat	1776	5744
  		product
  D43949	KIAA0082	KIAA0082	Hypothetical protein	1777	5745
  D50402	SLC11A1	solute carrier family	Transport, Iron transport,	1778	5746
  		11 (proton-coupled	Transmembrane, Glycoprotein,
  		divalent metal ion	Macrophage, Polymorphism
  		transporters),
  		member 1
  D50911	GSA7	KIAA0121 gene	Hypothetical protein	1779	5747
  		product
  D50918	6-Sep	septin 6	Cell division, GTP-binding, Coiled	1780	5748
  			coil, Alternative splicing
  D63487	KIAA0153	KIAA0153 protein	Hypothetical protein	1781	5749
  D79998	KCTD2	potassium channel	Hypothetical protein	1782	5750
  		tetramerisation
  		domain containing 2
  D80007	PDCD11	programmed cell	Nuclear protein, rRNA processing,	1783	5751
  		death 11	Repeat, Polymorphism
  D80010	LPIN1	lipin	1	Nuclear protein, Polymorphism	1784	5752
  D83781	NUP160	nucleoporin 160 kDa	Nuclear protein, Transport,	1785	5753
  			Alternative splicing, Hypothetical
  			protein
  D84294	TTC3	tetratricopeptide	Repeat, TPR repeat, Zinc-finger,	1786	5754
  		repeat domain 3	Alternative splicing, Polymorphism,
  			Metal-binding
  D86964	DOCK2	dedicator of	Guanine-nucleotide releasing factor,	1787	5755
  		cytokinesis 2	Membrane, Cytoskeleton, SH3
  			domain, Alternative splicing,
  			Polymorphism
  D86973	GCN1L1	GCN1 general	Hypothetical protein	1788	5756
  		control of amino-acid
  		synthesis 1-like 1
  		(yeast)
  D86976	HA-1	minor		1789	5757
  		histocompatibility
  		antigen HA-1
  D87442	NCSTN	nicastrin	Transmembrane, Glycoprotein,	1790	5758
  			Signal, Alternative splicing
  D87449	SLC35D1	solute carrier family	Transport, Sugar transport,	1791	5759
  		35 (UDP-glucuronic	Transmembrane, Endoplasmic
  		acid/UDP-N-	reticulum
  		acetylgalactosamine
  		dual transporter),
  		member D1
  D87453	MRPS27	mitochondrial	Hypothetical protein, Ribosomal	1792	5760
  		ribosomal protein	protein, Mitochondrion
  		S27
  D87466	KIAA0276	KIAA0276 protein	Hypothetical protein	1793	5761
  G26403	C9orf19	chromosome 9 open	Hypothetical protein	1794	5762
  		reading frame 19
  J03077	PSAP	prosaposin (variant	Signal, Glycoprotein, Lysosome,	1795	5763
  		Gaucher disease	Sphingolipid metabolism, Repeat,
  		and variant	Gaucher disease, GM2-
  		metachromatic	gangliosidosis, Disease mutation,
  		leukodystrophy)	Metachromatic leukodystrophy,
  			Alternative splicing, 3D-structure
  J03796	EPB41	erythrocyte	Structural protein, Alternative	1796	5764
  		membrane protein	splicing, Cytoskeleton, Actin-binding,
  		band 4.1	Phosphorylation, Pyropoikilocytosis,
  		(elliptocytosis 1, RH-	Glycoprotein, Elliptocytosis,
  		linked)	Hereditary hemolytic anemia,
  			Polymorphism, 3D-structure
  J04162	FCGR3A	Fc fragment of IgG,	Receptor, IgG-binding protein,	1797	5765
  		low affinity IIIa,	Transmembrane, Glycoprotein,
  		receptor for (CD16)	Signal, Immunoglobulin domain,
  			Repeat, Multigene family,
  			Polymorphism, GPI-anchor, 3D-
  			structure, Lipoprotein
  J04178	HEXA	hexosaminidase A	Hydrolase, Glycosidase, Lysosome,	1798	5766
  		(alpha polypeptide)	GM2-gangliosidosis, Signal,
  			Zymogen, Glycoprotein, Disease
  			mutation, Polymorphism, 3D-
  			structure
  K02276	MYC	v-myc	Proto-oncogene, Nuclear protein,	1799	5767
  		myelocytomatosis	DNA-binding, Phosphorylation,
  		viral oncogene	Transcription regulation, Activator,
  		homolog (avian)	Glycoprotein, Polymorphism, 3D-
  			structure
  K02403	C4A	complement	Complement pathway, Plasma,	1800	5768
  		component 4A	Glycoprotein, Sulfation, Signal,
  			Inflammatory response,
  			Polymorphism, Disease mutation,
  			Blood group antigen, Thioester bond
  L00635	FNTB	farnesyltransferase,	Plasmid, Transferase,	1801	5769
  		CAAX box, beta	Prenyltransferase, Repeat, Zinc
  L08246	MCL1	myeloid cell	Apoptosis, Transmembrane,	1802	5770
  		leukemia sequence	Differentiation, Alternative splicing
  		1 (BCL2-related)
  L20688	ARHGDIB	Rho GDP	GTPase activation, 3D-structure	1803	5771
  		dissociation inhibitor
  		(GDI) beta
  L21961	IGL@	Human Ig	Immunoglobulin domain,	1804	5772
  		rearranged lambda-	Hypothetical protein,
  		chain mRNA,	Immunoglobulin C region, 3D-
  		subgroup VL3, V-J	structure
  		region, partial cds.
  L22005	CDC34	cell division cycle 34	Ubl conjugation pathway, Ligase,	1805	5773
  			Multigene family, Hypothetical
  			protein, Cell division
  L27943	CDA	cytidine deaminase	Hydrolase, Zinc	1806	5774
  L35035	RPIA	ribose 5-phosphate	Isomerase	1807	5775
  		isomerase A (ribose
  		5-phosphate
  		epimerase)
  L39061	TAF1B	TATA box binding	Hypothetical protein	1808	5776
  		protein (TBP)-
  		associated factor,
  		RNA polymerase I,
  		B, 63 kDa
  L40027	GSK3A	glycogen synthase	Transferase, Serine/threonine-	1809	5777
  		kinase 3 alpha	protein kinase, ATP-binding,
  			Multigene family, Phosphorylation
  M12679	HLA-C	major	Glycoprotein, Signal,	1810	5778
  		histocompatibility	Transmembrane, Hypothetical
  		complex, class I, C	protein, MHC, MHC I,
  			Polymorphism, 3D-structure,
  			Alternative splicing
  M12758	HLA-C	Human MHC class I	Glycoprotein, Transmembrane	1811	5779
  		HLA-A cell surface
  		antigen mRNA,
  		(HLA-A2,-B7,-C),
  		clone JY103.
  M17733	TMSB4X	thymosin,beta 4, X-	Actin-binding, Cytoskeleton,	1812	5780
  		linked	Acetylation
  M26383	IL8	interleukin	8	Cytokine, Chemotaxis, Inflammatory	1813	5781
  			response, Signal, Alternative
  			splicing, 3D-structure
  M31212	MYL6	myosin, light	Myosin, Muscle protein, Acetylation,	1814	5782
  		polypeptide 6, alkali,	Alternative splicing, Multigene family
  		smooth muscle and
  		non-muscle
  M31523	TCF3	transcription factor	3	Transcription regulation, DNA-	1815	5783
  		(E2A	binding, Nuclear protein, Proto-
  		immunoglobulin	oncogene, Chromosomal
  		enhancer binding	translocation, Alternative splicing,
  		factors E12/E47)	Phosphorylation, 3D-structure
  M33552	LSP1	lymphocyte-specific	T-cell, Phosphorylation,	1816	5784
  		protein 1	Polymorphism
  M34671	CD59	CD59 antigen p18-20	Antigen, Glycoprotein, GPI-anchor,	1817	5785
  		(antigen identified	Signal, 3D-structure, Lipoprotein
  		by monoclonal
  		antibodies 16.3A5,
  		EJ16, EJ30, EL32
  		and G344)
  M37712	CDC2L2	Homo sapiens	Apoptosis, Transferase,	1818	5786
  		p58/GTA protein	Serine/threonine-protein kinase,
  		kinase mRNA,	ATP-binding, Cell cycle,
  		complete cds.	Phosphorylation, Alternative splicing,
  			Alternative initiation
  M60721	HLX1	H2.0-like homeo box	DNA-binding, Homeobox, Nuclear	1819	5787
  		1 (Drosophila)	protein, Transcription regulation
  M63438	IGKC	Immunoglobulin	Hypothetical protein	1820	5788
  		kappa light chain
  		mRNA, partial cds
  M65292	HFL1	H factor	Repeat, Glycoprotein, Sushi, Signal,	1821	5789
  		(complement)-like 1	Polymorphism
  M74782	IL3RA	interleukin	3	Receptor, Transmembrane,	1822	5790
  		receptor, alpha (low	Glycoprotein, Signal
  		affinity)
  M83822	LRBA	LPS-responsive	Repeat, WD repeat	1823	5791
  		vesicle trafficking,
  		beach and anchor
  		containing
  M90657	TM4SF1	Human tumor	Glycoprotein, Antigen,	1824	5792
  		antigen (L6) mRNA,	Transmembrane
  		complete cds.
  M91211	AGER	advanced	Immunoglobulin domain,	1825	5793
  		glycosylation end	Glycoprotein, Transmembrane,
  		product-specific	Repeat, Signal, Alternative splicing,
  		receptor	Polymorphism, Receptor
  M92439	LRPPRC	leucine-rich PPR-	Hypothetical protein, Repeat	1826	5794
  		motif containing
  M92642	COL16A1	collagen, type XVI,	Extracellular matrix, Connective	1827	5795
  		alpha 1	tissue, Collagen, Hydroxylation,
  			Repeat, Signal
  M94362	LMNB2	Human lamin B2	Intermediate filament, Coiled coil,	1828	5796
  		(LAMB2) mRNA,	Nuclear protein, Lipoprotein,
  		partial cds.	Prenylation, Phosphorylation,
  			Hypothetical protein
  NM_000016	ACADM	acyl-Coenzyme A	Oxidoreductase, Flavoprotein, FAD,	1829	5797
  		dehydrogenase, C-4	Fatty acid metabolism,
  		to C-12 straight	Mitochondrion, Transit peptide,
  		chain	Disease mutation, 3D-structure
  NM_000018	ACADVL	acyl-Coenzyme A	Oxidoreductase, Flavoprotein, FAD,	1830	5798
  		dehydrogenase, very	Fatty acid metabolism,
  		long chain	Mitochondrion, Transit peptide,
  			Alternative splicing, Disease
  			mutation, Polymorphism,
  			Cardiomyopathy
  NM_000021	PSEN1	presenilin 1	Transmembrane, Phosphorylation,	1831	5799
  		(Alzheimer disease	Endoplasmic reticulum, Golgi stack,
  		3)	Alzheimer's disease, Disease
  			mutation, Polymorphism, Alternative
  			splicing
  NM_000022	ADA	adenosine	Hydrolase, Nucleotide metabolism,	1832	5800
  		deaminase	SCID, Hereditary hemolytic anemia,
  			Disease mutation, Polymorphism
  NM_000026	ADSL	adenylosuccinate	Purine biosynthesis, Lyase,	1833	5801
  		lyase	Alternative splicing, Disease
  			mutation, Epilepsy
  NM_000030	AGXT	alanine-glyoxylate	Aminotransferase, Transferase,	1834	5802
  		aminotransferase	Pyridoxal phosphate, Peroxisome,
  		(oxalosis I;	Mitochondrion, Disease mutation,
  		hyperoxaluria I;	Polymorphism
  		glycolicaciduria;
  		serine-pyruvate
  		aminotransferase)
  NM_000034	ALDOA	aldolase A, fructose-	Lyase, Schiff base, Glycolysis,	1835	5803
  		bisphosphate	Multigene family, 3D-structure,
  			Disease mutation
  NM_000045	ARG1	arginase, liver	Urea cycle, Arginine metabolism,	1836	5804
  			Hydrolase, Manganese, Disease
  			mutation, Polymorphism
  NM_000056	BCKDHB	branched chain keto	Oxidoreductase, Mitochondrion,	1837	5805
  		acid dehydrogenase	Transit peptide, Disease mutation,
  		E1, beta polypeptide	Maple syrup urine disease, 3D-
  		(maple syrup urine	structure
  		disease)
  NM_000070	CAPN3	calpain 3, (p94)	Hydrolase, Thiol protease, Calcium-	1838	5806
  			binding, Multigene family, Repeat,
  			Disease mutation, Polymorphism,
  			Alternative splicing
  NM_000073	CD3G	CD3G antigen,	Immunoglobulin domain, T-cell,	1839	5807
  		gamma polypeptide	Receptor, Transmembrane,
  		(TiT3 complex)	Glycoprotein, Signal
  NM_000074	TNFSF5	tumor necrosis factor	Cytokine, Transmembrane,	1840	5808
  		(ligand) superfamily,	Glycoprotein, Signal-anchor,
  		member 5 (hyper-	Antigen, Disease mutation,
  		IgM syndrome)	Polymorphism, 3D-structure
  NM_000081	CHS1	Chediak-Higashi	Protein transport, Transport, Repeat,	1841	5809
  		syndrome 1	WD repeat, Disease mutation,
  			Alternative splicing
  NM_000082	CKN1	Cockayne syndrome	Nuclear protein, Repeat, WD repeat,	1842	5810
  		1 (classical)	Transcription regulation,
  			Polymorphism, Cockayne's
  			syndrome, Deafness, Dwarfism
  NM_000095	COMP	cartilage oligomeric	Hypothetical protein, Glycoprotein,	1843	5811
  		matrix protein	Cell adhesion, Calcium-binding,
  		(pseudoachondroplasia,	Repeat, EGF-like domain, Signal,
  		epiphyseal	Disease mutation, Polymorphism
  		dysplasia 1, multiple)
  NM_000099	CST3	cystatin C (amyloid	Thiol protease inhibitor, Amyloid,	1844	5812
  		angiopathy and	Signal, Disease mutation,
  		cerebral	Polymorphism, 3D-structure
  		hemorrhage)
  NM_000100	CSTB	cystatin B (stefin B)	Thiol protease inhibitor, Nuclear	1845	5813
  			protein, Acetylation, Disease
  			mutation, Epilepsy, 3D-structure
  NM_000101	CYBA	cytochrome b-245,	Oxidoreductase, NADP, Electron	1846	5814
  		alpha polypeptide	transport, Membrane, Heme,
  			Polymorphism, Disease mutation,
  			Chronic granulomatous disease,
  			Hypothetical protein
  NM_000116	TAZ	tafazzin	Alternative splicing,	1847	5815
  		(cardiomyopathy,	Transmembrane, Disease mutation
  		dilated 3A (X-linked);
  		endocardial
  		fibroelastosis
  2;
  		Barth syndrome)
  NM_000120	EPHX1	epoxide hydrolase	1,	Hydrolase, Endoplasmic reticulum,	1848	5816
  		microsomal	Detoxification, Transmembrane,
  		(xenobiotic)	Aromatic hydrocarbons catabolism,
  			Microsome, Polymorphism
  NM_000121	EPOR	erythropoietin	Receptor, Transmembrane,	1849	5817
  		receptor	Glycoprotein, Signal,
  			Phosphorylation, 3D-structure
  NM_000126	ETFA	electron-transfer-	Electron transport, Flavoprotein,	1850	5818
  		flavoprotein, alpha	FAD, Mitochondrion, Transit peptide,
  		polypeptide (glutaric	Disease mutation, Glutaricaciduria,
  		aciduria II)	Polymorphism, 3D-structure
  NM_000130	F5	coagulation factor V	Blood coagulation, Glycoprotein,	1851	5819
  		(proaccelerin, labile	Sulfation, Calcium, Signal, Zymogen,
  		factor)	Repeat, Polymorphism, Disease
  			mutation, Thrombophilia, 3D-
  			structure
  NM_000143	FH	fumarate hydratase	Lyase, Tricarboxylic acid cycle,	1852	5820
  			Mitochondrion, Transit peptide,
  			Acetylation, Alternative initiation,
  			Anti-oncogene, Disease mutation
  NM_000146	FTL	ferritin, light	Hypothetical protein, Iron storage,	1853	5821
  		polypeptide	Metal-binding, Acetylation
  NM_000151	G6PC	glucose-6-	Glycogen biosynthesis, Hydrolase,	1854	5822
  		phosphatase,	Transmembrane, Glycoprotein,
  		catalytic (glycogen	Endoplasmic reticulum, Glycogen
  		storage disease type	storage disease, Disease mutation,
  		I, von Gierke	Polymorphism
  		disease)
  NM_000156	GAMT	guanidinoacetate N-	Transferase, Methyltransferase	1855	5823
  		methyltransferase
  NM_000157	GBA	glucosidase, beta;	Glycosidase, Hydrolase, Signal,	1856	5824
  		acid (includes	Hypothetical protein, Sphingolipid
  		glucosylceramidase)	metabolism, Glycoprotein,
  			Lysosome, Membrane, Gaucher
  			disease, Disease mutation,
  			Polymorphism, Alternative initiation,
  			Pharmaceutical
  NM_000175	GPI	glucose phosphate	Gluconeogenesis, Glycolysis,	1857	5825
  		isomerase	Isomerase, Growth factor, Cytokine,
  			Disease mutation, 3D-structure,
  			Hypothetical protein
  NM_000177	GSN	gelsolin	Cytoskeleton, Actin-binding, Repeat,	1858	5826
  		(amyloidosis, Finnish	Calcium, Alternative initiation,
  		type)	Signal, Amyloid, Disease mutation,
  			3D-structure, Phosphorylation, Actin
  			capping
  NM_000181	GUSB	glucuronidase, beta	Hydrolase, Glycosidase, Lysosome,	1859	5827
  			Glycoprotein, Signal,
  			Mucopolysaccharidosis, Disease
  			mutation, 3D-structure, Alternative
  			splicing, Polymorphism
  NM_000183	HADHB	hydroxyacyl-	Fatty acid metabolism, Transferase,	1860	5828
  		Coenzyme A	Acyltransferase, Mitochondrion,
  		dehydrogenase/3-	Transit peptide, Disease mutation,
  		ketoacyl-Coenzyme	Hypothetical protein
  		A thiolase/enoyl-
  		Coenzyme A
  		hydratase
  		(trifunctional
  		protein), beta
  		subunit
  NM_000186	HF1	H factor	1	Complement alternate pathway,	1861	5829
  		(complement)	Plasma, Glycoprotein, Repeat,
  			Sushi, Signal, 3D-structure,
  			Polymorphism, Alternative splicing
  NM_000206	IL2RG	interleukin 2	Receptor, Transmembrane,	1862	5830
  		receptor, gamma	Glycoprotein, Signal, Disease
  		(severe combined	mutation, SCID, 3D-structure
  		immunodeficiency)
  NM_000211	ITGB2	integrin,beta 2	Integrin, Cell adhesion, Receptor,	1863	5831
  		(antigen CD18 (p95),	Transmembrane, Glycoprotein,
  		lymphocyte function-	Repeat, Signal, Disease mutation,
  		associated antigen	Pyrrolidone carboxylic acid, 3D-
  		1; macrophage	structure
  		antigen 1 (mac-1)
  		beta subunit)
  NM_000229	LCAT	lecithin-cholesterol	Cholesterol metabolism, Lipid	1864	5832
  		acyltransferase	metabolism, Transferase,
  			Acyltransferase, Signal,
  			Glycoprotein, Polymorphism,
  			Disease mutation
  NM_000235	LIPA	lipase A, lysosomal	Hydrolase, Lipid degradation,	1865	5833
  		acid, cholesterol	Glycoprotein, Signal, Lysosome,
  		esterase (Wolman	Disease mutation, Polymorphism
  		disease)
  NM_000239	LYZ	lysozyme (renal	Hydrolase, Glycosidase,	1866	5834
  		amyloidosis)	Bacteriolytic enzyme, Signal,
  			Amyloid, 3D-structure, Disease
  			mutation, Polymorphism
  NM_000243	MEFV	Mediterranean fever	Inflammatory response, Actin-	1867	5835
  			binding, Metal-binding, Cytoskeleton,
  			Microtubule, Nuclear protein, Zinc-
  			finger, Zinc, Polymorphism, Disease
  			mutation, Alternative splicing
  NM_000249	MLH1	mutL homolog 1,	DNA repair, Nuclear protein,	1868	5836
  		colon cancer,	Disease mutation, Anti-oncogene,
  		nonpolyposis type 2	Polymorphism, Hereditary
  		(E. coli)	nonpolyposis colorectal cancer
  NM_000250	MPO	myeloperoxidase	Oxidoreductase, Peroxidase, Iron,	1869	5837
  			Heme, Calcium-binding,
  			Glycoprotein, Signal, Oxidation,
  			Lysosome, Alternative splicing,
  			Polymorphism, Disease mutation,
  			3D-structure
  NM_000254	MTR	5-	Transferase, Methyltransferase,	1870	5838
  		methyltetrahydrofolate-	Methionine biosynthesis, Vitamin
  		homocysteine	B12, Cobalt, Disease mutation,
  		methyltransferase	Polymorphism
  NM_000265	NCF1	neutrophil cytosolic	SH3 domain, Repeat,	1871	5839
  		factor 1 (47 kDa,	Polymorphism, Disease mutation,
  		chronic	Chronic granulomatous disease, 3D-
  		granulomatous	structure
  		disease, autosomal
  		1)
  NM_000269	NME1	non-metastatic cells	Transferase, Kinase, ATP-binding,	1872	5840
  		1, protein (NM23A)	Nuclear protein, Anti-oncogene,
  		expressed in	Disease mutation, 3D-structure
  NM_000270	NP	nucleoside	Hypothetical protein, Transferase,	1873	5841
  		phosphorylase	Glycosyltransferase, Polymorphism,
  			Disease mutation, 3D-structure
  NM_000285	PEPD	peptidase D	Collagen degradation, Hydrolase,	1874	5842
  			Dipeptidase, Metalloprotease,
  			Manganese, Acetylation,
  			Polymorphism, Disease mutation
  NM_000288	PEX7	peroxisomal	Repeat, WD repeat, Peroxisome,	1875	5843
  		biogenesis factor 7	Transport, Protein transport,
  			Rhizomelic chondrodysplasia
  			punctata, Disease mutation,
  			Polymorphism
  NM_000289	PFKM	phosphofructokinase,	Glycolysis, Kinase, Transferase,	1876	5844
  		muscle	Repeat, Allosteric enzyme,
  			Phosphorylation, Magnesium,
  			Multigene family, Alternative splicing,
  			Disease mutation, Glycogen storage
  			disease
  NM_000291	PGK1	phosphoglycerate	Transferase, Kinase, Multigene	1877	5845
  		kinase 1	family, Glycolysis, Acetylation,
  			Disease mutation, Polymorphism,
  			Hereditary hemolytic anemia
  NM_000295	SERPINA1	serine (or cysteine)	Serpin, Serine protease inhibitor,	1878	5846
  		proteinase inhibitor,	Glycoprotein, Plasma,
  		clade A (alpha-1	Polymorphism, Acute phase, Signal,
  		antiproteinase,	3D-structure, Disease mutation,
  		antitrypsin),member 1	Protease inhibitor
  NM_000297	PKD2	polycystic kidney	Ionic channel, Glycoprotein, Coiled	1879	5847
  		disease 2	coil, Transmembrane, Calcium-
  		(autosomal	binding, Disease mutation,
  		dominant)	Polymorphism
  NM_000302	PLOD	procollagen-lysine,	Oxidoreductase, Dioxygenase,	1880	5848
  		2-oxoglutarate 5-	Signal, Iron, Vitamin C, Glycoprotein,
  		dioxygenase (lysine	Endoplasmic reticulum, Membrane,
  		hydroxylase, Ehlers-	Polymorphism, Disease mutation,
  		Danlos syndrome	Ehlers-Danlos syndrome
  		type VI)
  NM_000305	PON2	paraoxonase 2	Hydrolase, Glycoprotein, Signal,	1881	5849
  			Membrane, Multigene family,
  			Polymorphism, Alternative splicing
  NM_000307	POU3F4	POU domain, class	Transcription regulation, Nuclear	1882	5850
  		3,transcription factor 4	protein, DNA-binding, Homeobox,
  			Disease mutation, Deafness
  NM_000320	QDPR	quinoid	Tetrahydrobiopterin biosynthesis,	1883	5851
  		dihydropteridine	Oxidoreductase, NADP, 3D-
  		reductase	structure, Polymorphism,
  			Phenylketonuria, Disease mutation
  NM_000321	RB1	retinoblastoma 1	Transcription regulation, DNA-	1884	5852
  		(including	binding, Nuclear protein,
  		osteosarcoma)	Phosphorylation, Anti-oncogene,
  			Disease mutation, 3D-structure
  NM_000327	ROM1	retinal outer	Vision, Cell adhesion,	1885	5853
  		segment membrane	Photoreceptor, Transmembrane,
  		protein 1	Polymorphism, Disease mutation,
  			Retinitis pigmentosa
  NM_000376	VDR	vitamin D (1,25-	Receptor, Transcription regulation,	1886	5854
  		dihydroxyvitamin D3)	DNA-binding, Nuclear protein, Zinc-
  		receptor	finger, Phosphorylation, Disease
  			mutation, 3D-structure
  NM_000377	WAS	Wiskott-Aldrich	Repeat, Disease mutation,	1887	5855
  		syndrome (eczema-	Phosphorylation, 3D-structure
  		thrombocytopenia)
  NM_000380	XPA	xeroderma	DNA repair, DNA-binding, Zinc-	1888	5856
  		pigmentosum,	finger, Nuclear protein, Xeroderma
  		complementation	pigmentosum, Disease mutation,
  		group A	Polymorphism, 3D-structure
  NM_000386	BLMH	bleomycin hydrolase	Hydrolase, Thiol protease,	1889	5857
  			Polymorphism, 3D-structure,
  			Hypothetical protein
  NM_000392	ABCC2	ATP-binding	ATP-binding, Glycoprotein,	1890	5858
  		cassette, sub-family	Transmembrane, Transport, Repeat,
  		C (CFTR/MRP),	Disease mutation, Polymorphism
  		member 2
  NM_000394	CRYAA	crystallin, alpha A	Eye lens protein, Acetylation,	1891	5859
  			Glycoprotein, Disease mutation,
  			Vision
  NM_000397	CYBB	cytochrome b-245,	Oxidoreductase, NADP, Electron	1892	5860
  		beta polypeptide	transport, Transmembrane, FAD,
  		(chronic	Heme, Glycoprotein, Voltage-gated
  		granulomatous	channel, Ionic channel, Disease
  		disease)	mutation, Chronic granulomatous
  			disease
  NM_000399	EGR2	early growth	Transcription regulation, Activator,	1893	5861
  		response 2 (Krox-20	DNA-binding, Nuclear protein,
  		homolog,	Repeat, Zinc-finger, Metal-binding,
  		Drosophila)	Alternative splicing, Disease
  			mutation, Charcot-Marie-Tooth
  			disease, Dejerine-Sottas syndrome
  NM_000401	EXT2	exostoses (multiple) 2	Transferase, Glycosyltransferase,	1894	5862
  			Endoplasmic reticulum, Golgi stack,
  			Transmembrane, Signal-anchor,
  			Glycoprotein, Anti-oncogene,
  			Disease mutation, Hereditary
  			multiple exostoses, Alternative
  			splicing
  NM_000402	G6PD	glucose-6-phosphate	Oxidoreductase, NADP, Glucose	1895	5863
  		dehydrogenase	metabolism, Disease mutation,
  			Polymorphism, Hereditary hemolytic
  			anemia, Alternative splicing,
  			Acetylation
  NM_000404	GLB1	galactosidase,beta 1	Hydrolase, Glycosidase, Lysosome,	1896	5864
  			Signal, Alternative splicing,
  			Glycoprotein, Polymorphism,
  			Disease mutation
  NM_000405	GM2A	GM2 ganglioside	Signal, Glycoprotein, Lysosome,	1897	5865
  		activator protein	Sphingolipid metabolism, GM2-
  			gangliosidosis, Disease mutation,
  			Polymorphism, 3D-structure
  NM_000407	GP1BB	glycoprotein Ib	Hypothetical protein, Cell division,	1898	5866
  		(platelet), beta	GTP-binding, Coiled coil, Platelet,
  		polypeptide	Transmembrane, Glycoprotein,
  			Hemostasis, Blood coagulation,
  			Signal, Phosphorylation, Cell
  			adhesion, Leucine-rich repeat
  NM_000418	IL4R	interleukin	4 receptor	Receptor, Transmembrane,	1899	5867
  			Glycoprotein, Signal, Disease
  			mutation, Polymorphism, 3D-
  			structure
  NM_000425	L1CAM	L1 cell adhesion	Neurogenesis, Cell adhesion,	1900	5868
  		molecule	Developmental protein,
  		(hydrocephalus,	Glycoprotein, Transmembrane,
  		stenosis of aqueduct	Repeat, Antigen, Immunoglobulin
  		of Sylvius 1, MASA	domain, Signal, Disease mutation,
  		(mental retardation,	Alternative splicing
  		aphasia, shuffling
  		gait and adducted
  		thumbs) syndrome,
  		spastic paraplegia 1)
  NM_000433	NCF2	neutrophil cytosolic	SH3 domain, Repeat, TPR repeat,	1901	5869
  		factor 2 (65 kDa,	Chronic granulomatous disease,
  		chronic	Disease mutation, 3D-structure
  		granulomatous
  		disease, autosomal
  		2)
  NM_000434	NEU1	sialidase 1	Hydrolase, Glycosidase, Signal,	1902	5870
  		(lysosomal sialidase)	Repeat, Glycoprotein, Disease
  			mutation, Polymorphism,
  			Phosphorylation
  NM_000436	OXCT	3-oxoacid CoA	Mitochondrion, Transferase, Transit	1903	5871
  		transferase	peptide, Disease mutation,
  			Polymorphism
  NM_000445	PLEC1	plectin	1,	Coiled coil, Repeat, Structural	1904	5872
  		intermediate filament	protein, Cytoskeleton, Actin-binding,
  		binding protein	Phosphorylation, Alternative splicing,
  		500 kDa	Epidermolysis bullosa, Disease
  			mutation
  NM_000454	SOD1	superoxide	Antioxidant, Oxidoreductase, Metal-	1905	5873
  		dismutase 1, soluble	binding, Copper, Zinc, Acetylation,
  		(amyotrophic lateral	3D-structure, Amyotrophic lateral
  		sclerosis 1 (adult))	sclerosis, Disease mutation
  NM_000456	SUOX	sulfite oxidase	Oxidoreductase, Mitochondrion,	1906	5874
  			Heme, Molybdenum, Transit peptide,
  			Disease mutation, 3D-structure
  NM_000462	UBE3A	ubiquitin protein	Ligase, Nuclear protein, Ubl	1907	5875
  		ligase E3A (human	conjugation pathway, Alternative
  		papilloma virus E6-	splicing, Disease mutation,
  		associated protein,	Polymorphism, 3D-structure,
  		Angelman	Hypothetical protein
  		syndrome)
  NM_000476	AK1	adenylate kinase 1	Transferase, Kinase, ATP-binding,	1908	5876
  			Acetylation, Disease mutation
  NM_000480	AMPD3	adenosine	Hydrolase, Nucleotide metabolism,	1909	5877
  		monophosphate	Multigene family, Polymorphism,
  		deaminase (isoform	Alternative splicing
  		E)
  NM_000481	AMT	aminomethyltransferase	Hypothetical protein, Transferase,	1910	5878
  		(glycine	Aminotransferase, Mitochondrion,
  		cleavage system	Transit peptide, Disease mutation
  		protein T)
  NM_000487	ARSA	arylsulfatase A	Hydrolase, Signal, Glycoprotein,	1911	5879
  			Lysosome, Disease mutation,
  			Metachromatic leukodystrophy,
  			Sphingolipid metabolism,
  			Polymorphism, 3D-structure
  NM_000497	CYP11B1	cytochrome P450,	Steroidogenesis, Electron transport,	1912	5880
  		family 11, subfamily	Steroid metabolism, Oxidoreductase,
  		B,polypeptide 1	Monooxygenase, Mitochondrion,
  			Membrane, Heme, Transit peptide,
  			Polymorphism, Disease mutation
  NM_000502	EPX	eosinophil	Oxidoreductase, Peroxidase, Iron,	1913	5881
  		peroxidase	Heme, Glycoprotein, Signal, Disease
  			mutation
  NM_000507	FBP1	fructose-1,6-	Hydrolase, Carbohydrate	1914	5882
  		bisphosphatase 1	metabolism, Gluconeogenesis, Zinc,
  			Allosteric enzyme, Disease mutation,
  			Polymorphism, 3D-structure,
  			Hypothetical protein
  NM_000512	GALNS	galactosamine (N-	Hypothetical protein	1915	5883
  		acetyl)-6-sulfate
  		sulfatase (Morquio
  		syndrome,
  		mucopolysaccharidosis
  		type IVA)
  NM_000517	HBA2	hemoglobin,alpha 2	Heme, Oxygen transport, Transport,	1916	5884
  			Erythrocyte, Disease mutation,
  			Polymorphism, Acetylation, 3D-
  			structure
  NM_000525	KCNJ11	potassium inwardly-	Ionic channel, Ion transport, Voltage-	1917	5885
  		rectifying channel,	gated channel, Transmembrane,
  		subfamily J, member	Potassium transport, Polymorphism,
  		11	Disease mutation, Diabetes mellitus
  NM_000528	MAN2B1	mannosidase, alpha,	Glycosidase, Hydrolase,	1918	5886
  		class 2B,member 1	Glycoprotein, Lysosome, Zymogen,
  			Signal, Disease mutation,
  			Polymorphism
  NM_000532	PCCB	propionyl Coenzyme	Hypothetical protein, Mitochondrion,	1919	5887
  		A carboxylase, beta	Transit peptide, Ligase, Disease
  		polypeptide	mutation
  NM_000542	SFTPB	surfactant,	Surface film, Gaseous exchange,	1920	5888
  		pulmonary-	Glycoprotein, Repeat,
  		associated protein B	Polymorphism, 3D-structure
  NM_000558	HBA1	hemoglobin,alpha 2	Heme, Oxygen transport, Transport,	1921	5889
  			Erythrocyte, Disease mutation,
  			Polymorphism, Acetylation, 3D-
  			structure
  NM_000565	IL6R	interleukin	6 receptor	Receptor, Transmembrane,	1922	5890
  			Glycoprotein, Immunoglobulin
  			domain, Repeat, Alternative splicing,
  			Signal, 3D-structure
  NM_000569	FCGR3A	Fc fragment of IgG,	IgG-binding protein, Receptor,	1923	5891
  		low affinity IIIa,	Transmembrane, Glycoprotein,
  		receptor for (CD16)	Signal, Immunoglobulin domain,
  			Repeat, Multigene family,
  			Polymorphism, GPI-anchor, 3D-
  			structure, Lipoprotein
  NM_000573	CR1	complement	Complement pathway, Glycoprotein,	1924	5892
  		component (3b/4b)	Transmembrane, Repeat, Signal,
  		receptor 1, including	Receptor, Sushi, Blood group
  		Knops blood group	antigen, Polymorphism, Pyrrolidone
  		system	carboxylic acid, 3D-structure
  NM_000578	SLC11A1	solute carrier family	Transport, Iron transport,	1925	5893
  		11 (proton-coupled	Transmembrane, Glycoprotein,
  		divalent metal ion	Macrophage, Polymorphism
  		transporters),
  		member 1
  NM_000581	GPX1	glutathione	Oxidoreductase, Peroxidase,	1926	5894
  		peroxidase 1	Selenium, Selenocysteine,
  			Erythrocyte, Polymorphism,
  			Hypothetical protein
  NM_000584	IL8	interleukin	8	Cytokine, Chemotaxis, Inflammatory	1927	5895
  			response, Signal, Alternative
  			splicing, 3D-structure
  NM_000591	CD14	CD14 antigen	Immune response, Inflammatory	1928	5896
  			response, Signal, GPI-anchor,
  			Repeat, Leucine-rich repeat,
  			Glycoprotein, Antigen, Lipoprotein
  NM_000607	ORM1	orosomucoid	1	Glycoprotein, Plasma, Acute phase,	1929	5897
  			Signal, Lipocalin, Polymorphism,
  			Multigene family, Pyrrolidone
  			carboxylic acid
  NM_000608	ORM2	orosomucoid 1	Glycoprotein, Plasma, Acute phase,	1930	5898
  			Signal, Lipocalin, Multigene family,
  			Polymorphism, Pyrrolidone
  			carboxylic acid
  NM_000631	NCF4	neutrophil cytosolic	SH3 domain, Alternative splicing,	1931	5899
  		factor 4, 40 kDa	3D-structure
  NM_000632	ITGAM	integrin, alpha M	Integrin, Cell adhesion, Receptor,	1932	5900
  		(complement	Glycoprotein, Transmembrane,
  		component receptor	Signal, 3D-structure, Repeat,
  		3, alpha; also known	Magnesium, Calcium
  		as CD11b (p170),
  		macrophage antigen
  		alpha polypeptide)
  NM_000633	BCL2	B-cell	Proto-oncogene, Apoptosis,	1933	5901
  		CLL/lymphoma 2	Alternative splicing,
  			Transmembrane, Mitochondrion,
  			Phosphorylation, Chromosomal
  			translocation, Polymorphism,
  			Disease mutation, 3D-structure
  NM_000634	IL8RA	interleukin 8	G-protein coupled receptor,	1934	5902
  		receptor, alpha	Transmembrane, Glycoprotein,
  			Chemotaxis, Polymorphism, 3D-
  			structure, Receptor
  NM_000651	CR1	complement	Complement pathway, Glycoprotein,	1935	5903
  		component (3b/4b)	Transmembrane, Repeat, Signal,
  		receptor 1, including	Receptor, Sushi, Blood group
  		Knops blood group	antigen, Polymorphism, Pyrrolidone
  		system	carboxylic acid, 3D-structure
  NM_000655	SELL	selectin L	EGF-like domain, Cell adhesion,	1936	5904
  		(lymphocyte	Transmembrane, Glycoprotein,
  		adhesion molecule	Lectin, Selectin, Signal, Sushi,
  		1)	Repeat, 3D-structure
  NM_000671	ADH5	alcohol	Oxidoreductase, Zinc, Metal-binding,	1937	5905
  		dehydrogenase 5	NAD, Multigene family, Acetylation,
  		(class III), chi	3D-structure
  		polypeptide
  NM_000675	ADORA2A	adenosine A2a	G-protein coupled receptor,	1938	5906
  		receptor	Transmembrane, Glycoprotein, 3D-
  			structure, Polymorphism
  NM_000688	ALAS1	aminolevulinate,	Heme biosynthesis, Transferase,	1939	5907
  		delta-,synthase 1	Acyltransferase, Mitochondrion,
  			Transit peptide, Pyridoxal
  			phosphate, Multigene family
  NM_000690	ALDH2	aldehyde	Oxidoreductase, NAD,	1940	5908
  		dehydrogenase 2	Mitochondrion, Transit peptide,
  		family	Polymorphism, 3D-structure
  		(mitochondrial)
  NM_000694	ALDH3B1	aldehyde	Oxidoreductase, NAD	1941	5909
  		dehydrogenase 3
  		family, member B1
  NM_000698	ALOX5	arachidonate 5-	Oxidoreductase, Dioxygenase, Iron,	1942	5910
  		lipoxygenase	Leukotriene biosynthesis, Calcium
  NM_000701	ATP1A1	ATPase, Na+/K+	Hydrolase, Sodium/potassium	1943	5911
  		transporting,alpha 1	transport, Transmembrane,
  		polypeptide	Phosphorylation, Magnesium, Metal-
  			binding, ATP-binding, Multigene
  			family, Alternative splicing
  NM_000712	BLVRA	biliverdin reductase A	Oxidoreductase, NAD, NADP, Zinc,	1944	5912
  			Polymorphism
  NM_000714	BZRP	benzodiazapine	Mitochondrion, Receptor,	1945	5913
  		receptor (peripheral)	Transmembrane, Polymorphism
  NM_000717	CA4	carbonic anhydrase	GPI-anchor, Membrane, Lyase, Zinc,	1946	5914
  		IV	Signal, 3D-structure, Lipoprotein
  NM_000718	CACNA1B	calcium channel,	Ionic channel, Transmembrane, Ion	1947	5915
  		voltage-dependent,	transport, Voltage-gated channel,
  		L type, alpha 1B	Calcium channel, Glycoprotein,
  		subunit	Repeat, Multigene family, Calcium-
  			binding, Phosphorylation, ATP-
  			binding, Alternative splicing
  NM_000732	CD3D	CD3D antigen, delta	Immunoglobulin domain, T-cell,	1948	5916
  		polypeptide (TiT3	Receptor, Transmembrane,
  		complex)	Glycoprotein, Signal
  NM_000734	CD3Z	CD3Z antigen, zeta	T-cell, Receptor, Transmembrane,	1949	5917
  		polypeptide (TiT3	Signal, Repeat, Alternative splicing,
  		complex)	Phosphorylation, 3D-structure
  NM_000748	CHRNB2	cholinergic receptor,	Postsynaptic membrane, Ionic	1950	5918
  		nicotinic, beta	channel, Glycoprotein, Signal,
  		polypeptide 2	Transmembrane, Multigene family,
  		(neuronal)	Disease mutation, Epilepsy
  NM_000749	CHRNB3	cholinergic receptor,	Postsynaptic membrane, Ionic	1951	5919
  		nicotinic, beta	channel, Glycoprotein, Signal,
  		polypeptide 3	Transmembrane, Multigene family
  NM_000752	LTB4R	leukotriene B4	Apoptosis, 3D-structure, RNA-	1952	5920
  		receptor 2	binding, Repeat, G-protein coupled
  			receptor, Transmembrane,
  			Glycoprotein
  NM_000757	CSF1	colony stimulating	Cytokine, Growth factor,	1953	5921
  		factor 1	Glycoprotein, Proteoglycan,
  		(macrophage)	Transmembrane, Signal, Alternative
  			splicing, 3D-structure
  NM_000760	CSF3R	colony stimulating	Cell adhesion, Receptor, Repeat,	1954	5922
  		factor 3 receptor	Signal, Transmembrane,
  		(granulocyte)	Immunoglobulin domain,
  			Glycoprotein, Alternative splicing,
  			Polymorphism, 3D-structure
  NM_000778	CYP4A11	cytochrome P450,	Heme, Monooxygenase,	1955	5923
  		family 4, subfamily	Oxidoreductase, Electron transport,
  		A, polypeptide 11	Membrane, Microsome,
  			Endoplasmic reticulum,
  			Polymorphism
  NM_000801	FKBP1A	FK506 binding	Isomerase, Rotamase, 3D-structure	1956	5924
  		protein 1A, 12 kDa
  NM_000804	FOLR3	folate receptor	3	Receptor, Glycoprotein, Signal,	1957	5925
  		(gamma)	Folate-binding, Multigene family,
  			Alternative splicing
  NM_000819	GART	phosphoribosylglycin	Multifunctional enzyme, Purine	1958	5926
  		amide	biosynthesis, Ligase, Transferase,
  		formyltransferase,	Alternative splicing, Polymorphism
  		phosphoribosylglycin
  		amide synthetase,
  		phosphoribosylaminoimidazole
  		synthetase
  NM_000846	GSTA2	glutathione S-	Transferase, Multigene family,	1959	5927
  		transferase A2	Polymorphism, 3D-structure
  NM_000856	GUCY1A3	guanylate cyclase	1,	Lyase, cGMP biosynthesis,	1960	5928
  		soluble,alpha 3	Multigene family
  NM_000857	GUCY1B3	guanylate cyclase 1,	Lyase, cGMP biosynthesis,	1961	5929
  		soluble,beta 3	Alternative splicing
  NM_000871	HTR6	5-hydroxytryptamine	G-protein coupled receptor,	1962	5930
  		(serotonin)receptor 6	Transmembrane, Glycoprotein,
  			Multigene family
  NM_000876	IGF2R	insulin-like growth	Transmembrane, Transport,	1963	5931
  		factor 2 receptor	Glycoprotein, Repeat, Receptor,
  			Lysosome, Signal, Polymorphism,
  			3D-structure
  NM_000877	IL1R1	interleukin	1	Receptor, Repeat, Signal,	1964	5932
  		receptor, type I	Transmembrane, Immunoglobulin
  			domain, Glycoprotein,
  			Phosphorylation, 3D-structure
  NM_000878	IL2RB	interleukin	2	Receptor, Transmembrane,	1965	5933
  		receptor, beta	Glycoprotein, Signal, 3D-structure
  NM_000883	IMPDH1	IMP (inosine	Oxidoreductase, NAD, GMP	1966	5934
  		monophosphate)	biosynthesis, Purine biosynthesis,
  		dehydrogenase 1	Multigene family, Repeat, CBS
  			domain, Alternative splicing, Vision,
  			Retinitis pigmentosa, Disease
  			mutation
  NM_000895	LTA4H	leukotriene A4	Multifunctional enzyme, Hydrolase,	1967	5935
  		hydrolase	Leukotriene biosynthesis,
  			Metalloprotease, Metal-binding, Zinc,
  			3D-structure
  NM_000903	NQO1	NAD(P)H	Oxidoreductase, NAD, NADP,	1968	5936
  		dehydrogenase,	Flavoprotein, FAD, Multigene family,
  		quinone 1	Polymorphism, 3D-structure
  NM_000904	NQO2	NAD(P)H	Oxidoreductase, Flavoprotein, FAD,	1969	5937
  		dehydrogenase,	Multigene family, Zinc, 3D-structure
  		quinone
  2
  NM_000918	P4HB	procollagen-proline,	Redox-active center, Isomerase,	1970	5938
  		2-oxoglutarate 4-	Endoplasmic reticulum, Repeat,
  		dioxygenase (proline	Signal, 3D-structure, Hypothetical
  		4-hydroxylase), beta	protein
  		polypeptide (protein
  		disulfide isomerase;
  		thyroid hormone
  		binding protein p55)
  NM_000952	PTAFR	platelet-activating	G-protein coupled receptor,	1971	5939
  		factor receptor	Transmembrane, Glycoprotein,
  			Chemotaxis, Polymorphism,
  			Hypothetical protein
  NM_000954	PTGDS	prostaglandin D2	Isomerase, Prostaglandin	1972	5940
  		synthase 21 kDa	biosynthesis, Transport,
  		(brain)	Glycoprotein, Signal, Membrane,
  			Lipocalin, Polymorphism
  NM_000963	PTGS2	prostaglandin-	Oxidoreductase, Dioxygenase,	1973	5941
  		endoperoxide	Peroxidase, Glycoprotein,
  		synthase 2	Prostaglandin biosynthesis, Heme,
  		(prostaglandin G/H	Iron, Signal, Membrane,
  		synthase and	Polymorphism
  		cyclooxygenase)
  NM_000966	RARG	retinoic acid	Receptor, Transcription regulation,	1974	5942
  		receptor, gamma	DNA-binding, Nuclear protein, Zinc-
  			finger, Multigene family, Alternative
  			splicing, 3D-structure
  NM_000969	RPL5	ribosomal protein L5	Ribosomal protein, rRNA-binding,	1975	5943
  			Hydrolase, Metalloprotease,
  			Aminopeptidase, Zinc, Nuclear
  			protein
  NM_000985	RPL17	ribosomal protein	Hypothetical protein, Ribosomal	1976	5944
  		L17	protein
  NM_000992	RPL29	ribosomal protein	Methylation, Ribosomal protein,	1977	5945
  		L29	Repeat, Heparin-binding
  NM_000995	RPL34	ribosomal protein	Ribosomal protein	1978	5946
  		L34
  NM_001006	RPS3A	ribosomal protein	Ribosomal protein	1979	5947
  		S3A
  NM_001017	RPS13	ribosomal protein	Ribosomal protein	1980	5948
  		S13
  NM_001048	SST	somatostatin	Cleavage on pair of basic residues,	1981	5949
  			Hormone, Signal, Pharmaceutical
  NM_001051	SSTR3	somatostatin	G-protein coupled receptor,	1982	5950
  		receptor 3	Transmembrane, Glycoprotein,
  			Multigene family, Polymorphism
  NM_001052	SSTR4	somatostatin	G-protein coupled receptor,	1983	5951
  		receptor 4	Transmembrane, Glycoprotein,
  			Multigene family, Lipoprotein,
  			Palmitate, Phosphorylation,
  			Polymorphism
  NM_001054	SULT1A2	sulfotransferase	Transferase, Steroid metabolism,	1984	5952
  		family, cytosolic, 1A,	Polymorphism
  		phenol-preferring,
  		member 2
  NM_001055	SULT1A1	sulfotransferase	Transferase, Catecholamine	1985	5953
  		family, cytosolic, 1A,	metabolism, Steroid metabolism,
  		phenol-preferring,	Polymorphism
  		member 1
  NM_001060	TBXA2R	thromboxane A2	G-protein coupled receptor,	1986	5954
  		receptor	Transmembrane, Glycoprotein,
  			Disease mutation, Alternative
  			splicing, Polymorphism, 3D-
  			structure, Hypothetical protein,
  			Metal-binding, Nuclear protein, Zinc,
  			Zinc-finger
  NM_001062	TCN1	transcobalamin I	Transport, Cobalt transport,	1987	5955
  		(vitamin B12 binding	Glycoprotein, Signal
  		protein, R binder
  		family)
  NM_001064	TKT	transketolase	Transferase, Thiamine	1988	5956
  		(Wernicke-Korsakoff	pyrophosphate, Calcium-binding
  		syndrome)
  NM_001065	TNFRSF1A	tumor necrosis factor	Receptor, Apoptosis,	1989	5957
  		receptor superfamily,	Transmembrane, Glycoprotein,
  		member 1A	Repeat, Signal, Disease mutation,
  			Polymorphism, 3D-structure
  NM_001066	TNFRSF1B	tumor necrosis factor	Receptor, Apoptosis,	1990	5958
  		receptor superfamily,	Transmembrane, Glycoprotein,
  		member 1B	Repeat, Signal, Phosphorylation,
  			Pharmaceutical, Polymorphism, 3D-
  			structure
  NM_001082	CYP4F2	cytochrome P450,	Heme, Monooxygenase,	1991	5959
  		family 4, subfamily	Oxidoreductase, Electron transport,
  		F,polypeptide 2	Membrane, Microsome,
  			Endoplasmic reticulum,
  			Polymorphism, NADP
  NM_001087	AAMP	angio-associated,	Repeat, WD repeat	1992	5960
  		migratory cell protein
  NM_001089	ABCA3	ATP-binding	ATP-binding, Transport,	1993	5961
  		cassette, sub-family	Transmembrane
  		A (ABC1),member 3
  NM_001090	ABCF1	ATP-binding	ATP-binding	1994	5962
  		cassette, sub-family
  		F (GCN20),member 1
  NM_001091	ABP1	amiloride binding	Signal, Glycoprotein,	1995	5963
  		protein 1 (amine	Oxidoreductase, Copper, Heparin-
  		oxidase (copper-	binding, TPQ, Alternative splicing,
  		containing))	Polymorphism, Metal-binding
  NM_001099	ACPP	acid phosphatase,	Hydrolase, Glycoprotein, Signal, 3D-	1996	5964
  		prostate	structure
  NM_001101	ACTB	actin, beta	Hypothetical protein, Structural	1997	5965
  			protein, Multigene family,
  			Methylation, Acetylation,
  			Cytoskeleton, 3D-structure
  NM_001102	ACTN1	actinin,alpha 1	Cytoskeleton, Actin-binding,	1998	5966
  			Calcium-binding, Repeat, Multigene
  			family, Phosphorylation
  NM_001105	ACVR1	activin A receptor,	Receptor, Transferase,	1999	5967
  		type I	Serine/threonine-protein kinase,
  			ATP-binding, Transmembrane,
  			Glycoprotein, Signal
  NM_001107	ACYP1	acylphosphatase 1,	Hydrolase, Acetylation,Multigene	2000	5968
  		erythrocyte	family
  		(common) type
  NM_001109	ADAM8	a disintegrin and	Hydrolase, Metalloprotease, Zinc,	2001	5969
  		metalloproteinase	Signal, Glycoprotein,
  		domain 8	Transmembrane, Antigen, EGF-like
  			domain
  NM_001120	TETRAN	tetracycline	Transmembrane	2002	5970
  		transporter-like
  		protein
  NM_001129	AEBP1	AE binding protein 1	Carboxypeptidase	2003	5971
  NM_001140	ALOX15	arachidonate 15-	Oxidoreductase, Dioxygenase, Iron,	2004	5972
  		lipoxygenase	Leukotriene biosynthesis
  NM_001150	ANPEP	alanyl (membrane)	Angiogenesis, Hydrolase,	2005	5973
  		aminopeptidase	Aminopeptidase, Metalloprotease,
  		(aminopeptidase N,	Zinc, Signal-anchor,
  		aminopeptidase M,	Transmembrane, Glycoprotein,
  		microsomal	Sulfation, Polymorphism
  		aminopeptidase,
  		CD13, p150)
  NM_001152	SLC25A5	solute carrier family	Mitochondrion, Inner membrane,	2006	5974
  		25 (mitochondrial	Repeat, Transmembrane, Transport,
  		carrier; adenine	Multigene family
  		nucleotide
  		translocator),
  		member 5
  NM_001153	ANXA4	annexin A4	Annexin, Calcium/phospholipid-	2007	5975
  			binding, Repeat
  NM_001155	ANXA6	annexin A6	Annexin, Calcium/phospholipid-	2008	5976
  			binding, Repeat, Acetylation,
  			Phosphorylation, 3D-structure
  NM_001157	ANXA11	annexin A11	Annexin, Calcium/phospholipid-	2009	5977
  			binding, Repeat, Polymorphism
  NM_001172	ARG2	arginase, type II	Urea cycle, Arginine metabolism,	2010	5978
  			Hydrolase, Manganese, Transit
  			peptide, Mitochondrion, Receptor,
  			Transmembrane, Transport, Protein
  			transport, Coiled coil, Alternative
  			splicing
  NM_001175	ARHGDIB	Rho GDP	GTPase activation, 3D-structure	2011	5979
  		dissociation inhibitor
  		(GDI) beta
  NM_001181	ASGR2	asialoglycoprotein	Lectin, Glycoprotein, Receptor,	2012	5980
  		receptor 2	Endocytosis, Transmembrane,
  			Calcium, Signal-anchor,
  			Phosphorylation, Alternative splicing
  NM_001182	ALDH7A1	aldehyde	Oxidoreductase, NAD	2013	5981
  		dehydrogenase 7
  		family, member A1
  NM_001183	ATP6IP1	ATPase, H+	Hypothetical protein, ATP synthesis,	2014	5982
  		transporting,	Hydrogen ion transport, Hydrolase,
  		lysosomal accessory	ATP-binding, Transmembrane,
  		protein 1	Glycoprotein, Signal
  NM_001184	ATR	ataxia telangiectasia	Kinase, Transferase	2015	5983
  		and Rad3 related
  NM_001196	BID	BH3 interacting	Apoptosis, 3D-structure	2016	5984
  		domain death
  		agonist
  NM_001199	BMP1	bone morphogenetic	Growth factor, Cytokine, Repeat,	2017	5985
  		protein 1	Osteogenesis, Chondrogenesis,
  			Hydrolase, Metalloprotease, EGF-
  			like domain, Zinc, Calcium, Signal,
  			Glycoprotein, Zymogen, Alternative
  			splicing, Collagen
  NM_001206	BTEB1	basic transcription	Transcription regulation, DNA-	2018	5986
  		element binding	binding, Nuclear protein, Repeat,
  		protein 1	Zinc-finger, Metal-binding
  NM_001207	BTF3	basic transcription	Transcription regulation, Nuclear	2019	5987
  		factor 3	protein, Alternative splicing
  NM_001208	BTF3L1	basic transcription	Transcription regulation, Nuclear	2020	5988
  		factor 3, like 1	protein
  NM_001212	C1QBP	complement	Mitochondrion, Transit peptide, 3D-	2021	5989
  		component 1, q	structure, Hypothetical protein
  		subcomponent
  		binding protein
  NM_001222	CAMK2G	calcium/calmodulin-	Alternative splicing	2022	5990
  		dependent protein
  		kinase (CaM kinase)
  		II gamma
  NM_001237	CCNA2	cyclin A2	Cyclin, Cell cycle, Cell division,	2023	5991
  			Mitosis, 3D-structure
  NM_001252	TNFSF7	tumor necrosis factor	Cytokine, Transmembrane,	2024	5992
  		(ligand) superfamily,	Glycoprotein, Signal-anchor, Antigen
  		member 7
  NM_001256	CDC27	cell division cycle 27	Repeat, TPR repeat, Nuclear	2025	5993
  			protein, Polymorphism
  NM_001259	CDK6	cyclin-dependent	Transferase, Serine/threonine-	2026	5994
  		kinase 6	protein kinase, ATP-binding, Cell
  			cycle, Cell division, Phosphorylation,
  			3D-structure
  NM_001266	CES1	carboxylesterase	1	Glycoprotein, Hydrolase, Serine	2027	5995
  		(monocyte/macrophage	esterase, Endoplasmic reticulum,
  		serine esterase	Signal, Multigene family,
  		1)	Polymorphism, Hypothetical protein
  NM_001276	CHI3L1	chitinase 3-like 1	Glycoprotein, Signal, 3D-structure	2028	5996
  		(cartilage
  		glycoprotein-39)
  NM_001282	AP2B1	adaptor-related	Hypothetical protein, Coated pits,	2029	5997
  		protein complex 2,	3D-structure
  		beta
  1 subunit
  NM_001284	AP3S1	adaptor-related	Golgi stack, Protein transport,	2030	5998
  		protein complex 3,	Transport
  		sigma 1 subunit
  NM_001286	CLCN6	chloride channel 6	Ionic channel, Ion transport, Chloride	2031	5999
  			channel, Chloride, Voltage-gated
  			channel, Transmembrane, CBS
  			domain, Repeat, Alternative splicing
  NM_001288	CLIC1	chloride intracellular	Ionic channel, Ion transport, Chloride	2032	6000
  		channel 1	channel, Chloride, Voltage-gated
  			channel, Nuclear protein, 3D-
  			structure
  NM_001292	CLK3	CDC-like kinase 3	Transferase, Serine/threonine-	2033	6001
  			protein kinase, ATP-binding,
  			Tyrosine-protein kinase,
  			Phosphorylation, Nuclear protein,
  			Alternative splicing
  NM_001293	CLNS1A	chloride channel,	Nuclear protein, Polymorphism	2034	6002
  		nucleotide-sensitive,
  		1A
  NM_001294	CLPTM1	cleft lip and palate	Transmembrane	2035	6003
  		associated
  		transmembrane
  		protein
  1
  NM_001305	CLDN4	claudin 4	Tight junction, Transmembrane,	2036	6004
  			Williams-Beuren syndrome
  NM_001313	CRMP1	collapsin response	Repeat, WD repeat	2037	6005
  		mediator protein 1
  NM_001315	MAPK14	mitogen-activated	ATP-binding, Kinase, Transferase,	2038	6006
  		protein kinase 14	Serine/threonine-protein kinase,
  			Phosphorylation, Alternative splicing,
  			3D-structure
  NM_001317	CSH1	chorionic	Chorion, Hormone, Placenta,	2039	6007
  		somatomammotropin	Multigene family, Signal
  		hormone 1
  		(placental lactogen)
  NM_001325	CSTF2	cleavage stimulation	RNA-binding, Repeat,	2040	6008
  		factor, 3′ pre-RNA,	Phosphorylation,Nuclear protein
  		subunit
  2, 64 kDa
  NM_001331	CTNND1	catenin (cadherin-	Cytoskeleton, Structural protein,	2041	6009
  		associated protein),	Phosphorylation, Repeat,Cell
  		delta
  1	adhesion, Coiled coil, Nuclear
  			protein, Alternative splicing
  NM_001338	CXADR	coxsackie virus and	Immunoglobulin domain, Receptor,	2042	6010
  		adenovirus receptor	Transmembrane, Glycoprotein,
  			Signal, Repeat, 3D-structure
  NM_001346	DGKG	diacylglycerol	Transferase, Kinase, Calcium-	2043	6011
  		kinase, gamma	binding, Phorbol-ester binding,
  		90 kDa	Repeat, Multigene family, Alternative
  			splicing
  NM_001357	DDX9	DEAH (Asp-Glu-Ala-	Helicase, RNA-binding, DNA-	2044	6012
  		His)box polypeptide 9	binding, Repeat, Nuclear protein,
  			ATP-binding
  NM_001358	DDX15	DEAH (Asp-Glu-Ala-	mRNA processing, mRNA splicing,	2045	6013
  		His) box polypeptide	Helicase, ATP-binding, Nuclear
  		15	protein
  NM_001363	DKC1	dyskeratosis	Telomere, RNA-binding, Nuclear	2046	6014
  		congenita 1,	protein, Disease mutation
  		dyskerin
  NM_001381	DOK1	docking protein	1,	Phosphorylation, Alternative splicing	2047	6015
  		62 kDa (downstream
  		of tyrosine kinase 1)
  NM_001383	DPH2L1	diptheria toxin		2048	6016
  		resistance protein
  		required for
  		diphthamide
  		biosynthesis-like 1
  		(S. cerevisiae)
  NM_001388	DRG2	developmentally	GTP-binding	2049	6017
  		regulatedGTP
  		binding protein
  2
  NM_001406	EFNB3	ephrin-B3	Developmental protein,	2050	6018
  			Neurogenesis, Transmembrane,
  			Glycoprotein, Signal, Polymorphism
  NM_001415	EIF2S3	eukaryotic	Initiation factor, Protein biosynthesis,	2051	6019
  		translation initiation	GTP-binding, Polymorphism
  		factor 2,subunit 3
  		gamma, 52 kDa
  NM_001419	ELAVL1	ELAV (embryonic	RNA-binding, Repeat	2052	6020
  		lethal, abnormal
  		vision,Drosophila)-
  		like 1 (Hu antigen R)
  NM_001421	ELF4	E74-like factor 4 (ets		2053	6021
  		domain transcription
  		factor)
  NM_001423	EMP1	epithelial membrane	Transmembrane, Glycoprotein	2054	6022
  		protein 1
  NM_001431	EPB41L2	erythrocyte	Hypothetical protein, Structural	2055	6023
  		membrane protein	protein, Cytoskeleton, Actin-binding
  		band 4.1-like 2
  NM_001432	EREG	epiregulin	Angiogenesis, Growth factor,	2056	6024
  			Mitogen, Glycoprotein, EGF-like
  			domain, Transmembrane, Signal
  NM_001440	EXTL3	exostoses (multiple)-	Transferase, Glycosyltransferase,	2057	6025
  		like 3	Endoplasmic reticulum,
  			Transmembrane, Signal-anchor,
  			Glycoprotein
  NM_001444	FABP5	fatty acid binding	Transport, Lipid-binding, 3D-	2058	6026
  		protein 5 (psoriasis-	structure
  		associated)
  NM_001449	FHL1	four and a half LIM	Coiled coil, Transcription regulation,	2059	6027
  		domains 1	Nuclear protein, Disease mutation,
  			Anhidrotic ectodermal dysplasia,
  			Repeat, LIM domain, Metal-binding,
  			Zinc, Developmental protein,
  			Differentiation, Zinc-finger
  NM_001455	FOXO3A	forkhead box O3A	Transcription regulation, DNA-	2060	6028
  			binding, Nuclear protein, Apoptosis,
  			Chromosomal translocation, Proto-
  			oncogene, Phosphorylation
  NM_001456	FLNA	filamin A, alpha	Cytoskeleton, Actin-binding, Repeat,	2061	6029
  		(actin binding protein	Phosphorylation, Polymorphism,
  		280)	Disease mutation, Multigene family,
  			Hypothetical protein
  NM_001462	FPRL1	formyl peptide	G-protein coupled receptor,	2062	6030
  		receptor-like 1	Transmembrane, Glycoprotein,
  			Chemotaxis, Repeat, WD repeat
  NM_001465	FYB	FYN binding protein	SH3 domain, Phosphorylation,	2063	6031
  		(FYB-120/130)	Nuclear protein, Coiled coil,
  			Alternative splicing
  NM_001467	G6PT1	solute carrier family	Transmembrane, Transport, Sugar	2064	6032
  		37 (glycerol-6-	transport, Endoplasmic reticulum,
  		phosphate	Alternative splicing, Glycogen
  		transporter),	storage disease,Disease mutation
  		member
  4
  NM_001469	G22P1	thyroid autoantigen	Helicase, Nuclear protein, DNA-	2065	6033
  		70 kDa (Ku antigen)	binding, Phosphorylation, Antigen,
  			Systemic lupus erythematosus,
  			Acetylation, 3D-structure
  NM_001478	GALGT	UDP-N-acetyl-alpha-	Hypothetical protein, Transferase,	2066	6034
  		D-galactosamine:(N-	Glycosyltransferase,
  		acetylneuraminyl)-	Transmembrane, Signal-anchor,
  		galactosylglucosylceramide	Golgi stack, Glycoprotein,
  		N-	Polymorphism
  		acetylgalactosaminyl
  		transferase
  		(GalNAc-T)
  NM_001482	GATM	glycine	Transferase, Mitochondrion, Transit	2067	6035
  		amidinotransferase	peptide, 3D-structure, Alternative
  		(L-arginine:glycine	splicing
  		amidinotransferase)
  NM_001483	GBAS	glioblastoma		2068	6036
  		amplified sequence
  NM_001487	GCN5L1	GCN5 general		2069	6037
  		control of amino-acid
  		synthesis 5-like 1
  		(yeast)
  NM_001493	GDI1	GDP dissociation	GTPase activation, Disease	2070	6038
  		inhibitor 1	mutation
  NM_001500	GMDS	GDP-mannose 4,6-	Lyase, NADP	2071	6039
  		dehydratase
  NM_001503	GPLD1	glycosylphosphatidyl	Hydrolase, Glycoprotein, Signal,	2072	6040
  		inositol specific	Hypothetical protein
  		phospholipase D1
  NM_001504	CXCR3	chemokine (C—X—C	G-protein coupled receptor,	2073	6041
  		motif)receptor 3	Transmembrane, Glycoprotein,
  			Antigen, Polymorphism
  NM_001517	GTF2H4	general transcription	Transcription regulation, DNA repair,	2074	6042
  		factor IIH,	Nuclear protein
  		polypeptide
  4,
  		52 kDa
  NM_001518	GTF2I	general transcription	Transcription regulation, DNA-	2075	6043
  		factor II, i	binding, Nuclear protein,
  			Phosphorylation, Repeat, Williams-
  			Beuren syndrome, Alternative
  			splicing
  NM_001519	BRF1	BRF1 homolog,	Transcription regulation, Activator,	2076	6044
  		subunit of RNA	Nuclear protein, Repeat, Zinc-finger,
  		polymerase III	Metal-binding, Zinc, Alternative
  		transcription	splicing, Hypothetical protein
  		initiation factor IIIB
  		(S. cerevisiae)
  NM_001520	GTF3C1	general transcription		2077	6045
  		factor IIIC,
  		polypeptide 1, alpha
  		220 kDa
  NM_001528	HGFAC	HGF activator	Hydrolase, Glycoprotein, Plasma,	2078	6046
  			Serine protease, Kringle, Signal,
  			EGF-like domain, Repeat, Zymogen
  NM_001531	MR1	major	MHC, Glycoprotein, Transmembrane	2079	6047
  		histocompatibility
  		complex, class I-
  		related
  NM_001536	HRMT1L2	HMT1 hnRNP	Transferase, Methyltransferase,	2080	6048
  		methyltransferase-	Nuclear protein, Alternative splicing
  		like 2 (S. cerevisiae)
  NM_001538	HSF4	F-box and leucine-	Transcription regulation, Nuclear	2081	6049
  		rich repeat protein 8	protein, DNA-binding, Activator,
  			Repressor, Heat shock, Multigene
  			family, Alternative splicing
  NM_001539	DNAJA1	DnaJ (Hsp40)	Chaperone, Repeat, Zinc, Metal-	2082	6050
  		homolog, subfamily	binding, Prenylation, Lipoprotein,
  		A,member 1	Multigene family
  NM_001550	IFRD1	interferon-related		2083	6051
  		developmental
  		regulator
  1
  NM_001551	IGBP1	immunoglobulin	B-cell activation, Phosphorylation	2084	6052
  		(CD79A) binding
  		protein 1
  NM_001554	CYR61	cysteine-rich,	Plasmid, Chemotaxis, Cell adhesion,	2085	6053
  		angiogenic inducer,	Growth factor binding, Heparin-
  		61	binding, Signal
  NM_001557	IL8RB	interleukin 8	G-protein coupled receptor,	2086	6054
  		receptor, beta	Transmembrane, Glycoprotein,
  			Chemotaxis, Polymorphism,
  			Receptor
  NM_001558	IL10RA	interleukin 10	Receptor, Transmembrane,	2087	6055
  		receptor, alpha	Glycoprotein, Signal, Polymorphism,
  			3D-structure
  NM_001567	INPPL1	inositol	DNA repair	2088	6056
  		polyphosphate
  		phosphatase-like 1
  NM_001572	IRF7	interferon regulatory	Transcription regulation, DNA-	2089	6057
  		factor 7	binding, Nuclear protein, Activator,
  			Alternative splicing, Collagen
  NM_001607	ACAA1	acetyl-Coenzyme A	Acyltransferase, Transferase, Fatty	2090	6058
  		acyltransferase 1	acid metabolism, Peroxisome,
  		(peroxisomal 3-	Transit peptide, Polymorphism
  		oxoacyl-Coenzyme
  		A thiolase)
  NM_001618	ADPRT	ADP-	Transferase, Glycosyltransferase,	2091	6059
  		ribosyltransferase	NAD, DNA-binding, Nuclear protein,
  		(NAD+; poly (ADP-	ADP-ribosylation, Zinc-finger, Zinc,
  		ribose) polymerase)	Polymorphism
  NM_001619	ADRBK1	adrenergic, beta,	Kinase, Receptor, Transferase,	2092	6060
  		receptor kinase 1	Serine/threonine-protein kinase,
  			ATP-binding, Multigene family, 3D-
  			structure
  NM_001621	AHR	aryl hydrocarbon	Cell cycle, Transcription regulation,	2093	6061
  		receptor	Activator, Receptor, DNA-binding,
  			Nuclear protein, Repeat,
  			Polymorphism
  NM_001628	AKR1B1	aldo-keto reductase	Oxidoreductase, NADP, Acetylation,	2094	6062
  		family 1, member B1	3D-structure, Polymorphism
  		(aldose reductase)
  NM_001629	ALOX5AP	arachidonate 5-	Transmembrane, Leukotriene	2095	6063
  		lipoxygenase-	biosynthesis
  		activating protein
  NM_001632	ALPP	alkaline	Hydrolase, Zinc, Magnesium,	2096	6064
  		phosphatase,	Phosphorylation, Transmembrane,
  		placental (Regan	Placenta, Multigene family,
  		isozyme)	Glycoprotein, GPI-anchor, Signal,
  			3D-structure, Lipoprotein
  NM_001634	AMD1	adenosylmethionine	Spermidine biosynthesis, Lyase,	2097	6065
  		decarboxylase 1	Decarboxylase, Pyruvate, Zymogen,
  			3D-structure
  NM_001637	AOAH	acyloxyacyl	Hydrolase, Signal, Transmembrane,	2098	6066
  		hydrolase	Glycoprotein
  		(neutrophil)
  NM_001643	APOA2	apolipoprotein A-II	Transport, Lipid transport, HDL,	2099	6067
  			Signal, Pyrrolidone carboxylic acid,
  			3D-structure
  NM_001654	ARAF1	v-raf murine	Transferase, Serine/threonine-	2100	6068
  		sarcoma 3611 viral	protein kinase, Proto-oncogene,
  		oncogene homolog 1	Metal-binding, Zinc, ATP-binding,
  			Phorbol-ester binding, Kinase
  NM_001657	AREG	amphiregulin	Glycoprotein, Cytokine, Growth	2101	6069
  		(schwannoma-	factor, EGF-like domain, Signal,
  		derived growth	Transmembrane
  		factor)
  NM_001662	ARF5	ADP-ribosylation	GTP-binding, Multigene family,	2102	6070
  		factor 5	Myristate, Protein transport, Golgi
  			stack, Lipoprotein
  NM_001665	ARHG	ras homolog gene	GTP-binding, Prenylation,	2103	6071
  		family, member G	Lipoprotein
  		(rho G)
  NM_001667	ARL2	sorting nexin 15	GTP-binding, Multigene family,	2104	6072
  			Hypothetical protein, Transport,
  			Protein transport, Alternative splicing
  NM_001670	ARVCF	armadillo repeat	Hypothetical protein, Cell adhesion,	2105	6073
  		gene deletes in	Cytoskeleton, Structural protein,
  		velocardiofacial	Repeat, Coiled coil, Alternative
  		syndrome	splicing
  NM_001671	ASGR1	asialoglycoprotein	Lectin, Glycoprotein, Receptor,	2106	6074
  		receptor 1	Endocytosis, Transmembrane,
  			Calcium, Signal-anchor,
  			Phosphorylation, 3D-structure
  NM_001677	ATP1B1	ATPase, Na+/K+	Transferase, Kinase, ATP-binding,	2107	6075
  		transporting,beta 1	Sodium/potassium transport,
  		polypeptide	Transmembrane, Glycoprotein,
  			Multigene family, Signal-anchor,
  			Alternative splicing
  NM_001678	ATP1B2	ATPase, Na+/K+	Sodium/potassium transport,	2108	6076
  		transporting,beta 2	Transmembrane, Glycoprotein,
  		polypeptide	Multigene family, Signal-anchor
  NM_001679	ATP1B3	ATPase, Na+/K+	Sodium/potassium transport,	2109	6077
  		transporting,beta 3	Transmembrane, Glycoprotein,
  		polypeptide	Multigene family, Signal-anchor
  NM_001681	ATP2A2	ATPase, Ca++	Hydrolase, Calcium transport,	2110	6078
  		transporting, cardiac	Transmembrane, Phosphorylation,
  		muscle, slow twitch 2	ATP-binding, Metal-binding,
  			Magnesium, Calcium-binding,
  			Multigene family, Alternative splicing,
  			Disease mutation, Epilepsy
  NM_001693	ATP6V1B2	ATPase, H+	Hydrolase, ATP synthesis, Hydrogen	2111	6079
  		transporting,	ion transport, Multigene family
  		lysosomal 56/58 kDa,
  		V1 subunit B,
  		isoform 2
  NM_001706	BCL6	B-cell	Nuclear protein, Transcription	2112	6080
  		CLL/lymphoma 6	regulation, Activator, DNA-binding,
  		(zinc finger protein	Zinc-finger, Metal-binding, Repeat,
  		51)	Proto-oncogene, Chromosomal
  			translocation, Polymorphism
  NM_001712	CEACAM1	carcinoembryonic	Alternative splicing, Immunoglobulin	2113	6081
  		antigen-related cell	domain, Signal, Transmembrane,
  		adhesion molecule 1	Glycoprotein, Repeat, Pyrrolidone
  		(biliary glycoprotein)	carboxylic acid, Hypothetical protein
  NM_001714	BICD1	Bicaudal D homolog	Golgi stack, Coiled coil, Alternative	2114	6082
  		1 (Drosophila)	splicing
  NM_001716	BLR1	Burkitt lymphoma	B-cell activation, G-protein coupled	2115	6083
  		receptor 1, GTP	receptor, Transmembrane,
  		binding protein	Glycoprotein, Alternative splicing,
  		(chemokine (C—X—C	Polymorphism
  		motif) receptor 5)
  NM_001721	BMX	BMX non-receptor	Transferase, Tyrosine-protein	2116	6084
  		tyrosine kinase	kinase, Phosphorylation, ATP-
  			binding, SH3 domain, SH2 domain
  NM_001725	BPI	bactericidal/permeability-	Antibiotic, Signal, Transmembrane,	2117	6085
  		increasing	Glycoprotein, 3D-structure
  		protein
  NM_001728	BSG	basigin (OK blood	Immunoglobulin domain,	2118	6086
  		group)	Transmembrane, Glycoprotein,
  			Signal, Antigen, Blood group
  			antigen, Polymorphism
  NM_001730	KLF5	Kruppel-like factor 5	Transcription regulation, DNA-	2119	6087
  		(intestinal)	binding, Nuclear protein, Repeat,
  			Zinc-finger, Metal-binding, Activator
  NM_001731	BTG1	B-cell translocation	Proto-oncogene, Chromosomal	2120	6088
  		gene 1, anti-	translocation
  		proliferative
  NM_001736	C5R1	complement	G-protein coupled receptor,	2121	6089
  		component 5	Transmembrane, Glycoprotein,
  		receptor 1 (C5a	Sulfation, Chemotaxis
  		ligand)
  NM_001745	CAMLG	calcium modulating	Transmembrane	2122	6090
  		ligand
  NM_001747	CAPG	capping protein	Nuclear protein, Actin-binding,	2123	6091
  		(actin filament),	Repeat, 3D-structure, Actin capping
  		gelsolin-like
  NM_001749	CAPNS1	calpain, small	Calcium-binding, Repeat, 3D-	2124	6092
  		subunit 1	structure
  NM_001750	CAST	calpastatin	Repeat, Thiol protease inhibitor,	2125	6093
  			Alternative splicing, Phosphorylation,
  			Signal transduction inhibitor
  NM_001767	CD2	CD2 antigen (p50),	Immunoglobulin domain, T-cell,	2126	6094
  		sheep red blood cell	Glycoprotein, Antigen,
  		receptor	Transmembrane, Cell adhesion,
  			Repeat, Signal, Polymorphism, 3D-
  			structure
  NM_001769	CD9	CD9 antigen (p24)	Glycoprotein, Antigen,	2127	6095
  			Transmembrane, Lipoprotein,
  			Phosphorylation
  NM_001771	CD22	CD22 antigen	Cell adhesion, Lectin, Antigen,	2128	6096
  			Transmembrane, Signal,
  			Glycoprotein, Immunoglobulin
  			domain, Repeat, Phosphorylation,
  			Alternative splicing, Polymorphism
  NM_001773	CD34	CD34 antigen	Cell adhesion, Antigen, Signal,	2129	6097
  			Transmembrane, Glycoprotein,
  			Phosphorylation, Alternative splicing
  NM_001774	CD37	CD37 antigen	Glycoprotein, Antigen,	2130	6098
  			Transmembrane, Hypothetical
  			protein
  NM_001776	ENTPD1	ectonucleoside	Hydrolase, Transmembrane,	2131	6099
  		triphosphate	Antigen, Glycoprotein, Calcium,
  		diphosphohydrolase 1	Magnesium, Alternative splicing,
  			Lipoprotein, Palmitate
  NM_001777	CD47	CD47 antigen (Rh-	Cell adhesion, Antigen, Signal,	2132	6100
  		related antigen,	Transmembrane, Glycoprotein,
  		integrin-associated	Alternative splicing
  		signal transducer)
  NM_001780	CD63	CD63 antigen	Glycoprotein, Antigen,	2133	6101
  		(melanoma 1	Transmembrane, Lysosome
  		antigen)
  NM_001781	CD69	CD69 antigen (p60,	Antigen, Signal-anchor,	2134	6102
  		early T-cell	Transmembrane, Lectin,
  		activation antigen)	Glycoprotein, Phosphorylation, 3D-
  			structure
  NM_001800	CDKN2D	cyclin-dependent	Cell cycle, Anti-oncogene, Repeat,	2135	6103
  		kinase inhibitor 2D	ANK repeat, 3D-structure
  		(p19, inhibits CDK4)
  NM_001803	CDW52	CDW52 antigen	Antigen, Signal, Glycoprotein, GPI-	2136	6104
  		(CAMPATH-1	anchor, Membrane, Polymorphism,
  		antigen)	Lipoprotein
  NM_001805	CEBPE	CCAAT/enhancer	Transcription regulation, Activator,	2137	6105
  		binding protein	DNA-binding, Nuclear protein,
  		(C/EBP), epsilon	Phosphorylation
  NM_001806	CEBPG	CCAAT/enhancer	Transcription regulation, Activator,	2138	6106
  		binding protein	DNA-binding, Nuclear protein
  		(C/EBP), gamma
  NM_001808	CELL	carboxyl ester lipase		2139	6107
  		pseudogene
  NM_001815	CEACAM3	carcinoembryonic	Immunoglobulin domain, Antigen,	2140	6108
  		antigen-related cell	Signal, Glycoprotein,
  		adhesion molecule 3	Transmembrane, Alternative
  			splicing, Polymorphism
  NM_001816	CEACAM8	carcinoembryonic	Immunoglobulin domain, Antigen,	2141	6109
  		antigen-related cell	Signal, Glycoprotein, GPI-anchor,
  		adhesion molecule 8	Repeat, Polymorphism, Lipoprotein
  NM_001817	CEACAM4	carcinoembryonic	Antigen	2142	6110
  		antigen-relatedcell
  		adhesion molecule
  4
  NM_001828	CLC	Charot-Leyden	Hydrolase, Serine esterase, Lipid	2143	6111
  		crystal protein	degradation, Galectin, Acetylation,
  			3D-structure, Polymorphism
  NM_001835	CLTCL1	clathrin, heavy	Coated pits, Alternative splicing	2144	6112
  		polypeptide-like 1
  NM_001838	CCR7	chemokine (C-C	G-protein coupled receptor,	2145	6113
  		motif) receptor 7	Transmembrane, Glycoprotein,
  			Signal
  NM_001839	CNN3	calponin	3, acidic	Calmodulin-binding, Actin-binding,	2146	6114
  			Multigene family, Repeat
  NM_001853	COL9A3	collagen, type IX,	Hypothetical protein, Collagen,	2147	6115
  		alpha 3	Extracellular matrix, Connective
  			tissue, Repeat, Hydroxylation,
  			Glycoprotein, Signal, Polymorphism
  NM_001882	CRHBP	corticotropin	Glycoprotein, Signal	2148	6116
  		releasing hormone
  		binding protein
  NM_001889	CRYZ	crystallin, zeta	Oxidoreductase, NADP, Zinc	2149	6117
  		(quinone reductase)
  NM_001894	CSNK1E	casein kinase 1,	Transferase, Serine/threonine-	2150	6118
  		epsilon	protein kinase, ATP-binding,
  			Phosphorylation, Multigene family
  NM_001907	CTRL	chymotrypsin-like	Hydrolase, Protease, Serine	2151	6119
  			protease, Transferase,
  			Serine/threonine-protein kinase,
  			ATP-binding, Phosphorylation, Golgi
  			stack, Nuclear protein, Glycoprotein,
  			Zymogen, Signal
  NM_001909	CTSD	cathepsin D	Hydrolase, Aspartyl protease,	2152	6120
  		(lysosomal aspartyl	Glycoprotein, Lysosome, Signal,
  		protease)	Zymogen, Polymorphism,
  			Alzheimer's disease, 3D-structure
  NM_001911	CTSG	cathepsin G	Hydrolase, Serine protease,	2153	6121
  			Zymogen, Glycoprotein, Signal,
  			Polymorphism, 3D-structure
  NM_001921	DCTD	dCMP deaminase	Hydrolase, Allosteric enzyme,	2154	6122
  			Nucleotide biosynthesis, Zinc
  NM_001925	DEFA4	defensin,alpha 4,	Defensin, Antibiotic, Fungicide,	2155	6123
  		corticostatin	Signal
  NM_001939	DRP2	dystrophin related	Structural protein, Cytoskeleton,	2156	6124
  		protein 2	Repeat, Zinc-finger
  NM_001940	DRPLA	dentatorubral-	Triplet repeat expansion,	2157	6125
  		pallidoluysian	Polymorphism, Epilepsy
  		atrophy (atrophin-1)
  NM_001946	DUSP6	dual specificity	Hydrolase, Polymorphism,	2158	6126
  		phosphatase 6	Alternative splicing, 3D-structure
  NM_001951	E2F5	E2F transcription	Transcription regulation, Activator,	2159	6127
  		factor 5, p130-	DNA-binding, Nuclear protein,
  		binding	Polymorphism
  NM_001953	ECGF1	endothelial cell	Transferase, Glycosyltransferase,	2160	6128
  		growth factor 1	Growth factor, Chemotaxis,
  		(platelet-derived)	Angiogenesis, Repeat,
  			Polymorphism, Disease mutation
  NM_001964	EGR1	early growth	Transcription regulation, Activator,	2161	6129
  		response 1	DNA-binding, Nuclear protein,
  			Repeat, Zinc-finger, Metal-binding
  NM_001965	EGR4	early growth	Nuclear protein, Transcription	2162	6130
  		response 4	regulation, DNA-binding, Zinc-finger,
  			Metal-binding, Repeat
  NM_001970	EIF5A	eukaryotic	Protein biosynthesis, Initiation factor,	2163	6131
  		translation initiation	Hypusine, 3D-structure
  		factor 5A
  NM_001972	ELA2	elastase	2,	Hydrolase, Serine protease,	2164	6132
  		neutrophil	Glycoprotein, Signal, 3D-structure,
  			Disease mutation
  NM_001992	F2R	coagulation factor II	G-protein coupled receptor,	2165	6133
  		(thrombin) receptor	Transmembrane, Glycoprotein,
  			Signal, Blood coagulation,
  			Phosphorylation, Polymorphism, 3D-
  			structure, Receptor
  NM_001995	FACL1	fatty-acid-Coenzyme	Ligase, Fatty acid metabolism,	2166	6134
  		A ligase, long-chain 2	Magnesium, Multigene family,
  			Hypothetical protein
  NM_001996	FBLN1	fibulin 1	Signal, Alternative splicing,	2167	6135
  			Glycoprotein, Extracellular matrix,
  			Repeat, EGF-like domain, Calcium-
  			binding, Chromosomal translocation,
  			Polymorphism, Hypothetical protein
  NM_001999	FBN2	fibrillin 2 (congenital	Hypothetical protein, EGF-like	2168	6136
  		contractural	domain, Extracellular matrix,
  		arachnodactyly)	Calcium-binding, Glycoprotein,
  			Repeat, Signal, Multigene family,
  			Disease mutation, Polymorphism
  NM_002000	FCAR	Fc fragment of IgA,	Receptor, Glycoprotein,	2169	6137
  		receptor for	Transmembrane, IgA-binding
  			protein, Immunoglobulin domain,
  			Repeat, Signal, Alternative splicing
  NM_002003	FCN1	ficolin	Lectin, Collagen, Repeat,	2170	6138
  		(collagen/fibrinogen	Glycoprotein, Signal, Multigene
  		domain containing) 1	family
  NM_002005	FES	feline sarcoma	Transferase, Tyrosine-protein	2171	6139
  		oncogene	kinase, Proto-oncogene, ATP-
  			binding, Phosphorylation, SH2
  			domain
  NM_002010	FGF9	fibroblast growth	Growth factor, Differentiation,	2172	6140
  		factor 9 (glia-	Mitogen, Heparin-binding,
  		activating factor)	Glycoprotein, 3D-structure
  NM_002013	FKBP3	FK506 binding	Isomerase, Rotamase, Nuclear	2173	6141
  		protein 3, 25 kDa	protein, 3D-structure
  NM_002014	FKBP4	FK506 binding	Isomerase, Rotamase, Repeat, TPR	2174	6142
  		protein 4, 59 kDa	repeat, Nuclear protein,
  			Phosphorylation, 3D-structure
  NM_002017	FLI1	Friend leukemia	Transcription regulation, Activator,	2175	6143
  		virus integration 1	DNA-binding, Nuclear protein,
  			Alternative splicing, Proto-oncogene,
  			Chromosomal translocation, 3D-
  			structure
  NM_002018	FLII	flightless I homolog	Developmental protein, Repeat,	2176	6144
  		(Drosophila)	Leucine-rich repeat
  NM_002029	FPR1	formyl peptide	G-protein coupled receptor,	2177	6145
  		receptor 1	Transmembrane, Glycoprotein,
  			Chemotaxis, Polymorphism
  NM_002032	FTH1	ferritin, heavy	Transport, Ion transport, Ionic	2178	6146
  		polypeptide 1	channel, Chloride channel, Chloride,
  			Calcium, Alternative splicing,
  			Disease mutation, Polymorphism,
  			Vision, Transmembrane,
  			Phosphorylation, Iron storage, Metal-
  			binding, 3D-structure
  NM_002033	FUT4	fucosyltransferase	4	Transferase, Glycosyltransferase,	2179	6147
  		(alpha (1,3)	Transmembrane, Glycoprotein,
  		fucosyltransferase,	Signal-anchor, Golgi stack
  		myeloid-specific)
  NM_002035	FVT1	follicular lymphoma	Proto-oncogene, Chromosomal	2180	6148
  		variant translocation 1	translocation, Oxidoreductase,
  			Signal
  NM_002037	FYN	FYN oncogene	Hypothetical protein, ATP-binding,	2181	6149
  		related to SRC,	SH3 domain, Transferase, Kinase,
  		FGR, YES	Tyrosine-protein kinase, Proto-
  			oncogene, Phosphorylation,
  			Myristate, SH2 domain, Palmitate,
  			Lipoprotein, 3D-structure,
  			Polymorphism
  NM_002046	GAPD	glyceraldehyde-3-	Glycolysis, NAD, Oxidoreductase,	2182	6150
  		phosphate	Multigene family
  		dehydrogenase
  NM_002051	GATA3	GATA binding	Hypothetical protein, Transcription	2183	6151
  		protein 3	regulation, Activator, DNA-binding,
  			Zinc-finger, Nuclear protein, T-cell,
  			Alternative splicing
  NM_002061	GCLM	glutamate-cysteine	Ligase, Glutathione biosynthesis	2184	6152
  		ligase, modifier
  		subunit
  NM_002064	GLRX	glutaredoxin	Redox-active center, Electron	2185	6153
  		(thioltransferase)	transport, Acetylation,
  			Polymorphism, 3D-structure
  NM_002068	GNA15	guanine nucleotide	GTP-binding, Transducer, Multigene	2186	6154
  		binding protein (G	family, ADP-ribosylation
  		protein), alpha 15
  		(Gq class)
  NM_002069	GNAI1	guanine nucleotide	Hypothetical protein, GTP-binding,	2187	6155
  		binding protein (G	Transducer, ADP-ribosylation,
  		protein), alpha	Multigene family, Myristate,
  		inhibiting activity	Palmitate, Lipoprotein, 3D-structure
  		polypeptide
  1
  NM_002070	GNAI2	guanine nucleotide	GTP-binding, Transducer, ADP-	2188	6156
  		binding protein (G	ribosylation, Multigene family,
  		protein), alpha	Myristate, Palmitate, Lipoprotein
  		inhibitingactivity
  		polypeptide
  2
  NM_002073	GNAZ	guanine nucleotide	GTP-binding, Transducer, ADP-	2189	6157
  		binding protein (G	ribosylation, Multigene family,
  		protein), alpha z	Lipoprotein, Palmitate, Myristate,
  		polypeptide	Membrane
  NM_002081	GPC1	glypican	1	Proteoglycan, Heparan sulfate,	2190	6158
  			Glycoprotein, Signal, GPI-anchor,
  			Lipoprotein
  NM_002082	GPRK6	G protein-coupled	Transferase, Serine/threonine-	2191	6159
  		receptor kinase 6	protein kinase, ATP-binding,
  			Phosphorylation, Lipoprotein,
  			Palmitate, Alternative splicing,
  			Kinase, Receptor, Hypothetical
  			protein
  NM_002086	GRB2	growth factor	SH2 domain, SH3 domain, Repeat,	2192	6160
  		receptor-bound	Alternative splicing, 3D-structure
  		protein
  2
  NM_002087	GRN	granulin	Cytokine, Repeat, Glycoprotein,	2193	6161
  			Signal, Alternative splicing,
  			Polymorphism, 3D-structure,
  			Hypothetical protein
  NM_002092	GRSF1	G-rich RNA	Hypothetical protein, RNA-binding,	2194	6162
  		sequence binding	Repeat
  		factor 1
  NM_002093	GSK3B	glycogen synthase	Transferase, Serine/threonine-	2195	6163
  		kinase 3 beta	protein kinase, ATP-binding, Wnt
  			signaling pathway, Phosphorylation,
  			Multigene family, Alternative splicing,
  			3D-structure
  NM_002096	GTF2F1	general transcription	Transcription regulation, DNA-	2196	6164
  		factor IIF,	binding, Nuclear protein,
  		polypeptide 1,	Phosphorylation, 3D-structure
  		74 kDa
  NM_002097	GTF3A	general transcription	Transcription regulation, Zinc-finger,	2197	6165
  		factor IIIA	Metal-binding, DNA-binding, RNA-
  			binding, Repeat, Nuclear protein,
  			Polymorphism, Initiation factor
  NM_002103	GYS1	glycogen synthase	1	Glycogen biosynthesis, Transferase,	2198	6166
  		(muscle)	Glycosyltransferase, Allosteric
  			enzyme, Phosphorylation, Disease
  			mutation, Diabetes mellitus,
  			Polymorphism, Hypothetical protein
  NM_002104	GZMK	granzyme K (serine	Hydrolase, Serine protease,	2199	6167
  		protease, granzyme	Zymogen, Signal, 3D-structure
  		3; tryptase II)
  NM_002105	H2AFX	H2A histone family,	Chromosomal protein, Nucleosome	2200	6168
  		member X	core, Nuclear protein, DNA-binding,
  			Multigene family, Acetylation
  NM_002107	H3F3A	H3 histone, family	Nuclear protein, Chromosomal	2201	6169
  		3A	protein, DNA-binding, Nucleosome
  			core, Multigene family
  NM_002108	HAL	histidine ammonia-	Lyase, Histidine metabolism,	2202	6170
  		lyase	Polymorphism
  NM_002109	HARS	histidyl-tRNA	Aminoacyl-tRNA synthetase, Protein	2203	6171
  		synthetase	biosynthesis, Ligase, ATP-binding,
  			Hypothetical protein, Repeat, WD
  			repeat
  NM_002110	HCK	hemopoietic cell	Transferase, Tyrosine-protein	2204	6172
  		kinase	kinase, Phosphorylation, ATP-
  			binding, Lipoprotein, Myristate,
  			Palmitate, SH2 domain, SH3
  			domain, Alternative initiation, 3D-
  			structure
  NM_002115	HK3	hexokinase 3 (white	Kinase, Transferase, Glycolysis,	2205	6173
  		cell)	Allosteric enzyme, Repeat, ATP-
  			binding, Membrane
  NM_002131	HMGA1	high mobility group	Nuclear protein, Chromosomal	2206	6174
  		AT-hook 1	protein, DNA-binding, Repeat,
  			Transcription regulation, Alternative
  			splicing, Phosphorylation,
  			Acetylation, Chromosomal
  			translocation, 3D-structure
  NM_002133	HMOX1	heme oxygenase	Cyclin, Heme, Oxidoreductase,	2207	6175
  		(decycling) 1	Microsome, Multigene family, 3D-
  			structure
  NM_002134	HMOX2	heme oxygenase	Heme, Oxidoreductase, Microsome,	2208	6176
  		(decycling) 2	Multigene family, Repeat
  NM_002136	HNRPA1	heterogeneous	Hypothetical protein, Nucleocapsid,	2209	6177
  		nuclear	Ribonucleoprotein, Nuclear protein,
  		ribonucleoprotein A1	RNA-binding, Repeat, Methylation,
  			Alternative splicing, 3D-structure,
  			Polymorphism
  NM_002139	RBMX	RNA binding motif	Hypothetical protein, Nuclear	2210	6178
  		protein, X-linked	protein, RNA-binding,
  			Ribonucleoprotein, Glycoprotein
  NM_002155	HSPA6	heat shock 70 kDa	ATP-binding, Heat shock, Multigene	2211	6179
  		protein 6 (HSP70B′)	family
  NM_002156	HSPD1	heat shock 60 kDa	Chaperone, ATP-binding,	2212	6180
  		protein 1	Mitochondrion, Transit peptide
  		(chaperonin)
  NM_002157	HSPE1	heat shock	10 kDa	Chaperone, Mitochondrion, Heat	2213	6181
  		protein 1	shock, Acetylation
  		(chaperonin 10)
  NM_002162	ICAM3	intercellular	Immunoglobulin domain, Cell	2214	6182
  		adhesion molecule 3	adhesion, Glycoprotein,
  			Transmembrane, Repeat, Signal,
  			Phosphorylation
  NM_002180	IGHMBP2	immunoglobulin mu	Hydrolase, Helicase, ATP-binding,	2215	6183
  		bindingprotein 2	DNA-binding, Nuclear protein,
  			Transcription regulation, Activator,
  			3D-structure
  NM_002191	INHA	inhibin, alpha	Growth factor, Hormone,	2216	6184
  			Glycoprotein, Signal, Polymorphism
  NM_002194	INPP1	inositol	Hydrolase, Lithium	2217	6185
  		polyphosphate-1-
  		phosphatase
  NM_002205	ITGA5	integrin,alpha 5	Integrin, Cell adhesion, Receptor,	2218	6186
  		(fibronectin receptor,	Glycoprotein, Transmembrane,
  		alpha polypeptide)	Signal, Calcium, Repeat
  NM_002209	ITGAL	integrin, alpha L	Integrin, Cell adhesion, Receptor,	2219	6187
  		(antigen CD11A	Glycoprotein, Transmembrane,
  		(p180), lymphocyte	Signal, 3D-structure, Magnesium,
  		function-associated	Calcium, Repeat,Alternative
  		antigen
  1; alpha	splicing, Hypothetical protein
  		polypeptide)
  NM_002218	ITIH4	inter-alpha (globulin)	Acute phase, Serine protease	2220	6188
  		inhibitor H4 (plasma	inhibitor, Repeat, Signal, Multigene
  		Kallikrein-sensitive	family, Glycoprotein, Alternative
  		glycoprotein)	splicing, Polymorphism
  NM_002220	ITPKA	inositol 1,4,5-	Kinase, Transferase, Calmodulin-	2221	6189
  		trisphosphate 3-	binding
  		kinase A
  NM_002222	ITPR1	inositol 1,4,5-	Receptor, Transmembrane,	2222	6190
  		triphosphate	Phosphorylation, Endoplasmic
  		receptor,type 1	reticulum, Ionic channel, Ion
  			transport, Calcium channel,
  			Alternative splicing, Repeat
  NM_002226	JAG2	jagged 2	Calcium-binding, EGF-like domain,	2223	6191
  			Glycoprotein, Developmental
  			protein, Repeat, Signal,
  			Transmembrane, Alternative splicing
  NM_002228	JUN	v-jun sarcoma virus	Proto-oncogene, Transcription	2224	6192
  		17 oncogene	regulation, DNA-binding, 3D-
  		homolog (avian)	structure, Nuclear protein,
  			Phosphorylation, Polymorphism
  NM_002236	KCNF1	potassium voltage-	Transport, Ion transport, Ionic	2225	6193
  		gated channel,	channel, Voltage-gated channel,
  		subfamily F,member 1	Potassium channel, Potassium,
  			Potassium transport,
  			Transmembrane, Multigene family
  NM_002243	KCNJ15	potassium inwardly-	Hypothetical protein, Ionic channel,	2226	6194
  		rectifying channel,	Ion transport, Voltage-gated
  		subfamily J, member	channel, Transmembrane,
  		15	Potassium transport
  NM_002250	KCNN4	potassium	Ionic channel, Transmembrane, Ion	2227	6195
  		intermediate/small	transport, Calmodulin-binding
  		conductance
  		calcium-activated
  		channel, subfamily
  		N,member 4
  NM_002258	KLRB1	killer cell lectin-like		2228	6196
  		receptor subfamily
  		B,member 1
  NM_002267	KPNA3	karyopherin alpha	3	Hypothetical protein, Transport,	2229	6197
  		(importin alpha 4)	Protein transport, Repeat, Nuclear
  			protein, Polymorphism
  NM_002271	KPNB3	karyopherin	Hypothetical protein, Transport,	2230	6198
  		(importin)beta 3	Protein transport, Repeat, Nuclear
  			protein, Polymorphism
  NM_002273	KRT8	keratin	8	Intermediate filament, Coiled coil,	2231	6199
  			Keratin, Phosphorylation
  NM_002275	KRT15	keratin	15	Intermediate filament, Coiled coil,	2232	6200
  			Keratin
  NM_002277	KRTHA1	keratin, hair, acidic, 1	Intermediate filament, Coiled coil,	2233	6201
  			Keratin
  NM_002278	KRTHA2	keratin, hair, acidic, 2	Intermediate filament, Coiled coil,	2234	6202
  			Keratin
  NM_002282	KRTHB3	keratin, hair, basic, 3	Coiled coil, Intermediate filament	2235	6203
  NM_002296	LBR	lamin B receptor	Receptor, Transmembrane,	2236	6204
  			Phosphorylation, Nuclear protein,
  			DNA-binding
  NM_002298	LCP1	lymphocyte cytosolic	Calcium-binding, Phosphorylation,	2237	6205
  		protein 1 (L-plastin)	Actin-binding, Repeat,
  			Polymorphism
  NM_002299	LCT	lactase	Hydrolase, Glycosidase, Zymogen,	2238	6206
  			Signal, Transmembrane, Repeat
  NM_002300	LDHB	lactate	Oxidoreductase, NAD, Glycolysis,	2239	6207
  		dehydrogenase B	Multigene family, Disease mutation,
  			3D-structure
  NM_002306	LGALS3	lectin, galactoside-	Galectin, Lectin, IgE-binding protein,	2240	6208
  		binding, soluble, 3	Repeat, Phosphorylation,
  		(galectin 3)	Acetylation, Nuclear protein,
  			Polymorphism, 3D-structure
  NM_002311	LIG3	ligase III, DNA, ATP-	DNA repair, DNA replication, DNA	2241	6209
  		dependent	recombination, Cell division, Ligase,
  			ATP-binding, Zinc-finger, Nuclear
  			protein, Alternative splicing, 3D-
  			structure, Hypothetical protein
  NM_002313	ABLIM1	actin binding LIM	LIM domain, Metal-binding, Zinc,	2242	6210
  		protein 1	Hypothetical protein
  NM_002316	LMX1B	LIM homeobox	DNA-binding, Homeobox, LIM	2243	6211
  		transcription factor 1,	domain, Metal-binding, Nuclear
  		beta	protein, Zinc, Developmental protein,
  			Repeat, Activator, Transcription
  			regulation, Alternative splicing,
  			Disease mutation
  NM_002332	LRP1	low density	Receptor, Transmembrane, Repeat,	2244	6212
  		lipoprotein-related	Endocytosis, Glycoprotein, Signal,
  		protein 1 (alpha-2-	Calcium-binding, EGF-like domain,
  		macroglobulin	Coated pits, 3D-structure,
  		receptor)	Polymorphism
  NM_002335	LRP5	low density	Receptor, Lipoprotein	2245	6213
  		lipoprotein receptor-
  		related protein 5
  NM_002337	LRPAP1	low density	Signal, Heparin-binding,	2246	6214
  		lipoprotein receptor-	Glycoprotein, Antigen, 3D-structure,
  		related protein	Polymorphism
  		associatedprotein 1
  NM_002339	LSP1	lymphocyte-specific	T-cell, Phosphorylation,	2247	6215
  		protein 1	Polymorphism
  NM_002341	LTB	lymphotoxin beta	Cytokine, Transmembrane,	2248	6216
  		(TNF superfamily,	Glycoprotein, Signal-anchor,
  		member 3)	Alternative splicing, Polymorphism
  NM_002343	LTF	lactotransferrin	Glycoprotein, Iron transport, Metal-	2249	6217
  			binding, Transport, Repeat, Signal,
  			Polymorphism, 3D-structure
  NM_002357	MAD	MAX dimerization	Nuclear protein, DNA-binding,	2250	6218
  		protein 1	Transcription regulation, Repressor,
  			3D-structure
  NM_002375	MAP4	microtubule-	Hypothetical protein, Microtubule,	2251	6219
  		associatedprotein 4	Repeat, Phosphorylation, Alternative
  			splicing
  NM_002382	MAX	MAX protein	Hypothetical protein, Transcription	2252	6220
  			regulation, Activator, Repressor,
  			Nuclear protein, DNA-binding,
  			Phosphorylation, Alternative splicing,
  			3D-structure
  NM_002394	SLC3A2	solute carrier family	Glycoprotein, Transmembrane,	2253	6221
  		3 (activators of	Signal-anchor
  		dibasic and neutral
  		amino acid
  		transport),member 2
  NM_002402	MEST	mesoderm specific	Aromatic hydrocarbons catabolism,	2254	6222
  		transcript homolog	Detoxification, Hydrolase,
  		(mouse)	Hypothetical protein
  NM_002406	MGAT1	mannosyl (alpha-	Transferase, Glycosyltransferase,	2255	6223
  		1,3-)-glycoprotein	Transmembrane, Signal-anchor,
  		beta-1,2-N-	Golgi stack, Hypothetical protein
  		acetylglucosaminyltransferase
  NM_002419	MAP3K11	mitogen-activated	ATP-binding, Kinase, SH3 domain,	2256	6224
  		protein kinase	Serine/threonine-protein kinase,
  		kinase kinase 11	Transferase
  NM_002424	MMP8	matrix	Hydrolase, Metalloprotease,	2257	6225
  		metalloproteinase 8	Glycoprotein, Calcium-binding,
  		(neutrophil	Metal-binding, Zinc, Zymogen,
  		collagenase)	Collagen degradation, Extracellular
  			matrix, Signal, 3D-structure
  NM_002431	MNAT1	menage a trois 1	Transcription regulation, Cell cycle,	2258	6226
  		(CAK assembly	Nuclear protein, Zinc-finger, 3D-
  		factor)	structure
  NM_002432	MNDA	myeloid cell nuclear	Interferon induction, Nuclear protein,	2259	6227
  		differentiation	DNA-binding, Transcription
  		antigen	regulation, Activator, Repressor,
  			Polymorphism
  NM_002435	MPI	mannose phosphate	Isomerase, Zinc, Disease mutation	2260	6228
  		isomerase
  NM_002442	MSI1	musashi homolog 1	RNA-binding	2261	6229
  		(Drosophila)
  NM_002453	MTIF2	mitochondrial	Initiation factor, Protein biosynthesis,	2262	6230
  		translational initiation	GTP-binding, Transit peptide,
  		factor 2	Mitochondrion, Polymorphism
  NM_002455	MTX1	metaxin 1	Mitochondrion, Outer membrane,	2263	6231
  			Transmembrane, Transport, Protein
  			transport
  NM_002475	MLC1SA	myosin light chain 1	Myosin, Muscle protein, Multigene	2264	6232
  		slow a	family
  NM_002483	CEACAM6	carcinoembryonic	Immunoglobulin domain, Signal,	2265	6233
  		antigen-related cell	Antigen, Glycoprotein, GPI-anchor,
  		adhesion molecule 6	Repeat, Lipoprotein
  		(non-specific cross
  		reacting antigen)
  NM_002486	NCBP1	nuclear cap binding	Transport, mRNA transport, Nuclear	2266	6234
  		protein subunit 1,	protein, RNA-binding, 3D-structure
  		80 kDa
  NM_002492	NDUFB5	NADH	Oxidoreductase, NAD, Ubiquinone,	2267	6235
  		dehydrogenase	Mitochondrion, Transit peptide
  		(ubiquinone) 1 beta
  		subcomplex, 5,
  		16 kDa
  NM_002495	NDUFS4	NADH	Oxidoreductase, NAD, Ubiquinone,	2268	6236
  		dehydrogenase	Mitochondrion, Transit peptide,
  		(ubiquinone) Fe—S	Polymorphism
  		protein 4, 18 kDa
  		(NADH-coenzyme Q
  		reductase)
  NM_002499	NEO1	neogenin homolog 1	Cell adhesion, Repeat, Signal,	2269	6237
  		(chicken)	Transmembrane, Immunoglobulin
  			domain, Glycoprotein, Alternative
  			splicing
  NM_002512	NME2	non-metastatic cells	Transferase, Kinase, ATP-binding,	2270	6238
  		2, protein (NM23B)	Nuclear protein, Anti-oncogene,
  		expressed in	DNA-binding, Transcription
  			regulation, Activator, 3D-structure
  NM_002517	NPAS1	neuronal PAS	Repeat, DNA-binding, Nuclear	2271	6239
  		domain protein 1	protein, Transcription regulation
  NM_002520	NPM1	nucleophosmin	Hypothetical protein, Transcription	2272	6240
  		(nucleolar	regulation, Nuclear protein, DNA-
  		phosphoprotein B23,	binding, Zinc-finger, Proto-
  		numatrin)	oncogene, Chromosomal
  			translocation, Alternative splicing,
  			Repeat, Coiled coil, 3D-structure,
  			Metal-binding, Receptor, Multigene
  			family, Phosphorylation, RNA-
  NM_002524	NRAS	neuroblastoma RAS	Hypothetical protein, RNA-binding,	2273	6241
  		viral (v-ras)	Repeat, Alternative splicing, Proto-
  		oncogene homolog	oncogene, GTP-binding, Prenylation,
  			Lipoprotein, Disease mutation
  NM_002528	NTHL1	nth endonuclease III-	Hydrolase, Nuclease, Endonuclease,	2274	6242
  		like 1 (E. coli)	Multifunctional enzyme, DNA repair,
  			Glycosidase, Lyase, Iron-sulfur, 4Fe—4S,
  			Nuclear protein, Polymorphism
  NM_002532	NUP88	nucleoporin 88 kDa	Nuclear protein, Transport, Coiled	2275	6243
  			coil
  NM_002541	OGDH	oxoglutarate (alpha-	Glycolysis, Oxidoreductase,	2276	6244
  		ketoglutarate)	Flavoprotein, Thiamine
  		dehydrogenase	pyrophosphate, Mitochondrion,
  		(lipoamide)	Transit peptide, Hypothetical protein
  NM_002543	OLR1	oxidised low density	Lectin, Lipoprotein, Receptor	2277	6245
  		lipoprotein (lectin-
  		like)receptor 1
  NM_002553	ORC5L	origin recognition	DNA replication, Nuclear protein,	2278	6246
  		complex, subunit 5-	ATP-binding, Polymorphism
  		like (yeast)
  NM_002555	SLC22A1L	solute carrier family	Hypothetical protein	2279	6247
  		22 (organic cation
  		transporter),
  		member 1-like
  NM_002557	OVGP1	oviductal	Glycoprotein, Fertilization, Signal,	2280	6248
  		glycoprotein 1,	Polymorphism
  		120 kDa (mucin 9,
  		oviductin)
  NM_002564	P2RY2	purinergic receptor	G-protein coupled receptor,	2281	6249
  		P2Y, G-protein	Transmembrane, Glycoprotein
  		coupled, 2
  NM_002573	PAFAH1B3	platelet-activating	Hydrolase, Lipid degradation	2282	6250
  		factor
  		acetylhydrolase,
  		isoform Ib, gamma
  		subunit 29 kDa
  NM_002574	PRDX1	peroxiredoxin	1	Antioxidant, Peroxidase,	2283	6251
  			Oxidoreductase, Redox-active
  			center
  NM_002576	PAK1	p21/Cdc42/Rac1-	Apoptosis, Transferase,	2284	6252
  		activatedkinase 1	Serine/threonine-protein kinase,
  		(STE20 homolog,	ATP-binding, Phosphorylation, 3D-
  		yeast)	structure, Kinase
  NM_002585	PBX1	pre-B-cell leukemia	Transcription regulation, DNA-	2285	6253
  		transcription factor 1	binding, Nuclear protein, Activator,
  			Repressor, Homeobox, Proto-
  			oncogene, Chromosomal
  			translocation, Alternative splicing,
  			Steroidogenesis, Sexual
  			differentiation, 3D-structure,
  			Phosphorylation
  NM_002587	PCDH1	protocadherin 1	Cell adhesion, Transmembrane,	2286	6254
  		(cadherin-like 1)	Calcium-binding, Repeat, Signal,
  			Alternative splicing
  NM_002598	PDCD2	programmed cell	Zinc-finger, DNA-binding, Nuclear	2287	6255
  		death 2	protein, Apoptosis
  NM_002601	PDE6D	phosphodiesterase	Hydrolase, cGMP, Vision, 3D-	2288	6256
  		6D, cGMP-specific,	structure
  		rod, delta
  NM_002608	PDGFB	platelet-derived	Mitogen, Growth factor, Proto-	2289	6257
  		growth factor beta	oncogene, Platelet, Signal,
  		polypeptide (simian	Pharmaceutical, 3D-structure,
  		sarcoma viral (v-sis)	Polymorphism, Chromosomal
  		oncogene homolog)	translocation
  NM_002611	PDK2	pyruvate	Kinase, Transferase, Transit peptide,	2290	6258
  		dehydrogenase	Mitochondrion, Multigene family
  		kinase,isoenzyme 2
  NM_002613	PDPK1	3-phosphoinositide	Transferase, Serine/threonine-	2291	6259
  		dependent protein	protein kinase, ATP-binding,
  		kinase-1	Phosphorylation, Membrane,
  			Alternative splicing, Kinase
  NM_002616	PER1	period homolog 1	Transcription regulation, Nuclear	2292	6260
  		(Drosophila)	protein, Repeat, Biological rhythms,
  			Alternative splicing
  NM_002621	PFC	properdin P factor,	Signal, Complement alternate	2293	6261
  		complement	pathway, Glycoprotein, Repeat,
  			Disease mutation
  NM_002629	PGAM1	phosphoglycerate	Isomerase, Hydrolase, Glycolysis,	2294	6262
  		mutase 1 (brain)	Acetylation, 3D-structure
  NM_002631	PGD	phosphogluconate	Oxidoreductase, Pentose shunt,	2295	6263
  		dehydrogenase	NADP
  NM_002633	PGM1	phosphoglucomutase	1	Isomerase, Phosphorylation,	2296	6264
  			Magnesium, Polymorphism,
  			Alternative splicing, Hypothetical
  			protein
  NM_002635	SLC25A3	solute carrier family	Mitochondrion, Inner membrane,	2297	6265
  		25 (mitochondrial	Repeat, Transit peptide,
  		carrier; phosphate	Transmembrane, Transport,
  		carrier),member 3	Symport, Alternative splicing,
  			Hypothetical protein
  NM_002640	SERPINB8	serine (or cysteine)	Protease inhibitor, Serine protease	2298	6266
  		proteinase inhibitor,	inhibitor, Serpin
  		clade B (ovalbumin),
  		member 8
  NM_002649	PIK3CG	phosphoinositide-3-	Kinase, Transferase, Multigene	2299	6267
  		kinase, catalytic,	family, 3D-structure
  		gamma polypeptide
  NM_002650	PIK4CA	phosphatidylinositol	Transferase, Kinase, Alternative	2300	6268
  		4-kinase, catalytic,	splicing
  		alpha polypeptide
  NM_002651	PIK4CB	phosphatidylinositol	Transferase, Kinase, Golgi stack,	2301	6269
  		4-kinase, catalytic,	Phosphorylation, Alternative splicing
  		beta polypeptide
  NM_002653	PITX1	paired-like	Homeobox, DNA-binding,	2302	6270
  		homeodomain	Developmental protein,Nuclear
  		transcription factor
  1	protein, Transcription regulation,
  			Activator
  NM_002654	PKM2	pyruvate kinase,	Transferase, Kinase, Glycolysis,	2303	6271
  		muscle	Multigene family, Magnesium,
  			Alternative splicing, Hypothetical
  			protein
  NM_002655	PLAG1	pleiomorphic	Metal-binding, Zinc, Zinc-finger	2304	6272
  		adenoma gene 1
  NM_002659	PLAUR	plasminogen	Receptor, Signal, Glycoprotein, GPI-	2305	6273
  		activator, urokinase	anchor, Repeat, Alternative splicing,
  		receptor	Polymorphism, Lipoprotein, Kinase
  NM_002661	PLCG2	phospholipase C,	Hydrolase, Lipid degradation,	2306	6274
  		gamma 2	Transducer, SH2 domain, SH3
  		(phosphatidylinositol	domain, Repeat, Calcium-binding,
  		specific)	Phosphorylation
  NM_002668	PLP2	proteolipid protein 2	Transmembrane, Glycoprotein,	2307	6275
  		(colonic epithelium-	Polymorphism
  		enriched)
  NM_002676	PMM1	phosphomannomutase	1	Isomerase	2308	6276
  NM_002685	PMSCL2	polymyositis/scleroderma	Hydrolase, Nuclease, Exonuclease,	2309	6277
  		autoantigen 2,	rRNA processing, Nuclear protein,
  		100 kDa	RNA-binding, Antigen, Alternative
  			splicing, Hypothetical protein
  NM_002686	PNMT	phenylethanolamine	Transferase, Methyltransferase,	2310	6278
  		N-methyltransferase	Catecholamine biosynthesis, 3D-
  			structure
  NM_002688	PNUTL1	peanut-like 1	Hypothetical protein, Cell division,	2311	6279
  		(Drosophila)	GTP-binding, Coiled coil, Platelet,
  			Transmembrane, Glycoprotein,
  			Hemostasis, Blood coagulation,
  			Signal, Phosphorylation, Cell
  			adhesion, Leucine-rich repeat
  NM_002691	POLD1	polymerase (DNA	DNA replication, DNA-binding, DNA-	2312	6280
  		directed),delta 1,	directed DNA polymerase,
  		catalytic subunit	Transferase, Hydrolase,
  		125 kDa	Exonuclease, Zinc-finger, Nuclear
  			protein, Polymorphism
  NM_002692	POLE2	polymerase (DNA	Transferase, DNA-directed DNA	2313	6281
  		directed),epsilon 2	polymerase, DNA replication, DNA-
  		(p59 subunit)	binding, Nuclear protein
  NM_002710	PPP1CC	protein phosphatase	Hydrolase, Metal-binding, Iron,	2314	6282
  		1, catalytic subunit,	Manganese, Glycogen metabolism,
  		gamma isoform	Multigene family, Cell division,
  			Alternative splicing, 3D-structure
  NM_002720	PPP4C	protein phosphatase	Hydrolase, Metal-binding, Iron,	2315	6283
  		4 (formerly X),	Manganese
  		catalytic subunit
  NM_002727	PRG1	proteoglycan	1,	Glycoprotein, Proteoglycan, Repeat,	2316	6284
  		secretory granule	Signal
  NM_002728	PRG2	proteoglycan	2, bone	Eosinophil, Signal, Immune	2317	6285
  		marrow (natural killer	response, Antibiotic, Lectin,
  		cell activator,	Proteoglycan, Glycoprotein, Heparin-
  		eosinophil granule	binding, 3D-structure
  		major basic protein)
  NM_002731	PRKACB	protein kinase,	ATP-binding, Kinase,	2318	6286
  		cAMP-dependent,	Serine/threonine-protein kinase,
  		catalytic, beta	Transferase, Nuclear protein, cAMP,
  			Myristate, Phosphorylation,
  			Multigene family, Lipoprotein
  NM_002733	PRKAG1	protein kinase, AMP-	Fatty acid biosynthesis, Repeat,	2319	6287
  		activated,gamma 1	CBS domain, Hypothetical protein
  		non-catalytic subunit
  NM_002738	PRKCB1	protein kinase C,	Transferase, Serine/threonine-	2320	6288
  		beta 1	protein kinase, Membrane, ATP-
  			binding, Calcium-binding, Metal-
  			binding, Zinc, Repeat, Phorbol-ester
  			binding, Phosphorylation, Alternative
  			splicing
  NM_002741	PRKCL1	protein kinase C-like 1	Transferase, ATP-binding,	2321	6289
  			Serine/threonine-protein kinase,
  			Phosphorylation, Polymorphism, 3D-
  			structure
  NM_002745	MAPK1	mitogen-activated	Transferase, Serine/threonine-	2322	6290
  		protein kinase 1	protein kinase, ATP-binding, Cell
  			cycle, Phosphorylation, 3D-structure
  NM_002748	MAPK6	mitogen-activated	Kinase, Transferase,	2323	6291
  		protein kinase 6	Serine/threonine-protein kinase,
  			ATP-binding, Cell cycle
  NM_002749	MAPK7	mitogen-activated	ATP-binding, Kinase,	2324	6292
  		protein kinase 7	Serine/threonine-protein kinase,
  			Transferase, Cell cycle,
  			Phosphorylation, Cell adhesion,
  			Extracellular matrix, Glycoprotein,
  			Calcium, Signal
  NM_002756	MAP2K3	mitogen-activated	Transferase, Serine/threonine-	2325	6293
  		protein kinase	protein kinase, Tyrosine-protein
  		kinase
  3	kinase, ATP-binding,
  			Phosphorylation, Alternative splicing,
  			Disease mutation
  NM_002757	MAP2K5	mitogen-activated	ATP-binding, Kinase,	2326	6294
  		protein kinase	Serine/threonine-protein kinase,
  		kinase 5	Transferase
  NM_002758	MAP2K6	mitogen-activated	Transferase, Serine/threonine-	2327	6295
  		protein kinase	protein kinase, Tyrosine-protein
  		kinase
  6	kinase, ATP-binding,
  			Phosphorylation, Alternative splicing
  NM_002764	PRPS1	phosphoribosyl	Nucleotide biosynthesis,	2328	6296
  		pyrophosphate	Transferase, Kinase, Magnesium,
  		synthetase 1	Multigene family, Gout, Disease
  			mutation
  NM_002765	PRPS2	phosphoribosyl	Nucleotide biosynthesis,	2329	6297
  		pyrophosphate	Transferase, Kinase, Magnesium,
  		synthetase 2	Multigene family
  NM_002767	PRPSAP2	phosphoribosyl	Nucleotide biosynthesis	2330	6298
  		pyrophosphate
  		synthetase-
  		associatedprotein 2
  NM_002770	PRSS2	protease, serine, 2	Hydrolase, Protease, Serine	2331	6299
  		(trypsin 2)	protease, Digestion, Pancreas,
  			Zymogen, Calcium-binding, Signal,
  			Multigene family
  NM_002777	PRTN3	proteinase 3 (serine	Collagen degradation, Hydrolase,	2332	6300
  		proteinase,	Serine protease, Signal, Zymogen,
  		neutrophil, Wegener	Glycoprotein, Polymorphism, 3D-
  		granulomatosis	structure
  		autoantigen)
  NM_002782	PSG6	pregnancy specific	Immunoglobulin domain,	2333	6301
  		beta-1-glycoprotein 6	Glycoprotein, Signal, Multigene
  			family, Repeat, Polymorphism,
  			Alternative splicing, Hypothetical
  			protein, Flavoprotein, Lyase,
  			Thiamine pyrophosphate
  NM_002786	PSMA1	proteasome	Proteasome, Hydrolase, Protease,	2334	6302
  		(prosome,	Acetylation, Alternative splicing,
  		macropain) subunit,	Threonine protease
  		alpha type, 1
  NM_002788	PSMA3	proteasome	Proteasome, Hydrolase, Protease,	2335	6303
  		(prosome,	Acetylation, Alternative splicing,
  		macropain) subunit,	Phosphorylation, Threonine protease
  		alpha type, 3
  NM_002790	PSMA5	proteasome	Proteasome, Hydrolase, Protease,	2336	6304
  		(prosome,	Threonine protease
  		macropain) subunit,
  		alpha type, 5
  NM_002793	PSMB1	proteasome	Proteasome, Hydrolase, Protease,	2337	6305
  		(prosome,	Threonine protease
  		macropain) subunit,
  		beta type, 1
  NM_002794	PSMB2	proteasome	Proteasome, Hydrolase, Protease,	2338	6306
  		(prosome,	Threonine protease
  		macropain) subunit,
  		beta type, 2
  NM_002796	PSMB4	proteasome	Proteasome, Hydrolase, Protease,	2339	6307
  		(prosome,	Zymogen, Polymorphism, Threonine
  		macropain) subunit,	protease
  		beta type, 4
  NM_002805	PSMC5	proteasome	ATP-binding, Proteasome	2340	6308
  		(prosome,
  		macropain) 26S
  		subunit, ATPase, 5
  NM_002807	PSMD1	proteasome	Proteasome, Repeat	2341	6309
  		(prosome,
  		macropain) 26S
  		subunit, non-
  		ATPase, 1
  NM_002809	PSMD3	proteasome	Hypothetical protein, Proteasome	2342	6310
  		(prosome,
  		macropain) 26S
  		subunit, non-
  		ATPase, 3
  NM_002815	PSMD11	proteasome	Proteasome	2343	6311
  		(prosome,
  		macropain) 26S
  		subunit, non-
  		ATPase, 11
  NM_002818	PSME2	proteasome	Proteasome, Interferon induction	2344	6312
  		(prosome,
  		macropain) activator
  		subunit 2 (PA28
  		beta)
  NM_002821	PTK7	PTK7 protein	ATP-binding, Immunoglobulin	2345	6313
  		tyrosine kinase 7	domain, Receptor, Transferase,
  			Transmembrane, Signal,
  			Glycoprotein, Cell adhesion, Repeat,
  			Hypothetical protein, Kinase,
  			Tyrosine-protein kinase
  NM_002824	PTMS	parathymosin	Hypothetical protein, Immune	2346	6314
  			response, Acetylation
  NM_002826	QSCN6	quiescin Q6	Redox-active center	2347	6315
  NM_002831	PTPN6	protein tyrosine	Hydrolase, SH2 domain, Repeat,	2348	6316
  		phosphatase, non-	Phosphorylation, Alternative splicing,
  		receptor type 6	3D-structure
  NM_002842	PTPRH	protein tyrosine	Signal	2349	6317
  		phosphatase,
  		receptor type, H
  NM_002843	PTPRJ	protein tyrosine	Signal, Glycoprotein,	2350	6318
  		phosphatase,	Transmembrane, Repeat,
  		receptor type, J	Hydrolase, Disease mutation,
  			Receptor
  NM_002850	PTPRS	protein tyrosine	Hydrolase, Receptor, Glycoprotein,	2351	6319
  		phosphatase,	Signal, Transmembrane, Cell
  		receptor type, S	adhesion, Immunoglobulin domain,
  			Alternative splicing, Repeat
  NM_002852	PTX3	pentaxin-related	Pentaxin, Glycoprotein, Signal	2352	6320
  		gene, rapidly
  		induced by IL-1 beta
  NM_002859	PXN	hypothetical protein	Cytoskeleton, Phosphorylation, LIM	2353	6321
  		FLJ23042	domain, Repeat, Metal-binding, Zinc,
  			Alternative splicing, 3D-structure,
  			Hypothetical protein
  NM_002862	PYGB	phosphorylase,	Carbohydrate metabolism,	2354	6322
  		glycogen; brain	Glycosyltransferase, Pyridoxal
  			phosphate, Transferase, Glycogen
  			metabolism, Allosteric enzyme,
  			Phosphorylation
  NM_002863	PYGL	phosphorylase,	Transferase, Glycosyltransferase,	2355	6323
  		glycogen; liver (Hers	Carbohydrate metabolism, Glycogen
  		disease, glycogen	metabolism, Allosteric enzyme,
  		storage disease type	Pyridoxal phosphate,
  		VI)	Phosphorylation, Glycogen storage
  			disease, Disease mutation,
  			Polymorphism, 3D-structure
  NM_002865	RAB2	RAB2, member RAS	GTP-binding, Transport, Protein	2356	6324
  		oncogene family	transport, Endoplasmic reticulum,
  			Golgi stack, Lipoprotein, Prenylation
  NM_002872	RAC2	ras-related C3	GTP-binding, Prenylation,	2357	6325
  		botulinum toxin	Lipoprotein, 3D-structure
  		substrate 2 (rho
  		family, small GTP
  		binding protein
  		Rac2)
  NM_002878	RAD51L3	RAD51-like 3 (S. cerevisiae)	DNA damage, DNA repair, DNA	2358	6326
  			recombination, DNA-binding, ATP-
  			binding, Nuclear protein, Alternative
  			splicing, Hypothetical protein
  NM_002880	RAF1	v-raf-1 murine	Hypothetical protein, Metal-binding,	2359	6327
  		leukemia viral	Zinc, Zinc-finger, Transferase,
  		oncogene homolog 1	Serine/threonine-protein kinase,
  			Proto-oncogene, ATP-binding,
  			Phorbol-ester binding,
  			Phosphorylation, 3D-structure,
  			Repeat
  NM_002881	RALB	v-ral simian	GTP-binding, Prenylation,	2360	6328
  		leukemia viral	Lipoprotein
  		oncogene homolog
  		B (ras related; GTP
  		binding protein)
  NM_002883	RANGAP1	Ran GTPase	Hypothetical protein, GTPase	2361	6329
  		activatingprotein 1	activation, Repeat, Leucine-rich
  			repeat, Ubl conjugation
  NM_002887	RARS	arginyl-tRNA	Aminoacyl-tRNA synthetase, Protein	2362	6330
  		synthetase	biosynthesis, Ligase, ATP-binding,
  			Alternative initiation
  NM_002893	RBBP7	retinoblastoma	Nuclear protein, Repeat, WD repeat	2363	6331
  		binding protein 7
  NM_002896	RBM4	RNA binding motif	Zinc-finger	2364	6332
  		protein 4
  NM_002897	RBMS1	RNA binding motif,	DNA-binding, DNA replication, RNA-	2365	6333
  		single stranded	binding, Nuclear protein,
  		interactingprotein 1	Phosphorylation
  NM_002901	RCN1	reticulocalbin 1, EF-	Calcium-binding, Endoplasmic	2366	6334
  		hand calcium	reticulum, Signal, Glycoprotein,
  		binding domain	Repeat, Polymorphism
  NM_002902	RCN2	reticulocalbin 2, EF-	Calcium-binding, Endoplasmic	2367	6335
  		hand calcium	reticulum, Signal, Repeat
  		binding domain
  NM_002903	RCV1	recoverin	Calcium-binding, Repeat, Myristate,	2368	6336
  			Vision, Lipoprotein
  NM_002905	RDH5	retinol	Oxidoreductase, NAD, Membrane,	2369	6337
  		dehydrogenase 5	Vision, Disease mutation,
  		(11-cis and 9-cis)	Polymorphism
  NM_002910	RENBP	renin binding protein	Isomerase	2370	6338
  NM_002918	RFX1	regulatory factor X, 1	DNA-binding, Transcription	2371	6339
  		(influences HLA	regulation, Activator, Nuclear
  		class II expression)	protein, 3D-structure
  NM_002922	RGS1	regulator of G-	Signal transduction inhibitor, B-cell	2372	6340
  		protein signalling 1	activation, Phosphorylation
  NM_002923	RGS2	regulator of G-	Signal transduction inhibitor, Cell	2373	6341
  		protein signalling 2,	cycle, Phosphorylation
  		24 kDa
  NM_002934	RNASE2	ribonuclease, RNase	Hydrolase, Nuclease, Endonuclease,	2374	6342
  		A family, 2 (liver,	Chemotaxis, Eosinophil,
  		eosinophil-derived	Glycoprotein, Signal, Polymorphism,
  		neurotoxin)	3D-structure
  NM_002935	RNASE3	ribonuclease, RNase	Hydrolase, Nuclease, Endonuclease,	2375	6343
  		A family, 3	Eosinophil, Glycoprotein, Antibiotic,
  		(eosinophil cationic	Signal, Polymorphism, 3D-structure
  		protein)
  NM_002936	RNASEH1	ribonuclease H1	Hydrolase, Nuclease, Endonuclease,	2376	6344
  			Magnesium
  NM_002939	RNH	ribonuclease/angiogenin	Repeat, Leucine-rich repeat, 3D-	2377	6345
  		inhibitor	structure, Polymorphism,
  			Hypothetical protein
  NM_002940	ABCE1	ATP-binding	Capsid assembly, Chaperone,	2378	6346
  		cassette, sub-family	Mitochondrion, ATP-binding, Repeat
  		E (OABP),member 1
  NM_002953	RPS6KA1	ribosomal protein S6	Transferase, Serine/threonine-	2379	6347
  		kinase, 90 kDa,	protein kinase, ATP-binding, Repeat,
  		polypeptide 1	Multigene family
  NM_002957	RXRA	retinoid X receptor,	Receptor, Transcription regulation,	2380	6348
  		alpha	DNA-binding, Nuclear protein, Zinc-
  			finger, Multigene family, 3D-
  			structure, Polymorphism
  NM_002961	S100A4	S100 calcium	Calcium-binding, 3D-structure	2381	6349
  		binding protein A4
  		(calcium protein,
  		calvasculin,
  		metastasin, murine
  		placental homolog)
  NM_002964	S100A8	S100 calcium	Macrophage, Calcium-binding, 3D-	2382	6350
  		binding protein A8	structure
  		(calgranulin A)
  NM_002965	S100A9	S100 calcium	Calcium-binding, Macrophage,	2383	6351
  		binding protein A9	Phosphorylation, Polymorphism, 3D-
  		(calgranulin B)	structure
  NM_002967	SAFB	scaffold attachment	Transcription regulation, Repressor,	2384	6352
  		factor B	Nuclear protein, DNA-binding, RNA-
  			binding, Phosphorylation
  NM_002969	MAPK12	mitogen-activated	Transferase, Serine/threonine-	2385	6353
  		protein kinase 12	protein kinase, ATP-binding, Cell
  			cycle, Phosphorylation,
  			Polymorphism, 3D-structure
  NM_002978	SCNN1D	sodium channel,	Ion transport, Sodium transport,	2386	6354
  		nonvoltage-gated 1,	Ionic channel, Transmembrane,
  		delta	Glycoprotein, Alternative splicing,
  			Sodium channel
  NM_002984	CCL4	chemokine (C-C	Cytokine, Chemotaxis, Inflammatory	2387	6355
  		motif)ligand 4	response, Signal, 3D-structure
  NM_002985	CCL5	chemokine (C-C	Cytokine, Chemotaxis, T-cell, Signal,	2388	6356
  		motif)ligand 5	Inflammatory response, 3D-structure
  NM_003003	SEC14L1	SEC14-like 1 (S. cerevisiae)		2389	6357
  NM_003006	SELPLG	selectin P ligand	Hypothetical protein, Cell adhesion,	2390	6358
  			Glycoprotein, Transmembrane,
  			Signal, Repeat, Polymorphism,
  			Sulfation, 3D-structure, Lectin,
  			Selectin
  NM_003011	SET	SET translocation	Proto-oncogene, Chromosomal	2391	6359
  		(myeloid leukemia-	translocation, Nuclear protein,
  		associated)	Phosphorylation
  NM_003021	SGT	small glutamine-rich	Chaperone, Repeat, TPR repeat,	2392	6360
  		tetratricopeptide	Hypothetical protein
  		repeat (TPR)-
  		containing, alpha
  NM_003040	SLC4A2	solute carrier family	Transmembrane, Glycoprotein,	2393	6361
  		4, anion exchanger,	Transport, Antiport, Ion transport,
  		member 2	Anion exchange, Lipoprotein,
  		(erythrocyte	Palmitate, Alternative splicing
  		membrane protein
  		band 3-like 1)
  NM_003044	SLC6A12	solute carrier family	Neurotransmitter transport,	2394	6362
  		6 (neurotransmitter	Transport, Transmembrane,
  		transporter,	Glycoprotein, Symport
  		betaine/GABA),
  		member 12
  NM_003055	SLC18A3	choline	Transport, Neurotransmitter	2395	6363
  		acetyltransferase	transport, Transmembrane,
  			Glycoprotein
  NM_003056	SLC19A1	solute carrier family	Folate-binding, Transport,	2396	6364
  		19 (folate	Transmembrane, Glycoprotein
  		transporter),
  		member 1
  NM_003057	SLC22A1	solute carrier family	Transmembrane	2397	6365
  		22 (organic cation
  		transporter),
  		member 1
  NM_003059	SLC22A4	solute carrier family	Transmembrane	2398	6366
  		22 (organic cation
  		transporter),
  		member 4
  NM_003064	SLPI	secretory leukocyte	Serine protease inhibitor, Repeat,	2399	6367
  		protease inhibitor	Signal
  		(antileukoproteinase)
  NM_003066	SLPI	secretory leukocyte	Serine protease inhibitor, Repeat,	2400	6368
  		protease inhibitor	Signal
  		(antileukoproteinase)
  NM_003071	SMARCA3	SWI/SNF related,	ATP-binding, DNA-binding, Helicase,	2401	6369
  		matrix associated,	Hydrolase, Metal-binding, Zinc, Zinc-
  		actin dependent	finger
  		regulator of
  		chromatin, subfamily
  		a,member 3
  NM_003073	SMARCB1	SWI/SNF related,	Hypothetical protein, Transcription	2402	6370
  		matrix associated,	regulation, Activator, Nuclear
  		actin dependent	protein, Alternative splicing, Anti-
  		regulator of	oncogene
  		chromatin, subfamily
  		b,member 1
  NM_003074	SMARCC1	SWI/SNF related,	DNA-binding, Nuclear protein	2403	6371
  		matrix associated,
  		actin dependent
  		regulator of
  		chromatin, subfamily
  		c,member 1
  NM_003077	SMARCD2	SWI/SNF related,		2404	6372
  		matrix associated,
  		actin dependent
  		regulator of
  		chromatin, subfamily
  		d,member 2
  NM_003079	SMARCE1	SWI/SNF related,		2405	6373
  		matrix associated,
  		actin dependent
  		regulator of
  		chromatin, subfamily
  		e,member 1
  NM_003084	SNAPC3	small nuclear RNA	Hypothetical protein, Transcription	2406	6374
  		activating complex,	regulation, DNA-binding
  		polypeptide
  3,
  		50 kDa
  NM_003085	SNCB	synuclein, beta	Phosphorylation, Repeat	2407	6375
  NM_003086	SNAPC4	small nuclear RNA	DNA-binding, Nuclear protein,	2408	6376
  		activating complex,	Hypothetical protein
  		polypeptide
  4,
  		190 kDa
  NM_003088	FSCN1	fascin homolog 1,	Actin-binding, Acetylation,	2409	6377
  		actin-bundling	Phosphorylation, 3D-structure,
  		protein	Hypothetical protein
  		(Strongylocentrotus
  		purpuratus)
  NM_003090	SNRPA1	small nuclear	Nuclear protein, RNA-binding,	2410	6378
  		ribonucleoprotein	Ribonucleoprotein, Leucine-rich
  		polypeptide A′	repeat, Repeat, 3D-structure
  NM_003092	SNRPB2	small nuclear	mRNA processing, mRNA splicing,	2411	6379
  		ribonucleoprotein	Nuclear protein, RNA-binding,
  		polypeptide B″	Ribonucleoprotein, Repeat,
  			Systemic lupus erythematosus, 3D-
  			structure
  NM_003093	SNRPC	small nuclear	Nuclear protein, RNA-binding,	2412	6380
  		ribonucleoprotein	Ribonucleoprotein, Zinc-finger
  		polypeptide C
  NM_003094	SNRPE	small nuclear	Nuclear protein, Ribonucleoprotein,	2413	6381
  		ribonucleoprotein	Systemic lupus erythematosus,
  		polypeptide E	mRNA splicing, mRNA processing,
  			RNA-binding
  NM_003100	SNX2	sorting nexin	2	Transport, Protein transport	2414	6382
  NM_003104	SORD	sorbitol	Oxidoreductase, Zinc, Metal-binding,	2415	6383
  		dehydrogenase	NAD, Acetylation, Polymorphism
  NM_003105	SORL1	sortilin-related	Endocytosis, Receptor,	2416	6384
  		receptor, L(DLR	Transmembrane, EGF-like domain,
  		class) A repeats-	Repeat, Glycoprotein, LDL, Lipid
  		containing	transport, Cholesterol metabolism,
  			Signal
  NM_003107	SOX4	SRY (sex	DNA-binding, Nuclear protein,	2417	6385
  		determining region	Transcription regulation, Activator
  		Y)-box 4
  NM_003120	SPI1	spleen focus forming	Proto-oncogene, DNA-binding,	2418	6386
  		virus (SFFV) proviral	Transcription regulation, Activator,
  		integration oncogene	Nuclear protein
  		spi1
  NM_003135	SRP19	signal recognition	Signal recognition particle, RNA-	2419	6387
  		particle 19 kDa	binding, Ribonucleoprotein, 3D-
  			structure
  NM_003141	SSA1	Sjogren syndrome	Systemic lupus erythematosus, Zinc-	2420	6388
  		antigen A1 (52 kDa,	finger, Antigen, RNA-binding,
  		ribonucleoprotein	Ribonucleoprotein, DNA-binding,
  		autoantigen SS-	Polymorphism
  		A/Ro)
  NM_003143	SSBP1	single-stranded DNA	DNA-binding, DNA replication,	2421	6389
  		binding protein 1	Mitochondrion, Transit peptide, 3D-
  			structure
  NM_003146	SSRP1	structure specific	DNA-binding, Nuclear protein	2422	6390
  		recognition protein 1
  NM_003150	STAT3	signal transducer	Hypothetical protein, Transcription	2423	6391
  		and activator of	regulation, Activator, DNA-binding,
  		transcription 3	Nuclear protein, Phosphorylation,
  		(acute-phase	SH2 domain
  		response factor)
  NM_003153	STAT6	signal transducer	Transcription regulation, Repressor,	2424	6392
  		and activator of	Alternative splicing, Activator, DNA-
  		transcription 6,	binding, Nuclear protein,
  		interleukin-4 induced	Phosphorylation, SH2 domain,
  			Polymorphism
  NM_003163	STX1B1	Human mRNA for	Neurotransmitter transport, Coiled	2425	6393
  		SYNTAXIN1B,	coil, Transmembrane
  		complete cds.
  NM_003168	SUPT4H1	suppressor of Ty 4	Nuclear protein, Transcription, Zinc-	2426	6394
  		homolog 1 (S. cerevisiae)	finger
  NM_003169	SUPT5H	suppressor of Ty 5		2427	6395
  		homolog (S. cerevisiae)
  NM_003171	SUPV3L1	suppressor of var1,	ATP-binding, Helicase, Hydrolase	2428	6396
  		3-like 1 (S. cerevisiae)
  NM_003174	SVIL	supervillin		2429	6397
  NM_003177	SYK	spleen tyrosine	Transferase, Tyrosine-protein	2430	6398
  		kinase	kinase, ATP-binding,
  			Phosphorylation, SH2 domain,
  			Repeat, Alternative splicing, 3D-
  			structure
  NM_003190	TAPBP	TAP binding protein	Immunoglobulin domain, Signal,	2431	6399
  		(tapasin)	Transmembrane, Endoplasmic
  			reticulum, Microsome, Alternative
  			splicing, Polymorphism
  NM_003191	TARS	hypothetical protein	Aminoacyl-tRNA synthetase, Protein	2432	6400
  		MGC9344	biosynthesis, Ligase, ATP-binding
  NM_003193	TBCE	tubulin-specific		2433	6401
  		chaperone e
  NM_003197	TCEB1L	S-phase kinase-	Ubl conjugation pathway, Alternative	2434	6402
  		associated protein	splicing, 3D-structure
  		1A (p19A)
  NM_003199	TCF4	transcription factor	4	Transcription regulation, DNA-	2435	6403
  			binding, Activator, Nuclear protein,
  			Alternative splicing
  NM_003201	TFAM	transcription factor	Transcription regulation, DNA-	2436	6404
  		A, mitochondrial	binding, Activator, Mitochondrion,
  			Transit peptide, Repeat,
  			Polymorphism
  NM_003202	TCF7	transcription factor 7	Transcription regulation, Activator,	2437	6405
  		(T-cell specific,	Repressor, Trans-acting factor,
  		HMG-box)	Nuclear protein, DNA-binding, Wnt
  			signaling pathway, Alternative
  			splicing, Alternative promoter usage
  NM_003203	C2orf3	chromosome	2 open		2438	6406
  		reading frame 3
  NM_003205	TCF12	transcription factor	Transcription regulation, DNA-	2439	6407
  		12 (HTF4, helix-	binding, Nuclear protein,
  		loop-helix	Developmental protein
  		transcription factors
  		4)
  NM_003217	TEGT	testis enhanced	Apoptosis, Transmembrane	2440	6408
  		gene transcript (BAX
  		inhibitor 1)
  NM_003226	TFF3	trefoil factor	3	Signal, 3D-structure	2441	6409
  		(intestinal)
  NM_003227	TFR2	transferrin receptor	2	Transmembrane, Glycoprotein,	2442	6410
  			Receptor, Signal-anchor, Alternative
  			splicing, Disease mutation
  NM_003236	TGFA	transforming growth	EGF-like domain, Growth factor,	2443	6411
  		factor, alpha	Mitogen, Glycoprotein,
  			Transmembrane, Signal, 3D-
  			structure, Lipoprotein, Palmitate
  NM_003245	TGM3	transglutaminase	3	Transferase, Acyltransferase,	2444	6412
  		(E polypeptide,	Calcium-binding, Zymogen,
  		protein-glutamine-	Keratinization, 3D-structure
  		gamma-
  		glutamyltransferase)
  NM_003248	THBS4	thrombospondin	4	Glycoprotein, Cell adhesion,	2445	6413
  			Calcium-binding, Repeat, EGF-like
  			domain, Signal
  NM_003252	TIAL1	TIA1 cytotoxic	RNA-binding, Apoptosis, Repeat	2446	6414
  		granule-associated
  		RNA binding protein-
  		like 1
  NM_003255	TIMP2	tissue inhibitor of	Hypothetical protein,	2447	6415
  		metalloproteinase 2	Metalloprotease inhibitor, Signal, 3D-
  			structure
  NM_003263	TLR1	toll-like receptor 1	Receptor, Immune response,	2448	6416
  			Inflammatory response, Signal,
  			Transmembrane, Repeat, Leucine-
  			rich repeat, Glycoprotein, 3D-
  			structure
  NM_003274	TMEM1	transmembrane	Transport, Endoplasmic reticulum,	2449	6417
  		protein 1	Golgi stack, Polymorphism
  NM_003281	TNNI1	troponin I, skeletal,	Muscle protein, Actin-binding, Ubl	2450	6418
  		slow	conjugation pathway, Hydrolase,
  			Thiol protease, Multigene family
  NM_003288	TPD52L2	tumor protein D52-	Coiled coil, Alternative splicing	2451	6419
  		like 2
  NM_003289	TPM2	tropomyosin 2 (beta)	Muscle protein, Cytoskeleton, Actin-	2452	6420
  			binding, Coiled coil, Alternative
  			splicing, Multigene family,
  			Acetylation, Disease mutation
  NM_003290	TPM4	tropomyosin	4	Muscle protein, Cytoskeleton, Actin-	2453	6421
  			binding, Coiled coil, Alternative
  			splicing, Multigene family
  NM_003299	TRA1	tumor rejection	Chaperone, Endoplasmic reticulum,	2454	6422
  		antigen (gp96) 1	Glycoprotein, Calcium-binding,
  			Signal
  NM_003307	TRPM2	Homo sapiens	Ionic channel, Transmembrane, Ion	2455	6423
  		transient receptor	transport, Calcium channel,
  		potential cation	Alternative splicing
  		channel, subfamily
  		M, member 2
  		(TRPM2), mRNA.
  NM_003310	TSSC1	tumor suppressing	Repeat, WD repeat	2456	6424
  		subtransferable
  		candidate 1
  NM_003316	TTC3	tetratricopeptide	Metal-binding, Zinc, Zinc-finger,	2457	6425
  		repeat domain 3	Repeat, TPR repeat, Alternative
  			splicing, Polymorphism
  NM_003326	TNFSF4	tumor necrosis factor	Cytokine, Transmembrane,	2458	6426
  		(ligand) superfamily,	Glycoprotein, Signal-anchor
  		member 4 (tax-
  		transcriptionally
  		activated
  		glycoprotein 1,
  		34 kDa)
  NM_003329	TXN	thioredoxin	Redox-active center, Electron	2459	6427
  			transport, 3D-structure
  NM_003330	TXNRD1	thioredoxin	Redox-active center,	2460	6428
  		reductase 1	Oxidoreductase, NADP,
  			Flavoprotein, FAD
  NM_003331	TYK2	tyrosine kinase 2	Transferase, Tyrosine-protein	2461	6429
  			kinase, ATP-binding,
  			Phosphorylation, SH2 domain,
  			Repeat
  NM_003332	TYROBP	TYRO protein	Transmembrane, Signal,	2462	6430
  		tyrosine kinase	Phosphorylation, Polymorphism,
  		binding protein	Receptor
  NM_003338	UBE2D1	ubiquitin-conjugating	Ubl conjugation pathway, Ligase,	2463	6431
  		enzyme E2D 1	Multigene family
  		(UBC4/5 homolog,
  		yeast)
  NM_003341	UBE2E1	ubiquitin-conjugating	Ubl conjugation pathway, Ligase,	2464	6432
  		enzyme E2E 1	Multigene family
  		(UBC4/5 homolog,
  		yeast)
  NM_003343	UBE2G2	ubiquitin-conjugating	Ubl conjugation pathway, Ligase,	2465	6433
  		enzyme E2G 2	Multigene family, Hypothetical
  		(UBC7 homolog,	protein
  		yeast)
  NM_003348	UBE2N	ubiquitin-conjugating	Ubl conjugation pathway, Ligase,	2466	6434
  		enzyme E2N	Multigene family, 3D-structure
  		(UBC13 homolog,
  		yeast)
  NM_003355	UCP2	uncoupling protein 2	Mitochondrion, Inner membrane,	2467	6435
  		(mitochondrial,	Repeat, Transmembrane, Transport,
  		proton carrier)	Polymorphism
  NM_003358	UGCG	UDP-glucose	Transferase, Glycosyltransferase,	2468	6436
  		ceramide	Transmembrane, Signal-anchor,
  		glucosyltransferase	Endoplasmic reticulum
  NM_003362	UNG	uracil-DNA	DNA repair, Hydrolase, Glycosidase,	2469	6437
  		glycosylase	Nuclear protein, Mitochondrion,
  			Transit peptide, Disease mutation,
  			Alternative splicing, 3D-structure
  NM_003364	UP	uridine	Transferase, Glycosyltransferase,	2470	6438
  		phosphorylase 1	Alternative splicing
  NM_003366	UQCRC2	ubiquinol-	Mitochondrion, Inner membrane,	2471	6439
  		cytochrome c	Electron transport, Respiratory
  		reductase core	chain, Oxidoreductase, Transit
  		protein II	peptide
  NM_003370	VASP	vasodilator-	Phosphorylation, Actin-binding, 3D-	2472	6440
  		stimulated	structure
  		phosphoprotein
  NM_003374	VDAC1	voltage-dependent	Outer membrane, Porin,	2473	6441
  		anion channel 1	Mitochondrion, Acetylation
  NM_003375	VDAC2	voltage-dependent	Outer membrane, Porin,	2474	6442
  		anion channel 2	Mitochondrion, Alternative splicing,
  			Polymorphism
  NM_003377	VEGFB	vascular endothelial	Mitogen, Growth factor,	2475	6443
  		growth factor B	Glycoprotein, Signal, Heparin-
  			binding, Alternative splicing,
  			Multigene family
  NM_003387	WASPIP	Wiskott-Aldrich	Actin-binding, Repeat,	2476	6444
  		syndrome protein	Polymorphism
  		interacting protein
  NM_003389	CORO2A	coronin, actin	Actin-binding, Repeat, WD repeat,	2477	6445
  		binding protein, 2A	Coiled coil
  NM_003403	YY1	YY1 transcription	Transcription regulation, Repressor,	2478	6446
  		factor	Activator, Nuclear protein, Zinc-
  			finger, Metal-binding, DNA-binding,
  			Repeat, 3D-structure
  NM_003407	ZFP36	zinc finger protein	Nuclear protein, Repeat, Metal-	2479	6447
  		36, C3H type,	binding, Zinc-finger, DNA-binding
  		homolog (mouse)
  NM_003426	ZNF74	zinc finger protein 74	Transcription regulation, DNA-	2480	6448
  		(Cos52)	binding, RNA-binding, Zinc-finger,
  			Metal-binding, Nuclear protein,
  			Repeat, Alternative splicing,
  			Polymorphism
  NM_003451	ZNF177	zinc finger protein	Transcription regulation, DNA-	2481	6449
  		177	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat,
  			Hypothetical protein
  NM_003457	ZNF207	zinc finger protein	Zinc-finger, Metal-binding, DNA-	2482	6450
  		207	binding, Nuclear protein, Alternative
  			splicing, Hypothetical protein
  NM_003461	ZYX	zyxin	LIM domain, Metal-binding, Zinc,	2483	6451
  			Repeat, Cell adhesion, Receptor
  NM_003465	CHIT1	chitinase 1	Carbohydrate metabolism, Chitin	2484	6452
  		(chitotriosidase)	degradation, Polysaccharide
  			degradation, Hydrolase,
  			Glycosidase, Chitin-binding, Signal,
  			Alternative splicing, 3D-structure
  NM_003466	PAX8	paired box gene 8	DNA-binding, Developmental	2485	6453
  			protein, Nuclear protein, Paired box,
  			Transcription, Transcription
  			regulation, Differentiation, Alternative
  			splicing, Disease mutation,
  			Polymorphism
  NM_003467	CXCR4	chemokine (C—X—C	G-protein coupled receptor,	2486	6454
  		motif) receptor 4	Receptor, Transmembrane,
  			Glycoprotein, Sulfation, Antigen,
  			Alternative splicing
  NM_003475	C11orf13	chromosome 11	Coiled coil, Alternative splicing	2487	6455
  		open reading frame
  		13
  NM_003477	PDX1	pyruvate	Transit peptide, Mitochondrion,	2488	6456
  		dehydrogenase	Lipoyl, Hypothetical protein,
  		complex, component X	Acyltransferase, Transferase
  NM_003489	NRIP1	nuclear receptor	Transcription regulation, Nuclear	2489	6457
  		interacting protein 1	protein
  NM_003493	HIST3H3	histone 3, H3	Nuclear protein, Chromosomal	2490	6458
  			protein, DNA-binding, Nucleosome
  			core, Multigene family, Acetylation,
  			Methylation
  NM_003494	DYSF	dysferlin, limb girdle	Transmembrane, Repeat, Disease	2491	6459
  		muscular dystrophy	mutation, Hypothetical protein
  		2B (autosomal
  		recessive)
  NM_003498	SNN	stannin	Transmembrane, Hypothetical	2492	6460
  			protein
  NM_003507	FZD7	frizzled homolog 7	Multigene family, G-protein coupled	2493	6461
  		(Drosophila)	receptor, Transmembrane,
  			Developmental protein, Wnt
  			signaling pathway, Glycoprotein,
  			Signal
  NM_003508	FZD9	frizzled homolog 9	Multigene family, G-protein coupled	2494	6462
  		(Drosophila)	receptor, Transmembrane,
  			Developmental protein, Wnt
  			signaling pathway, Glycoprotein,
  			Signal
  NM_003530	HIST1H3D	histone 1, H3d	Nuclear protein, Chromosomal	2495	6463
  			protein, DNA-binding, Nucleosome
  			core, Multigene family, Acetylation,
  			Methylation
  NM_003532	HIST1H3E	histone 1, H3c	Nuclear protein, Chromosomal	2496	6464
  			protein, DNA-binding, Nucleosome
  			core, Multigene family, Acetylation,
  			Methylation
  NM_003534	HIST1H3G	histone 1, H3g	Nuclear protein, Chromosomal	2497	6465
  			protein, DNA-binding, Nucleosome
  			core, Multigene family, Acetylation,
  			Methylation
  NM_003535	HIST1H3J	histone 1, H3j	Nuclear protein, Chromosomal	2498	6466
  			protein, DNA-binding, Nucleosome
  			core, Multigene family, Acetylation,
  			Methylation
  NM_003549	HYAL3	hyaluronoglucosaminidase 3	EGF-like domain	2499	6467
  NM_003560	PLA2G6	phospholipase A2,	Hypothetical protein, ANK repeat,	2500	6468
  		group VI (cytosolic,	Repeat, Hydrolase, Lipid
  		calcium-	degradation, Membrane, Alternative
  		independent)	splicing
  NM_003562	SLC25A11	solute carrier family	Mitochondrion, Inner membrane,	2501	6469
  		25 (mitochondrial	Repeat, Transmembrane, Transport
  		carrier; oxoglutarate
  		carrier), member 11
  NM_003565	ULK1	unc-51-like kinase 1	Hypothetical protein, ATP-binding,	2502	6470
  		(C. elegans)	Transferase, Serine/threonine-
  			protein kinase
  NM_003570	CMAH	MRNA for CMP-N-		2503	6471
  		acetylneuraminic
  		acid hydroxylase,
  		complete cds.
  NM_003577	UTF1	undifferentiated		2504	6472
  		embryoniccell
  		transcription factor
  1
  NM_003579	RAD54L	RAD54-like (S. cerevisiae)	ATP-binding, DNA repair, Helicase,	2505	6473
  			Hydrolase
  NM_003587	DDX16	DEAH (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	2506	6474
  		His) box polypeptide	mRNA processing, mRNA splicing,
  		16	Nuclear protein
  NM_003599	SUPT3H	suppressor of Ty 3	Transcription regulation, Activator,	2507	6475
  		homolog (S. cerevisiae)	Nuclear protein, Alternative splicing
  NM_003601	SMARCA5	SWI/SNF related,	ATP-binding, DNA-binding, Helicase,	2508	6476
  		matrix associated,	Hydrolase, Nuclear protein
  		actin dependent
  		regulator of
  		chromatin, subfamily
  		a,member 5
  NM_003618	MAP4K3	mitogen-activated	ATP-binding, Kinase, Transferase	2509	6477
  		protein kinase
  		kinase kinase kinase 3
  NM_003624	RANBP3	RAN bindingprotein 3	Hypothetical protein	2510	6478
  NM_003634	NIPSNAP1	nipsnaphomolog 1	Polymorphism	2511	6479
  		(C. elegans)
  NM_003635	NDST2	N-deacetylase/N-	Hypothetical protein, Transferase,	2512	6480
  		sulfotransferase	Transmembrane, Glycoprotein, Golgi
  		(heparan	stack, Signal-anchor
  		glucosaminyl) 2
  NM_003636	KCNAB2	potassium voltage-	Ionic channel, Ion transport,	2513	6481
  		gated channel,	Potassium transport, Voltage-gated
  		shaker-related	channel, Alternative splicing
  		subfamily,beta
  		member
  2
  NM_003639	IKBKG	inhibitor of kappa	Coiled coil, Transcription regulation,	2514	6482
  		light polypeptide	Nuclear protein, Disease mutation,
  		gene enhancer in B-	Anhidrotic ectodermal dysplasia,
  		cells, kinase gamma	Repeat, LIM domain, Metal-binding,
  			Zinc, Developmental protein,
  			Differentiation, Zinc-finger
  NM_003644	GAS7	growth arrest-	Neurogenesis, Developmental	2515	6483
  		specific 7	protein, Coiled coil, Proto-oncogene,
  			Chromosomal translocation,
  			Alternative splicing
  NM_003648	DGKD	diacylglycerol	Transferase, Kinase, Phorbol-ester	2516	6484
  		kinase, delta 130 kDa	binding, Repeat, Multigene family
  NM_003650	CST7	cystatin F	Thiol protease inhibitor,	2517	6485
  		(leukocystatin)	Glycoprotein, Signal
  NM_003655	CBX4	chromobox homolog	Chromatin regulator, Nuclear	2518	6486
  		4 (Pc class homolog,	protein, Transcription regulation,
  		Drosophila)	Repressor, Alternative splicing
  NM_003668	MAPKAPK5	mitogen-activated	Hypothetical protein, ATP-binding,	2519	6487
  		protein kinase-	Kinase, Serine/threonine-protein
  		activated protein	kinase, Transferase
  		kinase 5
  NM_003674	CDK10	cyclin-dependent	Transferase, Serine/threonine-	2520	6488
  		kinase (CDC2-like)	protein kinase, ATP-binding, Kinase,
  		10	Cyclin
  NM_003680	YARS	tyrosyl-tRNA	Aminoacyl-tRNA synthetase, Protein	2521	6489
  		synthetase	biosynthesis, Ligase, ATP-binding,
  			RNA-binding, tRNA-binding, 3D-
  			structure
  NM_003681	PDXK	pyridoxal	Transferase, Kinase, Alternative	2522	6490
  		(pyridoxine, vitamin	splicing
  		B6) kinase
  NM_003682	MADD	MAP-kinase	Hypothetical protein, Kinase	2523	6491
  		activating death
  		domain
  NM_003685	KHSRP	KH-type splicing	Transport, mRNA transport, mRNA	2524	6492
  		regulatory protein	processing, mRNA splicing,
  		(FUSE binding	Transcription regulation, Trans-
  		protein 2)	acting factor, Nuclear protein, DNA-
  			binding, RNA-binding, Repeat
  NM_003686	EXO1	exonuclease 1	Exonuclease, Hypothetical protein	2525	6493
  NM_003690	PRKRA	protein kinase,	Hypothetical protein, Kinase	2526	6494
  		interferon-inducible
  		double stranded
  		RNA dependent
  		activator
  NM_003707	RUVBL1	RuvB-like 1 (E. coli)	Transcription, DNA recombination,	2527	6495
  			ATP-binding, Hydrolase, Helicase,
  			Nuclear protein
  NM_003709	KLF7	Kruppel-like factor 7	Transcription regulation, Activator,	2528	6496
  		(ubiquitous)	Zinc-finger, Metal-binding, DNA-
  			binding, Nuclear protein, Repeat
  NM_003713	PPAP2B	phosphatidic acid	Collagen, Hydrolase, Hypothetical	2529	6497
  		phosphatase type	protein
  		2B
  NM_003725	RODH	3-hydroxysteroid	Oxidoreductase	2530	6498
  		epimerase
  NM_003726	SCAP1	src family associated	SH3 domain	2531	6499
  		phosphoprotein 1
  NM_003730	RNASE6PL	ribonuclease T2	Hydrolase, Nuclease, Endonuclease,	2532	6500
  			Glycoprotein, Signal, Alternative
  			splicing, Polymorphism, Hypothetical
  			protein
  NM_003734	AOC3	amine oxidase,	Oxidoreductase, Copper, TPQ,	2533	6501
  		copper containing 3	Glycoprotein, Transmembrane,
  		(vascular adhesion	Signal-anchor, Cell adhesion,
  		protein 1)	Polymorphism, Metal-binding
  NM_003748	ALDH4A1	aldehyde	Oxidoreductase, NAD, Proline	2534	6502
  		dehydrogenase 4	metabolism, Mitochondrion, Transit
  		family, member A1	peptide, Polymorphism, Disease
  			mutation
  NM_003750	EIF3S10	eukaryotic	Initiation factor, Protein biosynthesis,	2535	6503
  		translation initiation	Repeat,Phosphorylation
  		factor
  3,subunit 10
  		theta, 150/170 kDa
  NM_003754	EIF3S5	eukaryotic	Initiation factor, Protein biosynthesis,	2536	6504
  		translation initiation	Polymorphism,Hypothetical protein
  		factor
  3,subunit 5
  		epsilon, 47 kDa
  NM_003755	EIF3S4	eukaryotic	Initiation factor, Protein biosynthesis,	2537	6505
  		translation initiation	RNA-binding
  		factor
  3,subunit 4
  		delta, 44 kDa
  NM_003756	EIF3S3	eukaryotic	Initiation factor, Protein biosynthesis	2538	6506
  		translation initiation
  		factor
  3,subunit 3
  		gamma, 40 kDa
  NM_003758	EIF3S1	eukaryotic	Hypothetical protein, Initiation factor,	2539	6507
  		translation initiation	Protein biosynthesis
  		factor
  3,subunit 1
  		alpha, 35 kDa
  NM_003764	STX11	syntaxin 11	Coiled coil, Membrane,	2540	6508
  			Polymorphism
  NM_003765	STX10	syntaxin	10	Coiled coil, Transmembrane,	2541	6509
  			Transport, Protein transport, Golgi
  			stack, Alternative splicing
  NM_003769	SFRS9	splicing factor,	Nuclear protein, RNA-binding,	2542	6510
  		arginine/serine-rich 9	mRNA splicing, Repeat,
  			Phosphorylation
  NM_003776	MRPL40	mitochondrial	Ribosomal protein, Mitochondrion,	2543	6511
  		ribosomal protein	Transit peptide, Polymorphism
  		L40
  NM_003782	B3GALT4	UDP-	Transferase, Glycosyltransferase,	2544	6512
  		Gal:betaGlcNAc	Glycoprotein, Transmembrane,
  		beta 1,3-	Signal-anchor, Golgi stack
  		galactosyltransferase,
  		polypeptide 4
  NM_003786	ABCC3	ATP-binding	ATP-binding, Glycoprotein,	2545	6513
  		cassette, sub-family	Transmembrane, Transport, Repeat,
  		C (CFTR/MRP),	Alternative splicing
  		member
  3
  NM_003791	MBTPS1	membrane-bound	Hydrolase, Protease, Serine	2546	6514
  		transcription factor	protease, Lipid metabolism,
  		protease,site 1	Cholesterol metabolism, Signal,
  			Transmembrane, Endoplasmic
  			reticulum, Golgi stack, Zymogen,
  			Autocatalytic cleavage, Glycoprotein,
  			Calcium
  NM_003796	C19orf2	chromosome 19	Nuclear protein	2547	6515
  		open reading frame 2
  NM_003801	GPAA1	GPAA1P anchor	Hypothetical protein	2548	6516
  		attachment protein 1
  		homolog (yeast)
  NM_003805	CRADD	CASP2 and RIPK1	Apoptosis, 3D-structure	2549	6517
  		domain containing
  		adaptor with death
  		domain
  NM_003807	TNFSF14	tumor necrosis factor	Cytokine, Transmembrane,	2550	6518
  		(ligand) superfamily,	Glycoprotein, Signal-anchor,
  		member 14	Alternative splicing
  NM_003808	TNFSF13	tumor necrosis factor	Cytokine, Immune response,	2551	6519
  		(ligand) superfamily,	Glycoprotein,Alternative splicing
  		member
  13
  NM_003815	ADAM15	a disintegrin and	Hydrolase, Metalloprotease, Zinc,	2552	6520
  		metalloproteinase	Signal, Glycoprotein, Zymogen,
  		domain 15	Transmembrane, EGF-like domain,
  		(metargidin)	SH3-binding, Phosphorylation
  NM_003820	TNFRSF14	tumor necrosis factor	Receptor, Transmembrane,	2553	6521
  		receptor superfamily,	Glycoprotein, Repeat, Signal,
  		member 14	Polymorphism, 3D-structure
  		(herpesvirus entry
  		mediator)
  NM_003829	MPDZ	multiple PDZ domain	Hypothetical protein	2554	6522
  		protein
  NM_003830	SIGLEC5	sialic acid binding Ig-	Cell adhesion, Lectin,	2555	6523
  		likelectin 5	Transmembrane, Signal,
  			Glycoprotein, Immunoglobulin
  			domain, Repeat, Antigen,
  			Polymorphism
  NM_003841	TNFRSF10C	tumor necrosis factor	Receptor, Apoptosis, Glycoprotein,	2556	6524
  		receptor superfamily,	Repeat, GPI-anchor, Signal,
  		member 10c, decoy	Lipoprotein
  		without an
  		intracellular domain
  NM_003846	PEX11B	peroxisomal		2557	6525
  		biogenesis factor
  		11B
  NM_003852	TIF1	transcriptional	Elongation factor, Protein	2558	6526
  		intermediary factor 1	biosynthesis, GTP-binding,
  			Methylation, Multigene family,
  			Transcription regulation, Repressor,
  			DNA-binding, Bromodomain, Zinc-
  			finger, Alternative splicing, Nuclear
  			protein, Coiled coil, Repeat
  NM_003853	IL18RAP	interleukin 18	Receptor	2559	6527
  		receptor accessory
  		protein
  NM_003866	INPP4B	inositol	Hypothetical protein	2560	6528
  		polyphosphate-4-
  		phosphatase, type II,
  		105 kDa
  NM_003877	SOCS2	suppressor of	SH2 domain, Growth regulation,	2561	6529
  		cytokine signaling 2	Signal transduction inhibitor
  NM_003887	DDEF2	development and	Hypothetical protein, ANK repeat,	2562	6530
  		differentiation	Repeat, SH3domain
  		enhancing factor
  2
  NM_003893	LDB1	LIM domain binding 1	DNA-binding, Homeobox, Nuclear	2563	6531
  			protein
  NM_003895	SYNJ1	synaptojanin	1	Hydrolase, Alternative splicing,	2564	6532
  			Repeat, Endocytosis, RNA-binding,
  			Multigene family, Hypothetical
  			protein
  NM_003896	SIAT9	sialyltransferase 9	Transferase, Glycosyltransferase,	2565	6533
  		(CMP-	Glycoprotein, Transmembrane,
  		NeuAc:lactosylceramide	Signal-anchor, Golgi stack
  		alpha-2,3-
  		sialyltransferase;
  		GM3 synthase)
  NM_003897	IER3	immediate early	Glycoprotein, Transmembrane,	2566	6534
  		response 3	Signal-anchor
  NM_003899	ARHGEF7	Rho guanine	Hypothetical protein, SH3 domain,	2567	6535
  		nucleotide exchange	Guanine-nucleotide releasing factor,
  		factor (GEF) 7	Alternative splicing, 3D-structure
  NM_003900	SQSTM1	sequestosome	1	Hypothetical protein	2568	6536
  NM_003903	CDC16	CDC16 cell division	Ubl conjugation pathway, Cell cycle,	2569	6537
  		cycle 16 homolog (S. cerevisiae)	Cell division, Mitosis, Repeat, TPR
  			repeat, Alternative splicing
  NM_003904	ZNF259	zinc finger protein	Nuclear protein, Zinc-finger	2570	6538
  		259
  NM_003905	APPBP1	amyloid beta	Hypothetical protein	2571	6539
  		precursorprotein
  		binding protein
  1,
  		59 kDa
  NM_003909	CPNE3	copine III	Repeat, Phosphorylation,	2572	6540
  			Transferase, Serine/threonine-
  			protein kinase
  NM_003915	CPNE1	copine I	Repeat	2573	6541
  NM_003923	FOXH1	forkhead box H1	Transcription regulation, Activator,	2574	6542
  			DNA-binding, Nuclear protein,
  			Polymorphism
  NM_003931	WASF1	WAS protein family,	Actin-binding	2575	6543
  		member 1
  NM_003938	AP3D1	adaptor-related	Golgi stack, Protein transport,	2576	6544
  		protein complex 3,	Transport, Alternative splicing,
  		delta 1 subunit	Polymorphism
  NM_003940	USP13	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	2577	6545
  		protease 13	Thiol protease, Multigene family,
  		(isopeptidase T-3)	Repeat, Hypothetical protein
  NM_003943	GENX-	genethonin 1		2578	6546
  	3414
  NM_003945	ATP6V0E	ATPase, H+	Hydrolase, Hydrogen ion transport,	2579	6547
  		transporting,	Transmembrane
  		lysosomal 9 kDa, V0
  		subunit e
  NM_003951	SLC25A14	solute carrier family	Mitochondrion, Repeat,	2580	6548
  		25 (mitochondrial	Transmembrane, Transport,
  		carrier, brain),	Alternative splicing
  		member 14
  NM_003953	MPZL1	myelin protein zero-	Hypothetical protein	2581	6549
  		like 1
  NM_003954	MAP3K14	mitogen-activated	Hypothetical protein, Transferase,	2582	6550
  		protein kinase	Serine/threonine-protein kinase,
  		kinase kinase 14	ATP-binding, Phosphorylation
  NM_003967	PNR	putative	G-protein coupled receptor,	2583	6551
  		neurotransmitter	Receptor, Transmembrane
  		receptor
  NM_003975	SH2D2A	SH2 domain protein	Angiogenesis, Phosphorylation, SH2	2584	6552
  		2A	domain, SH3-binding, Alternative
  			splicing
  NM_003977	AIP	aryl hydrocarbon	Repeat, TPR repeat	2585	6553
  		receptor interacting
  		protein
  NM_003978	PSTPIP1	proline-serine-	SH3 domain	2586	6554
  		threonine
  		phosphatase
  		interacting protein 1
  NM_003983	SLC7A6	solute carrier family	Hypothetical protein	2587	6555
  		7 (cationic amino
  		acid transporter, y+
  		system), member 6
  NM_004031	IRF7	interferon regulatory	Transcription regulation, DNA-	2588	6556
  		factor 7	binding, Nuclear protein, Activator,
  			Alternative splicing, Collagen
  NM_004033	ANXA6	annexin A6	Annexin, Calcium/phospholipid-	2589	6557
  			binding, Repeat, Acetylation,
  			Phosphorylation, 3D-structure
  NM_004037	AMPD2	adenosine	Hydrolase, Nucleotide metabolism,	2590	6558
  		monophosphate	Multigene family, Alternative splicing
  		deaminase 2
  		(isoform L)
  NM_004039	ANXA2	annexin A2	Annexin, Calcium, Calcium-binding,	2591	6559
  			Calcium/phospholipid-binding,
  			Repeat, Phosphorylation,
  			Acetylation, Polymorphism
  NM_004044	ATIC	5-aminoimidazole-4-	Purine biosynthesis, Transferase,	2592	6560
  		carboxamide	Hydrolase, Multifunctional enzyme
  		ribonucleotide
  		formyltransferase/IMP
  		cyclohydrolase
  NM_004046	ATP5A1	ATP synthase, H+	ATP synthesis, ATP-binding, CF(1),	2593	6561
  		transporting,	Hydrogen ion transport, Hydrolase,
  		mitochondrial F1	Ion transport, Transport,
  		complex, alpha	Mitochondrion, Transit peptide,
  		subunit, isoform 1,	Pyrrolidone carboxylic acid,
  		cardiac muscle	Hypothetical protein
  NM_004047	ATP6V0B	ATPase, H+	Hydrolase, Hydrogen ion transport,	2594	6562
  		transporting,	ATP synthesis, Transmembrane
  		lysosomal 21 kDa,
  		V0 subunit c″
  NM_004049	BCL2A1	BCL2-related protein	Apoptosis	2595	6563
  		A1
  NM_004053	BYSL	bystin-like	Cell adhesion	2596	6564
  NM_004054	C3AR1	complement	G-protein coupled receptor,	2597	6565
  		component 3a	Transmembrane, Glycoprotein,
  		receptor 1	Chemotaxis
  NM_004060	CCNG1	cyclin G1	Cyclin, Cell cycle, Cell division,	2598	6566
  			Mitosis, Nuclear protein
  NM_004070	CLCNKA	chloride channel Ka	Ionic channel, Ion transport, Chloride	2599	6567
  			channel, Chloride, Voltage-gated
  			channel, Transmembrane, CBS
  			domain, Repeat
  NM_004073	CNK	cytokine-inducible	Transferase, Serine/threonine-	2600	6568
  		kinase	protein kinase, ATP-binding, Repeat,
  			Phosphorylation, Hypothetical
  			protein, Kinase
  NM_004079	CTSS	cathepsin S	Hydrolase, Thiol protease,	2601	6569
  			Lysosome, Zymogen, Signal, 3D-
  			structure
  NM_004084	DEFA1	defensin, alpha 1,	Defensin, Antibiotic, Antiviral,	2602	6570
  		myeloid-related	Fungicide, Signal, 3D-structure
  		sequence
  NM_004090	DUSP3	dual specificity	Hydrolase, 3D-structure,	2603	6571
  		phosphatase 3	Hypothetical protein
  		(vaccinia virus
  		phosphatase VH1-
  		related)
  NM_004092	ECHS1	enoyl Coenzyme A	Fatty acid metabolism, Lyase,	2604	6572
  		hydratase, short	Mitochondrion, Transit peptide
  		chain, 1,
  		mitochondrial
  NM_004094	EIF2S1	eukaryotic	Initiation factor, Protein biosynthesis,	2605	6573
  		translation initiation	Translation regulation, RNA-binding,
  		factor 2, subunit 1	Phosphorylation, 3D-structure
  		alpha, 35 kDa
  NM_004099	STOM	stomatin	Erythrocyte, Transmembrane,	2606	6574
  			Phosphorylation, Lipoprotein,
  			Palmitate, Hypothetical protein,
  			Transducer, Prenylation, Multigene
  			family
  NM_004105	EFEMP1	EGF-containing	Repeat, EGF-like domain, Calcium-	2607	6575
  		fibulin-like	binding, Glycoprotein, Signal,
  		extracellular matrix	Disease mutation, Polymorphism,
  		protein 1	Alternative splicing
  NM_004106	FCER1G	Fc fragment of IgE,	IgE-binding protein, Receptor,	2608	6576
  		high affinity I,	Transmembrane, Signal
  		receptor for; gamma
  		polypeptide
  NM_004107	FCGRT	Fc fragment of IgG,	IgG-binding protein, Receptor,	2609	6577
  		receptor, transporter,	Transmembrane, Glycoprotein,
  		alpha	Signal, Immunoglobulin domain, 3D-
  			structure
  NM_004108	FCN2	ficolin	Lectin, Collagen, Repeat,	2610	6578
  		(collagen/fibrinogen	Glycoprotein, Signal, Multigene
  		domain containing	family
  		lectin) 2 (hucolin)
  NM_004109	FDX1	ferredoxin 1	Metal-binding, Iron-sulfur, Iron, 2Fe—2S,	2611	6579
  			Electron transport,
  			Mitochondrion, Transit peptide
  NM_004115	FGF14	fibroblast growth	Growth factor	2612	6580
  		factor 14
  NM_004119	FLT3	fms-related tyrosine	Signal, Transferase, Tyrosine-	2613	6581
  		kinase 3	protein kinase, Receptor,
  			Transmembrane, Glycoprotein,
  			Phosphorylation, ATP-binding,
  			Immunoglobulin domain
  NM_004122	GHSR	growth hormone	G-protein coupled receptor,	2614	6582
  		secretagogue	Transmembrane, Glycoprotein,
  		receptor	Alternative splicing
  NM_004126	GNG11	guanine nucleotide	Transducer, Prenylation, Lipoprotein,	2615	6583
  		binding protein (G	Multigene family
  		protein), gamma 11
  NM_004128	GTF2F2	general transcription	Transcription regulation, DNA-	2616	6584
  		factor IIF,	binding, Helicase, ATP-binding,
  		polypeptide 2,	Nuclear protein, 3D-structure
  		30 kDa
  NM_004130	GYG	glycogenin	Transferase, Glycogen biosynthesis,	2617	6585
  			Acetylation, Phosphorylation,
  			Glycoprotein, Alternative splicing,
  			Hypothetical protein
  NM_004131	GZMB	granzyme B	Hydrolase, Serine protease,	2618	6586
  		(granzyme 2,	Zymogen, Signal, T-cell, Cytolysis,
  		cytotoxic T-	Apoptosis, Glycoprotein, 3D-
  		lymphocyte-	structure, Protease
  		associated serine
  		esterase 1)
  NM_004134	HSPA9B	heat shock 70 kDa	ATP-binding, Heat shock,	2619	6587
  		protein 9B (mortalin-	Chaperone, Mitochondrion, Transit
  		2)	peptide
  NM_004147	DRG1	developmentally	GTP-binding, Hypothetical protein	2620	6588
  		regulated GTP
  		binding protein 1
  NM_004148	NINJ1	ninjurin 1	Cell adhesion, Transmembrane,	2621	6589
  			Hypothetical protein
  NM_004152	OAZ1	ornithine		2622	6590
  		decarboxylase
  		antizyme 1
  NM_004168	SDHA	succinate	Tricarboxylic acid cycle,	2623	6591
  		dehydrogenase	Flavoprotein, FAD, Oxidoreductase,
  		complex, subunit A,	Electron transport, Mitochondrion,
  		flavoprotein (Fp)	Transit peptide, Disease mutation,
  			Leigh syndrome
  NM_004177	STX3A	syntaxin 3A	Neurotransmitter transport, Coiled	2624	6592
  			coil, Transmembrane, Alternative
  			splicing
  NM_004178	TARBP2	TAR (HIV) RNA	Hypothetical protein, RNA-binding,	2625	6593
  		binding protein 2	Repeat, Nuclear protein
  NM_004180	TANK	TRAF family	Zinc-finger, Metal-binding,	2626	6594
  		member-associated	Alternative splicing, 3D-structure
  		NFKB activator
  NM_004183	VMD2	vitelliform macular	Transport, Ion transport, Ionic	2627	6595
  		dystrophy (Best	channel, Chloride channel, Chloride,
  		disease, bestrophin)	Calcium, Alternative splicing,
  			Disease mutation, Polymorphism,
  			Vision, Transmembrane,
  			Phosphorylation, Iron storage, Metal-
  			binding, 3D-structure
  NM_004207	SLC16A3	solute carrier family	Transport, Symport,	2628	6596
  		16 (monocarboxylic	Transmembrane, Multigene family
  		acid transporters),
  		member 3
  NM_004221	NK4	natural killer cell	Signal	2629	6597
  		transcript 4
  NM_004225	MFHAS1	malignant fibrous	GTP-binding	2630	6598
  		histiocytoma
  		amplified sequence 1
  NM_004235	KLF4	Kruppel-like factor 4	Transcription regulation, Activator,	2631	6599
  		(gut)	Zinc-finger, Metal-binding, DNA-
  			binding, Nuclear protein, Repeat
  NM_004239	TRIP11	thyroid hormone	Hypothetical protein, Antigen, Golgi	2632	6600
  		receptor interactor	stack, Coiled coil, Chromosomal
  		11	translocation
  NM_004244	CD163	CD163 antigen	Signal, Antigen	2633	6601
  NM_004245	TGM5	transglutaminase 5	Transferase, Acyltransferase,	2634	6602
  			Calcium-binding, Polymorphism,
  			Alternative splicing
  NM_004252	SLC9A3R1	solute carrier family		2635	6603
  		9 (sodium/hydrogen
  		exchanger), isoform
  		3 regulatory factor 1
  NM_004255	COX5A	cytochrome c	Oxidoreductase, Heme,	2636	6604
  		oxidase subunit Va	Mitochondrion, Inner membrane,
  			Transit peptide
  NM_004258	IGSF2	immunoglobulin		2637	6605
  		superfamily, member 2
  NM_004263	SEMA4F	sema domain,	Signal, Transmembrane,	2638	6606
  		immunoglobulin	Immunoglobulin domain, Multigene
  		domain (Ig),	family, Neurogenesis,
  		transmembrane	Developmental protein,
  		domain (TM) and	Glycoprotein, Alternative splicing
  		short cytoplasmic
  		domain,
  		(semaphorin) 4F
  NM_004265	FADS2	fatty acid desaturase 2	Hypothetical protein, Heme	2639	6607
  NM_004272	HOMER1	homer homolog 1	Coiled coil, Alternative splicing	2640	6608
  		(Drosophila)
  NM_004279	PMPCB	peptidase	Chaperone, Nuclear protein,	2641	6609
  		(mitochondrial	Phosphorylation, Hydrolase,
  		processing) beta	Metalloprotease, Zinc,
  			Mitochondrion, Transit peptide,
  			Hypothetical protein
  NM_004295	TRAF4	TNF receptor-	Apoptosis, Developmental protein,	2642	6610
  		associated factor 4	Nuclear protein, Zinc-finger, Coiled
  			coil, Repeat, Alternative splicing
  NM_004300	ACP1	acid phosphatase 1,	Hydrolase, Acetylation, Alternative	2643	6611
  		soluble	splicing, Polymorphism, 3D-structure
  NM_004305	BIN1	bridging integrator 1	Alternative splicing, SH3 domain,	2644	6612
  			Coiled coil, Endocytosis, Anti-
  			oncogene, Differentiation,
  			Phosphorylation, Hypothetical
  			protein
  NM_004309	ARHGDIA	Rho GDP	GTPase activation, 3D-structure	2645	6613
  		dissociation inhibitor
  		(GDI) alpha
  NM_004313	ARRB2	arrestin, beta 2	Sensory transduction, Nuclear	2646	6614
  			protein, Alternative splicing
  NM_004331	BNIP3L	BCL2/adenovirus	Apoptosis, Transmembrane,	2647	6615
  		E1B 19 kDa	Mitochondrion
  		interacting protein 3-
  		like
  NM_004334	BST1	bone marrow	Hydrolase, NAD, Glycoprotein, GPI-	2648	6616
  		stromal cell antigen 1	anchor, Signal, 3D-structure,
  			Lipoprotein, Hypothetical protein
  NM_004336	BUB1	BUB1 budding	Transferase, Serine/threonine-	2649	6617
  		uninhibited by	protein kinase, ATP-binding, Cell
  		benzimidazoles 1	cycle, Nuclear protein, Mitosis,
  		homolog (yeast)	Phosphorylation, Polymorphism
  NM_004337	C8orf1	chromosome 8 open	Meiosis	2650	6618
  		reading frame 1
  NM_004345	CAMP	cathelicidin	Antibiotic, Signal, Pyrrolidone	2651	6619
  		antimicrobial peptide	carboxylic acid
  NM_004350	RUNX3	runt-related	Transcription regulation, DNA-	2652	6620
  		transcription factor 3	binding, Nuclear protein, ATP-
  			binding, Alternative splicing
  NM_004358	CDC25B	cell division cycle	Cell division, Mitosis, Hydrolase,	2653	6621
  		25B	Alternative splicing, Multigene family,
  			3D-structure
  NM_004360	CDH1	cadherin	1,type 1,	Elongation factor, Protein	2654	6622
  		E-cadherin	biosynthesis, GTP-binding,
  		(epithelial)	Methylation, Multigene family,
  			Ribosomal protein, Repeat,
  			Hypothetical protein, Cell adhesion,
  			Glycoprotein, Transmembrane,
  			Calcium-binding, Signal,
  			Phosphorylation, Disease mutation,
  			Polymorphism, 3D-structure
  NM_004368	CNN2	calponin	2	Calmodulin-binding, Actin-binding,	2655	6623
  			Multigene family, Repeat
  NM_004374	COX6C	cytochrome c	Oxidoreductase, Inner membrane,	2656	6624
  		oxidase subunit VIc	Mitochondrion
  NM_004375	COX11	COX11 homolog,	Copper, Mitochondrion,	2657	6625
  		cytochrome c	Transmembrane, Transit peptide,
  		oxidase assembly	Transport, Protein transport, SH3-
  		protein (yeast)	binding, Membrane, Golgi stack,
  			Phosphorylation, Hypothetical
  			protein
  NM_004380	CREBBP	CREB binding	Transferase, Transcription	2658	6626
  		protein (Rubinstein-	regulation, Nuclear protein,
  		Taybi syndrome)	Activator, Bromodomain,
  			Chromosomal translocation, Zinc-
  			finger, Repeat, Disease mutation,
  			3D-structure
  NM_004381	CREBL1	cAMP responsive	Glycoprotein, Cell adhesion, Repeat,	2659	6627
  		element binding	EGF-like domain, Coiled coil,
  		protein-like 1	Extracellular matrix, Alternative
  			splicing, Signal, Ehlers-Danlos
  			syndrome, Transcription regulation,
  			DNA-binding, Activator, Unfolded
  			protein response, Nuclear protein,
  			Endoplasmic reticu
  NM_004385	CSPG2	chondroitin sulfate	Glycoprotein, Proteoglycan, Lectin,	2660	6628
  		proteoglycan 2	Extracellular matrix, Sushi, Signal,
  		(versican)	Repeat, EGF-like domain, Calcium,
  			Immunoglobulin domain, Hyaluronic
  			acid, Alternative splicing
  NM_004390	CTSH	cathepsin H	Hydrolase, Protease, Thiol protease,	2661	6629
  			Lysosome, Glycoprotein, Zymogen,
  			Signal, 3D-structure
  NM_004398	DDX10	DEAD (Asp-Glu-Ala-	Helicase, ATP-binding, RNA-binding	2662	6630
  		Asp)box polypeptide
  		10
  NM_004409	DMPK	dystrophia	Transferase, Serine/threonine-	2663	6631
  		myotonica-protein	protein kinase, ATP-binding, Coiled
  		kinase	coil, Alternative splicing
  NM_004417	DUSP1	dual specificity	Hydrolase, Cell cycle	2664	6632
  		phosphatase 1
  NM_004418	DUSP2	dual specificity	Hydrolase, Nuclear protein, 3D-	2665	6633
  		phosphatase 2	structure
  NM_004424	E4F1	E4F transcription	Metal-binding, Zinc, Zinc-finger	2666	6634
  		factor 1
  NM_004427	PHC2	polyhomeotic-like 2	Hypothetical protein	2667	6635
  		(Drosophila)
  NM_004446	EPRS	glutamyl-prolyl-tRNA	Aminoacyl-tRNA synthetase, Protein	2668	6636
  		synthetase	biosynthesis, Ligase, ATP-binding,
  			Multifunctional enzyme, Repeat, 3D-
  			structure
  NM_004450	ERH	enhancer of		2669	6637
  		rudimentary
  		homolog
  		(Drosophila)
  NM_004453	ETFDH	electron-transferring-	Oxidoreductase, Electron transport,	2670	6638
  		flavoprotein	Flavoprotein, FAD, Iron-sulfur, 4Fe—4S,
  		dehydrogenase	Mitochondrion, Transit peptide,
  			Ubiquinone, Transmembrane,
  			Glutaricaciduria
  NM_004475	FLOT2	flotillin	2	Cell adhesion, Membrane	2671	6639
  NM_004477	FRG1	FSHD region gene 1	Multigene family	2672	6640
  NM_004479	FUT7	fucosyltransferase 7	Transferase, Glycosyltransferase,	2673	6641
  		(alpha (1,3)	Transmembrane, Glycoprotein,
  		fucosyltransferase)	Signal-anchor, Golgi stack
  NM_004480	FUT8	fucosyltransferase 8	Transferase, Glycosyltransferase,	2674	6642
  		(alpha (1,6)	Transmembrane, Signal-anchor,
  		fucosyltransferase)	Golgi stack, SH3 domain, SH3-
  			binding, Alternative splicing
  NM_004482	GALNT3	UDP-N-acetyl-alpha-	Transferase	2675	6643
  		D-
  		galactosamine:polypeptide
  		N-
  		acetylgalactosaminyl
  		transferase 3
  		(GalNAc-T3)
  NM_004483	GCSH	glycine cleavage	Mitochondrion, Transit peptide,	2676	6644
  		system protein H	Lipoyl
  		(aminomethyl
  		carrier)
  NM_004485	GNG4	guanine nucleotide	Transducer, Prenylation, Lipoprotein,	2677	6645
  		binding protein (G	Multigene family
  		protein),gamma 4
  NM_004489	GPS2	G protein pathway	Hypothetical protein	2678	6646
  		suppressor 2
  NM_004492	GTF2A2	general transcription	Transcription regulation, Nuclear	2679	6647
  		factor IIA, 2, 12 kDa	protein
  NM_004497	FOXA3	forkhead box A3	DNA-binding, Nuclear protein,	2680	6648
  			Transcription regulation, Activator,
  			Polymorphism
  NM_004504	HRB	HIV-1 Rev binding	Nuclear protein, Transport, Repeat,	2681	6649
  		protein	DNA-binding, Zinc-finger
  NM_004506	HSF2	heat shock	Heat shock, Transcription regulation,	2682	6650
  		transcription factor 2	Nuclear protein, DNA-binding,
  			Activator, Phosphorylation,
  			Multigene family
  NM_004513	IL16	interleukin 16	Cytokine, Chemotaxis, Repeat, 3D-	2683	6651
  		(lymphocyte	structure
  		chemoattractant
  		factor)
  NM_004515	ILF2	interleukin enhancer		2684	6652
  		binding factor 2,
  		45 kDa
  NM_004516	ILF3	interleukin enhancer	Hypothetical protein, Transcription	2685	6653
  		bindingfactor 3,	regulation, DNA-binding, RNA-
  		90 kDa	binding, Nuclear protein, Repeat,
  			Phosphorylation, Methylation,
  			Alternative splicing
  NM_004524	LLGL2	lethal giant larvae	Repeat, WD repeat	2686	6654
  		homolog 2
  		(Drosophila)
  NM_004529	MLLT3	myeloid/lymphoid or	Transcription regulation, Activator,	2687	6655
  		mixed-lineage	Nuclear protein, Chromosomal
  		leukemia (trithorax	translocation, Proto-oncogene
  		homolog,
  		Drosophila);
  		translocated to, 3
  NM_004537	NAP1L1	nucleosome	Nuclear protein	2688	6656
  		assembly protein 1-
  		like 1
  NM_004554	NFATC4	nuclear factor of	Hypothetical protein, Transcription	2689	6657
  		activated T-cells,	regulation, Activator, Nuclear
  		cytoplasmic,	protein, DNA-binding, Repeat,
  		calcineurin-	Phosphorylation
  		dependent 4
  NM_004563	PCK2	phosphoenolpyruvate	Gluconeogenesis, Lyase,	2690	6658
  		carboxykinase 2	Decarboxylase, GTP-binding,
  		(mitochondrial)	Mitochondrion, Transit peptide,
  			Manganese
  NM_004566	PFKFB3	6-phosphofructo-2-	Kinase, Hydrolase, Multifunctional	2691	6659
  		kinase/fructose-2,6-	enzyme, Transferase, ATP-binding,
  		biphosphatase 3	Phosphorylation, Multigene family,
  			Alternative splicing
  NM_004569	PIGH	phosphatidylinositol	Hypothetical protein, Transferase,	2692	6660
  		glycan, class H	Glycosyltransferase
  NM_004573	PLCB2	phospholipase C,	Hydrolase, Lipid degradation,	2693	6661
  		beta 2	Transducer, Calcium
  NM_004578	RAB4A	RAB4A, member	GTP-binding, Lipoprotein,	2694	6662
  		RAS oncogene	Prenylation, Protein transport,
  		family	Phosphorylation
  NM_004580	RAB27A	RAB27A, member	GTP-binding, Lipoprotein,	2695	6663
  		RAS oncogene	Prenylation, Alternative splicing,
  		family	Disease mutation
  NM_004583	RAB5C	RAB5C, member	GTP-binding, Lipoprotein,	2696	6664
  		RAS oncogene	Prenylation, Protein transport
  		family
  NM_004603	STX1A	syntaxin 1A (brain)	Neurotransmitter transport, Coiled	2697	6665
  			coil, Transmembrane, Antigen,
  			Alternative splicing, Williams-Beuren
  			syndrome
  NM_004618	TOP3A	topoisomerase	Isomerase, Topoisomerase, DNA-	2698	6666
  		(DNA) III alpha	binding, Repeat, Zinc-finger,
  			Alternative splicing, Polymorphism
  NM_004629	FANCG	Fanconi anemia,	DNA repair, Nuclear protein	2699	6667
  		complementation
  		group G
  NM_004632	DAP3	death associated	Apoptosis, Ribosomal protein,	2700	6668
  		protein 3	Mitochondrion
  NM_004633	IL1R2	interleukin 1	Immunoglobulin domain, Receptor,	2701	6669
  		receptor, type II	Glycoprotein, Transmembrane,
  			Signal, Repeat
  NM_004635	MAPKAPK3	mitogen-activated	ATP-binding, Kinase,	2702	6670
  		protein kinase-	Serine/threonine-protein kinase,
  		activated protein	Transferase
  		kinase 3
  NM_004637	RAB7	RAB7, member RAS	GTP-binding, Lipoprotein,	2703	6671
  		oncogene family	Prenylation, Protein transport,
  			Hypothetical protein
  NM_004642	CDK2AP1	CDK2-associated	Anti-oncogene	2704	6672
  		protein 1
  NM_004648	PTPNS1	protein tyrosine	Repeat, Signal, Transmembrane,	2705	6673
  		phosphatase, non-	Immunoglobulin domain, SH3-
  		receptor type	binding, Glycoprotein,
  		substrate 1	Phosphorylation, Alternative splicing,
  			Polymorphism
  NM_004651	USP11	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	2706	6674
  		protease 11	Thiol protease, Nuclear protein,
  			Multigene family
  NM_004664	LIN7A	lin-7 homolog A (C. elegans)		2707	6675
  NM_004665	VNN2	vanin	2	Hydrolase, Signal, Glycoprotein,	2708	6676
  			GPI-anchor, Lipoprotein
  NM_004666	VNN1	vanin	1	Hydrolase, Signal, Glycoprotein,	2709	6677
  			GPI-anchor, Lipoprotein
  NM_004668	MGAM	maltase-	Multifunctional enzyme,	2710	6678
  		glucoamylase	Transmembrane, Glycoprotein,
  		(alpha-glucosidase)	Hydrolase, Glycosidase, Repeat,
  			Signal-anchor, Sulfation
  NM_004682	PSIP2	PC4 and SFRS1		2711	6679
  		interactingprotein 1
  NM_004689	MTA1	metastasis	Zinc-finger, Nuclear protein,	2712	6680
  		associated 1	Alternative splicing
  NM_004694	SLC16A6	solute carrier family	Transport, Symport,	2713	6681
  		16 (monocarboxylic	Transmembrane, Multigene family
  		acid transporters),
  		member 6
  NM_004706	ARHGEF1	Rho guanine	Guanine-nucleotide releasing factor,	2714	6682
  		nucleotide exchange	GTPase activation, Coiled coil,
  		factor (GEF) 1	Alternative splicing, Phosphorylation,
  			3D-structure
  NM_004708	PDCD5	programmed cell	Apoptosis	2715	6683
  		death 5
  NM_004712	HGS	hepatocyte growth	Kinase	2716	6684
  		factor-regulated
  		tyrosine kinase
  		substrate
  NM_004720	EDG4	endothelial	G-protein coupled receptor,	2717	6685
  		differentiation,	Transmembrane, Glycoprotein,
  		lysophosphatidic	Multigene family, Lipoprotein,
  		acid G-protein-	Palmitate
  		coupled receptor, 4
  NM_004726	REPS2	RALBP1 associated	Calcium-binding, Coiled coil,	2718	6686
  		Eps domain	Phosphorylation, Alternative splicing,
  		containing 2	Repeat, 3D-structure
  NM_004727	SLC24A1	solute carrier family	Vision, Transport, Antiport, Symport,	2719	6687
  		24	Calcium transport, Transmembrane,
  		(sodium/potassium/calcium	Glycoprotein, Phosphorylation,
  		exchanger),	Signal, Repeat,Alternative splicing
  		member
  1
  NM_004729	ALTE	Ac-like transposable		2720	6688
  		element
  NM_004741	NOLC1	nucleolar and coiled-	Nuclear protein, Phosphorylation,	2721	6689
  		body phosphoprotein 1	Repeat, GTP-binding, ATP-binding,
  			Alternative splicing
  NM_004748	CPR8	cell cycle	Hypothetical protein	2722	6690
  		progression 8
  		protein
  NM_004749	CPR2	cell cycle	Hypothetical protein	2723	6691
  		progression 2
  		protein
  NM_004756	NUMBL	numb homolog		2724	6692
  		(Drosophila)-like
  NM_004757	SCYE1	small inducible	Protein biosynthesis, RNA-binding,	2725	6693
  		cytokine subfamily	tRNA-binding, Cytokine, 3D-
  		E,member 1	structure
  		(endothelial
  		monocyte-activating)
  NM_004762	PSCD1	pleckstrin homology,	Guanine-nucleotide releasing factor,	2726	6694
  		Sec7 and coiled-coil	Coiled coil, Alternative splicing, 3D-
  		domains 1(cytohesin	structure
  		1)
  NM_004774	PPARBP	PPAR binding	DNA-binding, Transcription	2727	6695
  		protein	regulation, Activator, Repeat,
  			Nuclear protein, Alternative splicing
  NM_004779	CNOT8	CCR4-NOT	Coiled coil, Nuclear protein,	2728	6696
  		transcription	Alternative splicing, Hypothetical
  		complex,subunit 8	protein, Molybdenum cofactor
  			biosynthesis, Disease mutation,
  			Transcription regulation, Repressor
  NM_004781	VAMP3	vesicle-associated	Synapse, Synaptosome,	2729	6697
  		membrane protein 3	Transmembrane, Coiled coil,
  		(cellubrevin)	Multigene family
  NM_004786	TXNL	thioredoxin-like,	Redox-active center, Electron	2730	6698
  		32 kDa	transport, 3D-structure
  NM_004800	TM9SF2	transmembrane 9	Signal, Transmembrane	2731	6699
  		superfamily member 2
  NM_004802	OTOF	otoferlin	Transmembrane, Repeat, Alternative	2732	6700
  			splicing, Deafness
  NM_004808	NMT2	N-	Transferase, Acyltransferase	2733	6701
  		myristoyltransferase 2
  NM_004814	HPRP8BP	U5 snRNP-specific	Repeat, WD repeat, Hypothetical	2734	6702
  		40 kDa protein	protein
  		(hPrp8-binding)
  NM_004817	TJP2	tight junction protein	Tight junction, SH3 domain, Repeat,	2735	6703
  		2 (zona occludens 2)	Membrane, Alternative splicing,
  			Alternative promoter usage, Nuclear
  			protein, Phosphorylation
  NM_004834	MAP4K4	mitogen-activated	ATP-binding, Serine/threonine-	2736	6704
  		protein kinase	protein kinase, Transferase,
  		kinase kinase kinase 4	Alternative splicing
  NM_004848	C1orf38	chromosome 1 open	Hypothetical protein	2737	6705
  		reading frame 38
  NM_004854	CHST10	carbohydrate	Transferase	2738	6706
  		sulfotransferase 10
  NM_004856	KIF23	anaphase-promoting	Motor protein, Cell division,	2739	6707
  		complex subunit 7	Microtubule, ATP-binding, Coiled
  			coil, Mitosis, Cell cycle, Nuclear
  			protein
  NM_004862	LITAF	lipopolysaccharide-	Hypothetical protein, Transcription	2740	6708
  		induced TNF factor	regulation, Nuclear protein
  NM_004868	GPSN2	glycoprotein,	Transmembrane, Glycoprotein,	2741	6709
  		synaptic 2	Alternative splicing
  NM_004875	POLR1C	polymerase (RNA) I	Hypothetical protein, Transferase,	2742	6710
  		polypeptide C,	DNA-directed RNA polymerase,
  		30 kDa	Transcription, Nuclear protein,
  			Alternative splicing
  NM_004877	GMFG	glia maturation	Growth factor, Ribosomal protein	2743	6711
  		factor, gamma
  NM_004878	PTGES	prostaglandin E	Hypothetical protein,	2744	6712
  		synthase	Transmembrane
  NM_004879	EI24	etoposide induced		2745	6713
  		2.4 mRNA
  NM_004889	ATP5J2	ATP synthase, H+	ATP synthesis, Hydrogen ion	2746	6714
  		transporting,	transport, CF(0), Mitochondrion,
  		mitochondrial F0	Acetylation, Alternative splicing
  		complex, subunit f,
  		isoform 2
  NM_004900	APOBEC3B	apolipoprotein B	Hydrolase	2747	6715
  		mRNA editing
  		enzyme, catalytic
  		polypeptide-like 3B
  NM_004902	RNPC2	RNA-binding region	Transcription regulation, Activator,	2748	6716
  		(RNP1, RRM)	Nuclear protein, RNA-binding,
  		containing 2	mRNA processing, mRNA splicing,
  			Repeat, Alternative splicing,
  			Polymorphism
  NM_004905	PRDX6	peroxiredoxin	6	Hydrolase, Oxidoreductase,	2749	6717
  			Peroxidase, Lipid degradation,
  			Antioxidant, Redox-active center,
  			Multifunctional enzyme, Lysosome,
  			3D-structure
  NM_004907	ETR101	immediate early	ATP-binding, Coiled coil,	2750	6718
  		protein	Microtubules, Motor protein
  NM_004910	PITPNM1	phosphatidylinositol	Hypothetical protein	2751	6719
  		transfer protein,
  		membrane-
  		associated 1
  NM_004915	ABCG1	ATP-binding	ATP-binding, Transport, Hypothetical	2752	6720
  		cassette, sub-family	protein, Lipid transport,
  		G (WHITE),member 1	Transmembrane, Alternative
  			splicing, Polymorphism
  NM_004916	WWOX	Human	Oxidoreductase	2753	6721
  		oxidoreductase
  		(HHCMA56) mRNA,
  		complete cds.
  NM_004920	AATK	apoptosis-	Kinase, Hypothetical protein, ATP-	2754	6722
  		associated tyrosine	binding, Transferase
  		kinase
  NM_004924	ACTN4	actinin, alpha 4	Actin-binding, Calcium-binding,	2755	6723
  			Repeat, Multigene family, Disease
  			mutation, Nuclear protein,
  			Hypothetical protein
  NM_004928	C21orf2	chromosome 21	Alternative splicing, Polymorphism	2756	6724
  		open reading frame 2
  NM_004930	CAPZB	capping protein	Cytoskeleton, Actin-binding,	2757	6725
  		(actin filament)	Alternative splicing, Actin capping
  		muscle Z-line, beta
  NM_004939	DDX1	DEAD (Asp-Glu-Ala-	Hydrolase, ATP-binding, Helicase,	2758	6726
  		Asp) box polypeptide 1	RNA-binding
  NM_004945	DNM2	dynamin 2	Hydrolase, Motor protein, GTP-	2759	6727
  			binding, Microtubule, Multigene
  			family, Endocytosis, Alternative
  			splicing, Hypothetical protein
  NM_004954	MARK2	MAP/microtubule	ATP-binding, Kinase,	2760	6728
  		affinity-regulating	Serine/threonine-protein kinase,
  		kinase 2	Transferase
  NM_004974	KCNA2	potassium voltage-	Transport, Ion transport, Ionic	2761	6729
  		gated channel,	channel, Voltage-gated channel,
  		shaker-related	Potassium channel, Potassium
  		subfamily, member 2	transport, Potassium,
  			Transmembrane, Glycoprotein,
  			Phosphorylation, Multigene family
  NM_004979	KCND1	potassium voltage-	Transport, Ion transport, Ionic	2762	6730
  		gated channel, Shal-	channel, Voltage-gated channel,
  		related subfamily,	Potassium channel, Potassium
  		member 1	transport, Potassium,
  			Transmembrane, Multigene family
  NM_004994	MMP9	matrix	Hydrolase, Metalloprotease,	2763	6731
  		metalloproteinase 9	Glycoprotein, Zinc, Zymogen,
  		(gelatinase B, 92 kDa	Calcium, Collagen degradation,
  		gelatinase, 92 kDa	Extracellular matrix, Repeat, Signal,
  		type IV collagenase)	Polymorphism, 3D-structure
  NM_005000	NDUFA5	NADH	Hypothetical protein,	2764	6732
  		dehydrogenase	Oxidoreductase, NAD, Ubiquinone,
  		(ubiquinone) 1 alpha	Mitochondrion, Acetylation
  		subcomplex, 5,
  		13 kDa
  NM_005003	NDUFAB1	NADH	Fatty acid biosynthesis,	2765	6733
  		dehydrogenase	Phosphopantetheine, Mitochondrion,
  		(ubiquinone) 1,	Transit peptide, Oxidoreductase
  		alpha/beta
  		subcomplex, 1, 8 kDa
  NM_005009	NME4	non-metastatic cells	Transferase, Kinase, ATP-binding,	2766	6734
  		4, protein expressed	Mitochondrion, Transit peptide, 3D-
  		in	structure
  NM_005011	NRF1	nuclear respiratory	Transcription regulation, DNA-	2767	6735
  		factor 1	binding, Activator, Nuclear protein,
  			Phosphorylation, Alternative splicing
  NM_005022	PFN1	profilin 1	Actin-binding, Cytoskeleton,	2768	6736
  			Multigene family, Acetylation, 3D-
  			structure
  NM_005024	SERPINB10	serine (or cysteine)	Serpin, Serine protease inhibitor	2769	6737
  		proteinase inhibitor,
  		clade B (ovalbumin),
  		member 10
  NM_005025	SERPINI1	serine (or cysteine)	Serpin, Serine protease inhibitor,	2770	6738
  		proteinase inhibitor,	Glycoprotein, Signal, Disease
  		clade I	mutation
  		(neuroserpin),
  		member 1
  NM_005026	PIK3CD	phosphoinositide-3-	Kinase, Transferase, Multigene	2771	6739
  		kinase, catalytic,	family
  		delta polypeptide
  NM_005029	PITX3	paired-like	Homeobox, DNA-binding,	2772	6740
  		homeodomain	Developmental protein, Nuclear
  		transcription factor 3	protein, Disease mutation
  NM_005030	PLK	polo-like kinase	Transferase, Serine/threonine-	2773	6741
  		(Drosophila)	protein kinase, ATP-binding, Repeat,
  			Nuclear protein, Phosphorylation
  NM_005040	PRCP	prolylcarboxypeptidase	Hydrolase, Carboxypeptidase,	2774	6742
  		(angiotensinase	Glycoprotein, Zymogen, Signal,
  		C)	Lysosome
  NM_005044	PRKX	protein kinase, X-	ATP-binding, Kinase,	2775	6743
  		linked	Serine/threonine-protein kinase,
  			Transferase, Tyrosine-protein
  			kinase, cAMP
  NM_005055	RAPSN	receptor-associated	Synapse, Postsynaptic membrane,	2776	6744
  		protein of the	Cytoskeleton, Phosphorylation,
  		synapse, 43 kD	Myristate, Zinc-finger, Repeat, TPR
  			repeat, Alternative splicing,
  			Lipoprotein, Metal-binding, Receptor
  NM_005056	RBBP2	retinoblastoma	Trans-acting factor, Nuclear protein,	2777	6745
  		binding protein 2	Repeat, Zinc-finger
  NM_005061	RPL3L	ribosomal protein	Ribosomal protein	2778	6746
  		L3-like
  NM_005066	SFPQ	splicing factor	Nuclear protein, RNA-binding, DNA-	2779	6747
  		proline/glutamine	binding, mRNA splicing, Repeat,
  		rich (polypyrimidine	Alternative splicing
  		tract binding protein
  		associated)
  NM_005084	PLA2G7	phospholipase A2,	Hydrolase, Lipid degradation,	2780	6748
  		group VII (platelet-	Glycoprotein, Signal, Polymorphism,
  		activating factor	Disease mutation
  		acetylhydrolase,
  		plasma)
  NM_005085	NUP214	nucleoporin 214 kDa	Hypothetical protein, Repeat, WD	2781	6749
  			repeat, Nuclear protein, Transport,
  			Proto-oncogene, Chromosomal
  			translocation, Glycoprotein
  NM_005091	PGLYRP	peptidoglycan	Antibiotic, Immune response, Signal	2782	6750
  		recognition protein
  NM_005096	ZNF261	zinc finger protein	Hypothetical protein, Chromosomal	2783	6751
  		261	translocation, Transmembrane,
  			Alternative splicing
  NM_005099	ADAMTS4	a disintegrin-like and	Hydrolase, Metalloprotease, Zinc,	2784	6752
  		metalloprotease	Signal, Glycoprotein, Zymogen,
  		(reprolysin type) with	Extracellular matrix, Hypothetical
  		thrombospondin type	protein
  		1 motif, 4
  NM_005106	DLEC1	deleted in lung and	Hypothetical protein	2785	6753
  		esophageal cancer 1
  NM_005111	CRYZL1	crystallin, zeta	Oxidoreductase, NADP, Alternative	2786	6754
  		(quinone reductase)-	splicing
  		like 1
  NM_005112	WDR1	WD repeat domain 1	Repeat, WD repeat, Hypothetical	2787	6755
  			protein, Actin-binding, Cytoskeleton,
  			Alternative splicing, Polymorphism
  NM_005134	PPP4R1	protein phosphatase	Hypothetical protein	2788	6756
  		4, regulatory subunit 1
  NM_005137	DGCR2	DiGeorge syndrome	Cell adhesion, Receptor, Signal,	2789	6757
  		critical region gene 2	Transmembrane, Lectin,
  			Glycoprotein
  NM_005139	ANXA3	annexin A3	Annexin, Calcium/phospholipid-	2790	6758
  			binding, Repeat, Phospholipase A2
  			inhibitor, 3D-structure,
  			Polymorphism
  NM_005143	HP	haptoglobin	Glycoprotein, Serine protease	2791	6759
  			homolog, Sushi, Hemoglobin-
  			binding, Signal, Repeat,
  			Polymorphism
  NM_005148	UNC119	unc-119 homolog (C. elegans)	Vision, Alternative splicing	2792	6760
  NM_005151	USP14	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	2793	6761
  		protease 14 (tRNA-	Thiol protease, Multigene family
  		guanine
  		transglycosylase)
  NM_005165	ALDOC	aldolase C, fructose-	Lyase, Schiff base, Glycolysis,	2794	6762
  		bisphosphate	Multigene family
  NM_005167	ARHC	hypothetical protein	DNA condensation, Mitosis, Cell	2795	6763
  		MGC19531	cycle, ATP-binding, Coiled coil,
  			Nuclear protein, Alternative splicing,
  			Hypothetical protein, Proto-
  			oncogene, GTP-binding, Prenylation,
  			Lipoprotein
  NM_005173	ATP2A3	ATPase, Ca++	Hydrolase, Calcium transport,	2796	6764
  		transporting,	Transmembrane, Phosphorylation,
  		ubiquitous	ATP-binding, Metal-binding,
  			Magnesium, Calcium-binding,
  			Multigene family, Alternative splicing
  NM_005174	ATP5C1	ATP synthase, H+	ATP synthesis, CF(1), Hydrogen ion	2797	6765
  		transporting,	transport, Hydrolase, Mitochondrion,
  		mitochondrial F1	Transit peptide, Alternative splicing,
  		complex, gamma	Hypothetical protein
  		polypeptide 1
  NM_005180	BMI1	B lymphoma Mo-	Chromatin regulator, Nuclear	2798	6766
  		MLV insertion region	protein, Transcription regulation,
  		(mouse)	Repressor, Zinc-finger, Proto-
  			oncogene
  NM_005185	CALML3	calmodulin-like 3	Calcium-binding, Repeat,	2799	6767
  			Methylation, 3D-structure
  NM_005190	CCNC	cyclin C	Cyclin, Cell cycle, Cell division,	2800	6768
  			Nuclear protein, Transcription
  			regulation
  NM_005195	CEBPD	KIAA0146 protein	Transcription regulation, Activator,	2801	6769
  			DNA-binding, Nuclear protein
  NM_005197	CHES1	checkpoint	Transcription regulation, Activator,	2802	6770
  		suppressor 1	DNA-binding, Nuclear protein,
  			Alternative splicing
  NM_005199	CHRNG	cholinergic receptor,	Receptor, Postsynaptic membrane,	2803	6771
  		nicotinic, gamma	Ionic channel, Glycoprotein, Signal,
  		polypeptide	Transmembrane
  NM_005213	CSTA	cystatin A (stefin A)	Thiol protease inhibitor, 3D-structure	2804	6772
  NM_005217	DEFA3	defensin, alpha 3,	Defensin, Antibiotic, Antiviral,	2805	6773
  		neutrophil-specific	Fungicide, Signal, 3D-structure
  NM_005224	DRIL1	dead ringer-like 1	Transcription regulation, Activator,	2806	6774
  		(Drosophila)	DNA-binding, Nuclear protein
  NM_005231	EMS1	ems1 sequence	Phosphorylation, Repeat, SH3	2807	6775
  		(mammary tumor	domain, Cytoskeleton
  		and squamous cell
  		carcinoma-
  		associated (p80/85
  		src substrate)
  NM_005239	ETS2	v-ets	Proto-oncogene, DNA-binding,	2808	6776
  		erythroblastosis	Nuclear protein
  		virus E26 oncogene
  		homolog 2 (avian)
  NM_005248	FGR	Gardner-Rasheed	Transferase, Tyrosine-protein	2809	6777
  		feline sarcoma viral	kinase, Proto-oncogene, ATP-
  		(v-fgr) oncogene	binding, Phosphorylation, SH2
  		homolog	domain, SH3 domain
  NM_005252	FOS	v-fos FBJ murine	Proto-oncogene, Nuclear protein,	2810	6778
  		osteosarcoma viral	Phosphorylation, DNA-binding, 3D-
  		oncogene homolog	structure
  NM_005253	FOSL2	FOS-like antigen 2	Nuclear protein, DNA-binding	2811	6779
  NM_005255	GAK	cyclin G associated	Transferase, Serine/threonine-	2812	6780
  		kinase	protein kinase, ATP-binding, Nuclear
  			protein, Endoplasmic reticulum, Cell
  			cycle
  NM_005256	GAS2	growth arrest-	Growth arrest, Phosphorylation,	2813	6781
  		specific 2	Apoptosis, Cell cycle, Cytoskeleton
  NM_005263	GFI1	growth factor	Transcription regulation, Zinc-finger,	2814	6782
  		independent 1	DNA-binding, Nuclear protein, Metal-
  			binding, Repeat, Disease mutation
  NM_005270	GLI2	GLI-Kruppel family	Transcription regulation, Zinc-finger,	2815	6783
  		member GLI2	Metal-binding, DNA-binding, Nuclear
  			protein, Repeat, Alternative splicing
  NM_005271	GLUD1	glutamate	Oxidoreductase, NADP,	2816	6784
  		dehydrogenase 1	Mitochondrion, Transit peptide,
  			Polymorphism, Disease mutation,
  			Multigene family, 3D-structure
  NM_005273	GNB2	guanine nucleotide	Transducer, Repeat, WD repeat,	2817	6785
  		binding protein (G	Multigene family
  		protein), beta
  		polypeptide 2
  NM_005274	GNG5	guanine nucleotide	Transducer, Prenylation, Lipoprotein,	2818	6786
  		binding protein (G	Multigene family
  		protein), gamma 5
  NM_005286	GPR8	G protein-coupled	Transcription regulation, Zinc-finger,	2819	6787
  		receptor 8	DNA-binding, Nuclear protein,
  			Repeat, G-protein coupled receptor,
  			Transmembrane, Glycoprotein,
  			Lipoprotein, Palmitate,
  			Phosphorylation, Polymorphism
  NM_005291	GPR17	G protein-coupled	G-protein coupled receptor,	2820	6788
  		receptor 17	Transmembrane, Glycoprotein,
  			Alternative splicing, Receptor
  NM_005327	HADHSC	L-3-hydroxyacyl-	Fatty acid metabolism,	2821	6789
  		Coenzyme A	Oxidoreductase, NAD,
  		dehydrogenase,	Mitochondrion, Transit peptide, 3D-
  		short chain	structure
  NM_005335	HCLS1	hematopoietic cell-	Repeat, SH3 domain,	2822	6790
  		specificLyn	Phosphorylation
  		substrate
  1
  NM_005340	HINT1	histidine triad	Hydrolase, Acetylation, 3D-structure	2823	6791
  		nucleotide binding
  		protein
  1
  NM_005345	HSPA1A	heat shock	70 kDa	ATP-binding, Chaperone, Heat	2824	6792
  		protein 1A	shock, Multigene family, 3D-
  			structure
  NM_005346	HSPA1B	heat shock 70 kDa	ATP-binding, Chaperone, Heat	2825	6793
  		protein 1B	shock, Multigene family, 3D-
  			structure
  NM_005357	LIPE	lipase, hormone-	Hydrolase, Lipid degradation,	2826	6794
  		sensitive	Phosphorylation
  NM_005358	LMO7	LIM domain only 7	LIM domain, Metal-binding, Zinc,	2827	6795
  			Hypothetical protein, Zinc-finger
  NM_005360	MAF	v-maf	Proto-oncogene, Transcription	2828	6796
  		musculoaponeurotic	regulation, DNA-binding, Nuclear
  		fibrosarcoma	protein, Alternative splicing,
  		oncogene homolog	Chromosomal translocation
  		(avian)
  NM_005379	MYO1A	myosin IA	Myosin, Actin-binding, ATP-binding,	2829	6797
  			Calmodulin-binding, Repeat,
  			Multigene family, Polymorphism,
  			Disease mutation, Deafness
  NM_005381	NCL	nucleolin	Hypothetical protein	2830	6798
  NM_005402	RALA	v-ral simian	GTP-binding, Prenylation,	2831	6799
  		leukemia viral	Lipoprotein
  		oncogene homolog
  		A (ras related)
  NM_005428	VAV1	vav 1 oncogene	Hypothetical protein, SH3 domain,	2832	6800
  			Proto-oncogene, Phorbol-ester
  			binding, Zinc, SH2 domain, Guanine-
  			nucleotide releasing factor, Repeat,
  			Phosphorylation
  NM_005433	YES1	v-yes-1 Yamaguchi	Proto-oncogene, Tyrosine-protein	2833	6801
  		sarcoma viral	kinase, Phosphorylation,
  		oncogene homolog 1	Transferase, ATP-binding, Myristate,
  			SH3 domain, SH2 domain,
  			Lipoprotein
  NM_005436	D10S170	DNA segment on	Proto-oncogene, Chromosomal	2834	6802
  		chromosome 10	translocation, SH3-binding, Repeat
  		(unique) 170
  NM_005439	MLF2	myeloid leukemia	Nuclear protein	2835	6803
  		factor 2
  NM_005441	CHAF1B	chromatin assembly	DNA replication, DNA repair, Cell	2836	6804
  		factor 1, subunit B	cycle, Nuclear protein,
  		(p60)	Phosphorylation, Repeat, WD repeat
  NM_005451	ENIGMA	enigma (LIM domain	LIM domain, Metal-binding, Zinc	2837	6805
  		protein)
  NM_005463	HNRPDL	heterogeneous	Nucleocapsid, Ribonucleoprotein	2838	6806
  		nuclear
  		ribonucleoprotein D-
  		like
  NM_005466	MED6	mediator of RNA	Transcription regulation, Activator,	2839	6807
  		polymerase II	Receptor, Nuclear protein
  		transcription,subunit
  		6 homolog (yeast)
  NM_005472	KCNE3	potassium voltage-	Transport, Ion transport, Ionic	2840	6808
  		gated channel, lsk-	channel, Voltage-gated channel,
  		related family,	Potassium channel, Potassium,
  		member 3	Potassium transport,
  			Transmembrane, Glycoprotein,
  			Disease mutation
  NM_005479	FRAT1	frequently	Wnt signaling pathway, Proto-	2841	6809
  		rearranged in	oncogene, 3D-structure
  		advanced T-cell
  		lymphomas
  NM_005480	TROAP	trophinin associated	Cell adhesion, Repeat, Cytoskeleton	2842	6810
  		protein (tastin)
  NM_005488	TOM1	target of myb1	Hypothetical protein, Transport,	2843	6811
  		(chicken)	Protein transport, Membrane, 3D-
  			structure
  NM_005490	SH2D3A	SH2 domain	Hypothetical protein	2844	6812
  		containing 3A
  NM_005498	AP1M2	adaptor-related	Golgi stack, Protein transport,	2845	6813
  		protein complex 1,	Transport, Coated pits, Endocytosis,
  		mu 2 subunit	Phosphorylation, Alternative splicing
  NM_005499	UBA2	SUMO-1 activating	Cyclin, Hypothetical protein	2846	6814
  		enzyme subunit 2
  NM_005501	ITGA3	integrin,alpha 3	Integrin, Cell adhesion, Receptor,	2847	6815
  		(antigen CD49C,	Glycoprotein, Transmembrane,
  		alpha 3 subunit of	Signal, Phosphorylation, Repeat,
  		VLA-3 receptor)	Alternative splicing, Calcium
  NM_005504	BCAT1	branched chain	Transferase, Aminotransferase,	2848	6816
  		aminotransferase 1,	Branched-chain amino acid
  		cytosolic	biosynthesis, Pyridoxal phosphate,
  			Hypothetical protein
  NM_005505	SCARB1	scavenger receptor	Transcription regulation, Nuclear	2849	6817
  		class B,member 1	protein, Receptor, Transmembrane,
  			Glycoprotein, Polymorphism,
  			Alternative splicing
  NM_005507	CFL1	cofilin 1 (non-	Nuclear protein, Actin-binding,	2850	6818
  		muscle)	Cytoskeleton, Phosphorylation
  NM_005510	DOM3Z	dom-3 homolog Z	Transferase, Serine/threonine-	2851	6819
  		(C. elegans)	protein kinase, ATP-binding,
  			Manganese, Nuclear protein,
  			Alternative splicing
  NM_005512	GARP	glycoprotein A	Glycoprotein, Leucine-rich repeat,	2852	6820
  		repetitions	Repeat, Transmembrane, Signal
  		predominant
  NM_005514	HLA-B	major	Glycoprotein, MHC I, Signal,	2853	6821
  		histocompatibility	Transmembrane, Polymorphism, 3D-
  		complex, class I, B	structure, Alternative splicing,
  			Hypothetical protein, Sulfation
  NM_005516	HLA-E	major	Glycoprotein, Transmembrane,	2854	6822
  		histocompatibility	Hypothetical protein, MHC I, Signal,
  		complex, class I, E	Polymorphism, 3D-structure
  NM_005517	HMGN2	high-mobility group	Hypothetical protein, Microtubule,	2855	6823
  		nucleosomal binding	GTP-binding, Multigene family,
  		domain 2	Nuclear protein, DNA-binding,
  			Polymorphism
  NM_005527	HSPA1L	heat shock 70 kDa	ATP-binding, Multigene family,	2856	6824
  		protein 1-like	Polymorphism
  NM_005534	IFNGR2	interferon gamma	Receptor, Transmembrane,	2857	6825
  		receptor 2 (interferon	Glycoprotein, Signal, Repeat
  		gamma transducer
  		1)
  NM_005541	INPP5D	inositol		2858	6826
  		polyphosphate-5-
  		phosphatase,
  		145 kDa
  NM_005548	KARS	lysyl-tRNA	Aminoacyl-tRNA synthetase, Protein	2859	6827
  		synthetase	biosynthesis, Ligase, ATP-binding,
  			Polymorphism
  NM_005564	LCN2	lipocalin	2	Glycoprotein, Lipocalin, Signal, 3D-	2860	6828
  		(oncogene 24p3)	structure, Pyrrolidone carboxylic acid
  NM_005565	LCP2	lymphocyte cytosolic	SH2 domain, Phosphorylation	2861	6829
  		protein 2 (SH2
  		domain containing
  		leukocyte protein of
  		76 kDa)
  NM_005574	LMO2	LIM domain only 2	Proto-oncogene, Repeat, LIM	2862	6830
  		(rhombotin-like 1)	domain, Metal-binding, Zinc, Nuclear
  			protein, Alternative splicing,
  			Chromosomal translocation
  NM_005578	LPP	LIM domain	LIM domain, Metal-binding, Zinc	2863	6831
  		containing preferred
  		translocation partner
  		in lipoma
  NM_005586	MDFI	MyoD family inhibitor	Differentiation	2864	6832
  NM_005590	MRE11A	MRE11 meiotic	DNA repair, Hydrolase, Nuclease,	2865	6833
  		recombination 11	Endonuclease, Exonuclease,
  		homolog A (S. cerevisiae)	Nuclear protein, Manganese,
  			Meiosis, Alternative splicing,
  			Disease mutation, Polymorphism,
  			Hypothetical protein
  NM_005598	NHLH1	nescient helix loop	DNA-binding, Transcription	2866	6834
  		helix 1	regulation, Differentiation
  NM_005601	NKG7	natural killer cell	Transmembrane	2867	6835
  		group 7 sequence
  NM_005605	PPP3CC	protein phosphatase	Hypothetical protein, Hydrolase,	2868	6836
  		3 (formerly 2B),	Iron, Manganese, Calmodulin-
  		catalytic subunit,	binding, Metal-binding, Zinc,
  		gamma isoform	Multigene family
  		(calcineurin A
  		gamma)
  NM_005607	PTK2	PTK2 protein	Hypothetical protein, ATP-binding,	2869	6837
  		tyrosine kinase 2	Transferase, Kinase, Tyrosine-
  			protein kinase, Phosphorylation,
  			Alternative splicing, 3D-structure
  NM_005608	PTPRCAP	protein tyrosine	Transmembrane, Phosphorylation	2870	6838
  		phosphatase,
  		receptor type, C-
  		associated protein
  NM_005611	RBL2	retinoblastoma-like 2	ATP-binding, Kinase,	2871	6839
  		(p130)	Serine/threonine-protein kinase,
  			Transferase, Transcription
  			regulation, DNA-binding, Nuclear
  			protein, Cell cycle, Phosphorylation,
  			Anti-oncogene
  NM_005620	S100A11	S100 calcium	Calcium-binding	2872	6840
  		binding protein A11
  		(calgizzarin)
  NM_005621	S100A12	S100 calcium	Calcium-binding, Zinc, Metal-	2873	6841
  		binding protein A12	binding, Antibiotic, Fungicide, 3D-
  		(calgranulin C)	structure
  NM_005623	CCL8	chemokine (C-C	Cytokine, Chemotaxis, Signal,	2874	6842
  		motif)ligand 8	Heparin-binding, Inflammatory
  			response, Polymorphism,
  			Pyrrolidone carboxylic acid, 3D-
  			structure
  NM_005625	SDCBP	syndecan binding	Cytoskeleton, Membrane,	2875	6843
  		protein (syntenin)	Endoplasmic reticulum, Nuclear
  			protein, Phosphorylation, Repeat,
  			Polymorphism
  NM_005646	TARBP1	TAR (HIV) RNA		2876	6844
  		bindingprotein 1
  NM_005647	TBL1X	transducin (beta)-like	Repeat, WD repeat	2877	6845
  		1X-linked
  NM_005654	NR2F1	nuclear receptor	Receptor, Transcription regulation,	2878	6846
  		subfamily 2, group F,	DNA-binding, Nuclear protein, Zinc-
  		member 1	finger, Activator
  NM_005658	TRAF1	TNF receptor-	Apoptosis, Coiled coil	2879	6847
  		associatedfactor 1
  NM_005687	FRSB	phenylalanyl-tRNA	Aminoacyl-tRNA synthetase, Protein	2880	6848
  		synthetase beta-	biosynthesis, Ligase, ATP-binding
  		subunit
  NM_005690	DNM1L	dynamin 1-like	Hypothetical protein	2881	6849
  NM_005697	SCAMP2	secretory carrier	Transmembrane, Transport, Protein	2882	6850
  		membrane protein 2	transport, Multigene family
  NM_005704	PTPRU	protein tyrosine	Glycoprotein, Hydrolase, Receptor,	2883	6851
  		phosphatase,	Repeat, Signal, Transmembrane,
  		receptor type, U	Immunoglobulin domain
  NM_005710	PQBP1	polyglutamine	Nuclear protein	2884	6852
  		bindingprotein 1
  NM_005713	COL4A3BP	collagen, type IV,	Transferase, Kinase,	2885	6853
  		alpha 3	Serine/threonine-protein kinase,
  		(Goodpasture	Coiled coil, Alternative splicing
  		antigen) binding
  		protein
  NM_005716	RGS19IP1	regulator of G-		2886	6854
  		protein signalling 19
  		interactingprotein 1
  NM_005717	ARPC5	actin related protein	Cytoskeleton	2887	6855
  		2/3 complex,subunit
  		5, 16 kDa
  NM_005720	ARPC1B	actin related protein	Hypothetical protein, Repeat, WD	2888	6856
  		2/3 complex, subunit	repeat, Polymorphism
  		1B, 41 kDa
  NM_005724	TSPAN-3	transmembrane 4	Glycoprotein, Transmembrane	2889	6857
  		superfamily member 8
  NM_005725	TSPAN-2	tetraspan 2	Glycoprotein, Transmembrane	2890	6858
  NM_005730	OS4	CTD (carboxy-	Hypothetical protein, Nuclear protein	2891	6859
  		terminal domain,
  		RNA polymerase II,
  		polypeptide A)small
  		phosphatase
  2
  NM_005731	ARPC2	actin related protein	Cytoskeleton	2892	6860
  		2/3 complex,subunit
  		2, 34 kDa
  NM_005732	RAD50	RAD50 homolog (S. cerevisiae)		2893	6861
  NM_005733	KIF20A	kinesin family	Motor protein, Microtubule, ATP-	2894	6862
  		member 20A	binding, Coiled coil, Golgi stack,
  			Protein transport, Transport
  NM_005736	ACTR1A	ARP1 actin-related	Structural protein, Cytoskeleton,	2895	6863
  		protein 1 homolog A,	Multigene family
  		centractin alpha
  		(yeast)
  NM_005737	ARL7	ADP-ribosylation	GTP-binding, Multigene family,	2896	6864
  		factor-like 7	Nuclear protein
  NM_005741	ZNF263	zinc finger protein	Transcription regulation, Zinc-finger,	2897	6865
  		263	Metal-binding, Nuclear protein, DNA-
  			binding, Repeat, Repressor
  NM_005759	ABI-2	abl-interactor 2	Kinase, SH3 domain	2898	6866
  NM_005761	PLXNC1	plexin C1		2899	6867
  NM_005762	TRIM28	tripartite motif-	Transcription regulation, Repressor,	2900	6868
  		containing 28	Nuclear protein, Zinc-finger, Repeat,
  			3D-structure
  NM_005770	SERF2	small EDRK-rich	Hypothetical protein	2901	6869
  		factor 2
  NM_005771	RDHL	dehydrogenase/reductase	Oxidoreductase	2902	6870
  		(SDR family)
  		member 9
  NM_005772	PLAA	RNA terminal	Repeat, WD repeat, Hypothetical	2903	6871
  		phosphate cyclase-	protein, Nuclear protein
  		like 1
  NM_005773	ZNF256	zinc finger protein	Transcription regulation, DNA-	2904	6872
  		256	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  NM_005787	NOT56L	asparagine-linked	Hypothetical protein, Transferase,	2905	6873
  		glycosylation 3	Glycosyltransferase,
  		homolog (yeast,	Transmembrane, Endoplasmic
  		alpha-1,3-	reticulum, Disease mutation
  		mannosyltransferase)
  NM_005797	EVA1	epithelial V-like	Cell adhesion, Immunoglobulin	2906	6874
  		antigen 1	domain, Transmembrane,
  			Glycoprotein, Signal
  NM_005803	FLOT1	flotillin	1	Membrane	2907	6875
  NM_005805	PSMD14	proteasome	Proteasome	2908	6876
  		(prosome,
  		macropain) 26S
  		subunit, non-
  		ATPase, 14
  NM_005811	GDF11	growth differentiation	Growth factor, Cytokine,	2909	6877
  		factor 11	Glycoprotein, Signal
  NM_005826	HNRPR	heterogeneous	Nucleocapsid, Ribonucleoprotein,	2910	6878
  		nuclear	Nuclear protein, RNA-binding,
  		ribonucleoprotein R	Repeat
  NM_005833	RAB9P40	Rab9 effector p40		2911	6879
  NM_005834	TIMM17B	translocase of inner	Transport, Protein transport,	2912	6880
  		mitochondrial	Translocation, Mitochondrion, Inner
  		membrane 17	membrane, Transmembrane
  		homolog B (yeast)
  NM_005836	UK114	translational inhibitor	Nuclear protein	2913	6881
  		protein p14.5
  NM_005845	ABCC4	ATP-binding	ATP-binding, Glycoprotein,	2914	6882
  		cassette, sub-family	Transmembrane, Transport, Repeat
  		C (CFTR/MRP),
  		member 4
  NM_005849	IGSF6	immunoglobulin	Signal, Hypothetical protein	2915	6883
  		superfamily,member 6
  NM_005855	RAMP1	receptor (calcitonin)	Signal, Transmembrane, Transport,	2916	6884
  		activity modifying	Receptor
  		protein
  1
  NM_005860	FSTL3	follistatin-like 3	Glycoprotein, Repeat, Signal,	2917	6885
  		(secreted	Chromosomal translocation, Proto-
  		glycoprotein)	oncogene
  NM_005862	STAG1	stromal antigen 1	Mitosis, Cell cycle, Chromosome	2918	6886
  			partition, Nuclear protein,
  			Phosphorylation
  NM_005863	NET1	neuroepithelial cell		2919	6887
  		transforminggene 1
  NM_005865	PRSS16	protease, serine, 16	Hydrolase, Serine protease, Signal	2920	6888
  		(thymus)
  NM_005866	SR-BP1	opioid receptor,	Hypothetical protein, Receptor	2921	6889
  		sigma 1
  NM_005873	RGS19	regulator of G-	Signal transduction inhibitor,	2922	6890
  		protein signalling 19	Membrane, Lipoprotein, Palmitate,
  			Phosphorylation, Autophagy, 3D-
  			structure
  NM_005874	LILRB2	leukocyte	Receptor, Repeat, Signal,	2923	6891
  		immunoglobulin-like	Transmembrane, Immune response,
  		receptor, subfamily	Immunoglobulin domain,
  		B (with TM and ITIM	Phosphorylation, Glycoprotein,
  		domains),member 2	Antigen, Multigene family,
  			Alternative splicing, Polymorphism
  NM_005884	PAK4	p21(CDKN1A)-	Hypothetical protein, ATP-binding,	2924	6892
  		activatedkinase 4	Transferase, Serine/threonine-
  			protein kinase, Phosphorylation,
  			Alternative splicing
  NM_005886	KATNB1	katanin p80 (WD	Repeat, WD repeat	2925	6893
  		repeat containing)
  		subunit B 1
  NM_005888	SLC25A3	solute carrier family	Mitochondrion, Inner membrane,	2926	6894
  		25 (mitochondrial	Repeat, Transit peptide,
  		carrier; phosphate	Transmembrane, Transport,
  		carrier),member 3	Symport, Alternative splicing,
  			Hypothetical protein
  NM_005891	ACAT2	acetyl-Coenzyme A	Chaperone, ATP-binding, Multigene	2927	6895
  		acetyltransferase 2	family, Transferase
  		(acetoacetyl
  		Coenzyme A
  		thiolase)
  NM_005892	FMNL	formin-like 1	Hypothetical protein	2928	6896
  NM_005898	M11S1	membrane	GPI-anchor	2929	6897
  		component,
  		chromosome 11,
  		surface marker 1
  NM_005900	MADH1	MAD, mothers	Transcription regulation,	2930	6898
  		against	Phosphorylation, Multigene family,
  		decapentaplegic	3D-structure
  		homolog 1
  		(Drosophila)
  NM_005902	MADH3	MAD, mothers	Transcription regulation,	2931	6899
  		against	Phosphorylation, Multigene family,
  		decapentaplegic	3D-structure
  		homolog 3
  		(Drosophila)
  NM_005917	MDH1	malate	Oxidoreductase, Tricarboxylic acid	2932	6900
  		dehydrogenase 1,	cycle, NAD
  		NAD (soluble)
  NM_005931	MICB	MHC class I	Glycoprotein, Transmembrane, MHC	2933	6901
  		polypeptide-related
  		sequence B
  NM_005932	MIPEP	mitochondrial	Hydrolase, Metalloprotease, Zinc,	2934	6902
  		intermediate	Transit peptide, Mitochondrion,
  		peptidase	Magnesium, Manganese, Calcium,
  			Cobalt, Iron
  NM_005935	MLLT2	myeloid/lymphoid or	Alternative splicing, Chromosomal	2935	6903
  		mixed-lineage	translocation, Proto-oncogene, DNA-
  		leukemia (trithorax	binding, Bromodomain, Nuclear
  		homolog,	protein, Zinc-finger, Metal-binding,
  		Drosophila);	Transcription regulation, Repeat,
  		translocated to, 2	Hypothetical protein,
  			Serine/threonine-protein kinase,
  			Transferase, ATP-binding, Tran
  NM_005950	MT1G	metallothionein 1G	Metal-binding, Metal-thiolate cluster,	2936	6904
  			Zinc, Copper, Cadmium, Acetylation
  NM_005952	MT1X	metallothionein 1X	Hypothetical protein, Metal-binding,	2937	6905
  			Metal-thiolate cluster, Zinc, Copper,
  			Cadmium, Acetylation
  NM_005953	MT2A	metallothionein 2A	Metal-binding, Metal-thiolate cluster,	2938	6906
  			Zinc, Acetylation, 3D-structure
  NM_005954	MT3	metallothionein	3	Metal-binding, Metal-thiolate cluster,	2939	6907
  		(growth inhibitory	Zinc, Copper, Acetylation
  		factor (neurotrophic))
  NM_005955	MTF1	metal-regulatory	Hypothetical protein, Metal-binding,	2940	6908
  		transcription factor 1	Zinc, Zinc-finger
  NM_005965	MYLK	myosin, light	Immunoglobulin domain, Kinase,	2941	6909
  		polypeptide kinase	ATP-binding, Repeat,
  			Serine/threonine-protein kinase,
  			Transferase, Calmodulin-binding,
  			Phosphorylation, Alternative
  			initiation, Alternative splicing
  NM_005969	NAP1L4	nucleosome	Nuclear protein	2942	6910
  		assembly protein 1-
  		like 4
  NM_005975	PTK6	PTK6 protein	Transferase, Tyrosine-protein	2943	6911
  		tyrosine kinase 6	kinase, ATP-binding, SH2 domain,
  			SH3 domain, Phosphorylation
  NM_005979	S100A13	S100 calcium	Calcium-binding	2944	6912
  		binding protein A13
  NM_005980	S100P	S100 calcium	Calcium-binding, Placenta, 3D-	2945	6913
  		binding protein P	structure
  NM_005988	SPRR2A	small proline-rich	Keratinocyte, Repeat, Multigene	2946	6914
  		protein 2A	family
  NM_005990	STK10	serine/threonine	Kinase, Transferase,	2947	6915
  		kinase 10	Serine/threonine-protein kinase,
  			ATP-binding, Phosphorylation,
  			Coiled coil
  NM_005998	CCT3	chaperonin	Chaperone, ATP-binding, Multigene	2948	6916
  		containing TCP1,	family, Hypothetical protein
  		subunit 3 (gamma)
  NM_006002	UCHL3	ubiquitin carboxyl-	Ubl conjugation pathway, Hydrolase,	2949	6917
  		terminal esterase L3	Thiol protease, Multigene family, 3D-
  		(ubiquitin	structure
  		thiolesterase)
  NM_006018	HM74	putative chemokine	G-protein coupled receptor,	2950	6918
  		receptor	Transmembrane
  NM_006019	TCIRG1	T-cell, immune	Hydrogen ion transport,	2951	6919
  		regulator 1, ATPase,	Transmembrane, Glycoprotein,
  		H+ transporting,	Alternative splicing, Hypothetical
  		lysosomal V0 protein	protein
  		aisoform 3
  NM_006022	TSC22	transforming growth	Hypothetical protein, Transcription	2952	6920
  		factor beta-	regulation, Repressor, Nuclear
  		stimulated protein	protein
  		TSC-22
  NM_006027	EXO1	exonuclease 1	Exonuclease, Hypothetical protein	2953	6921
  NM_006029	PNMA1	paraneoplastic	Antigen, Tumor antigen, Nuclear	2954	6922
  		antigen MA1	protein
  NM_006031	PCNT2	pericentrin 2	Coiled coil, Hypothetical protein	2955	6923
  		(kendrin)
  NM_006034	TP53I11	tumor protein p53	Hypothetical protein	2956	6924
  		inducible protein 11
  NM_006053	TCIRG1	T-cell, immune	Hydrogen ion transport,	2957	6925
  		regulator 1, ATPase,	Transmembrane, Glycoprotein,
  		H+ transporting,	Alternative splicing, Hypothetical
  		lysosomal V0 protein	protein
  		aisoform 3
  NM_006054	RTN3	reticulon	3	Hypothetical protein,	2958	6926
  			Transmembrane, Endoplasmic
  			reticulum
  NM_006055	LANCL1	LanC lantibiotic	Transmembrane	2959	6927
  		synthetase
  		component C-like 1
  		(bacterial)
  NM_006060	ZNFN1A1	zinc finger protein,	Transcription regulation, Activator,	2960	6928
  		subfamily 1A, 1	Zinc-finger, Metal-binding, DNA-
  		(lkaros)	binding, Nuclear protein, Repeat,
  			Alternative splicing
  NM_006061	SGP28	cysteine-rich	Glycoprotein, Signal, Multigene	2961	6929
  		secretory protein 3	family, Polymorphism
  NM_006069	MRVI1	murine retrovirus		2962	6930
  		integration site 1
  		homolog
  NM_006070	TFG	TRK-fused gene	Hypothetical protein, Ligase, GMP	2963	6931
  			biosynthesis, Purine biosynthesis,
  			ATP-binding, Glutamine
  			amidotransferase
  NM_006079	CITED2	Cbp/p300-interacting	Transcription regulation, Nuclear	2964	6932
  		transactivator, with	protein, Alternative splicing
  		Glu/Asp-rich
  		carboxy-terminal
  		domain, 2
  NM_006088	TUBB2	tubulin, beta, 2	Microtubule, GTP-binding, Multigene	2965	6933
  			family, Hypothetical protein
  NM_006093	PRG3	proteoglycan	3		2966	6934
  NM_006097	MYL9	myosin, light	Myosin, Calcium-binding, Muscle	2967	6935
  		polypeptide 9,	protein, Phosphorylation,
  		regulatory	Acetylation, Multigene family
  NM_006103	WFDC2	WAP four-disulfide	Serine protease inhibitor, Repeat,	2968	6936
  		core domain 2	Signal, Glycoprotein, Alternative
  			splicing
  NM_006107	LUC7A	acid-inducible	Phosphorylation, Hypothetical	2969	6937
  		phosphoprotein	protein
  NM_006109	SKB1	SKB1 homolog (S. pombe)	Transferase, Methyltransferase,	2970	6938
  			Alternative splicing
  NM_006111	ACAA2	acetyl-Coenzyme A	Acyltransferase, Transferase, Fatty	2971	6939
  		acyltransferase 2	acid metabolism, Mitochondrion,
  		(mitochondrial 3-	Transit peptide
  		oxoacyl-Coenzyme
  		A thiolase)
  NM_006113	VAV3	vav	3 oncogene	SH3 domain, Phorbol-ester binding,	2972	6940
  			Zinc, SH2 domain, Repeat, Guanine-
  			nucleotide releasing factor,
  			Alternative splicing
  NM_006115	PRAME	preferentially	Antigen	2973	6941
  		expressed antigen in
  		melanoma
  NM_006117	PECI	peroxisomal D3,D2-	Isomerase, Hypothetical protein,	2974	6942
  		enoyl-CoA	Peroxisome
  		isomerase
  NM_006135	CAPZA1	capping protein	Actin-binding, Multigene family, 3D-	2975	6943
  		(actin filament)	structure, Actin capping
  		muscle Z-line,alpha 1
  NM_006138	MS4A3	membrane-spanning	Receptor, Transmembrane,	2976	6944
  		4-domains,	Alternative splicing, Multigene family
  		subfamily A,
  		member 3
  		(hematopoietic cell-
  		specific)
  NM_006139	CD28	CD28 antigen (Tp44)	Immunoglobulin domain, T-cell,	2977	6945
  			Glycoprotein, Signal,
  			Transmembrane, Alternative splicing
  NM_006140	CSF2RA	colony stimulating	Receptor, Transmembrane,	2978	6946
  		factor 2 receptor,	Glycoprotein, Signal, Alternative
  		alpha, low-affinity	splicing
  		(granulocyte-
  		macrophage)
  NM_006142	SFN	stratifin	Multigene family	2979	6947
  NM_006144	GZMA	granzyme A	Hydrolase, Serine protease,	2980	6948
  		(granzyme 1,	Zymogen, Signal, T-cell, Cytolysis,
  		cytotoxic T-	Apoptosis, 3D-structure
  		lymphocyte-
  		associated serine
  		esterase 3)
  NM_006145	DNAJB1	DnaJ (Hsp40)	Heat shock, Chaperone, 3D-	2981	6949
  		homolog, subfamily	structure
  		B,member 1
  NM_006147	IRF6	interferon regulatory	Transcription regulation, DNA-	2982	6950
  		factor 6	binding, Nuclear protein,
  			Polymorphism, Disease mutation
  NM_006148	LASP1	LIM andSH3 protein 1	LIM domain, Metal-binding, Zinc,	2983	6951
  			SH3 domain
  NM_006159	NELL2	NEL-like 2 (chicken)	EGF-like domain, Glycoprotein,	2984	6952
  			Repeat, Signal
  NM_006161	NEUROG1	neurogenin 1	DNA-binding, Nuclear protein,	2985	6953
  			Transcription regulation, Activator,
  			Neurogenesis, Developmental
  			protein, Differentiation
  NM_006176	NRGN	neurogranin (protein	Calmodulin-binding,	2986	6954
  		kinase C substrate,	Phosphorylation, Neurone
  		RC3)
  NM_006185	NUMA1	nuclear mitotic	Immunoglobulin domain,	2987	6955
  		apparatus protein 1	Glycoprotein, Signal, Alternative
  			splicing, Hypothetical protein
  NM_006196	PCBP1	poly(rC) binding	Nuclear protein, RNA-binding,	2988	6956
  		protein 1	Ribonucleoprotein, DNA-binding,
  			Phosphorylation, Repeat
  NM_006202	PDE4A	phosphodiesterase	Hydrolase, cAMP, Alternative	2989	6957
  		4A, cAMP-specific	splicing, Multigene family
  		(phosphodiesterase
  		E2 dunce homolog,
  		Drosophila)
  NM_006205	PDE6H	phosphodiesterase	Hydrolase, cGMP, Vision	2990	6958
  		6H, cGMP-specific,
  		cone, gamma
  NM_006214	PHYH	phytanoyl-CoA	Oxidoreductase, Peroxisome,	2991	6959
  		hydroxylase	Vitamin C, Iron, Transit peptide,
  		(Refsum disease)	Disease mutation, Deafness,
  			Retinitis pigmentosa, Hydrolase,
  			cGMP, Vision, Prenylation,
  			Lipoprotein, Membrane, Hypothetical
  			protein, Collagen
  NM_006224	PITPN	phosphotidylinositol	Lipid-binding, Transport	2992	6960
  		transfer protein
  NM_006225	PLCD1	phospholipase C,	Hydrolase, Lipid degradation,	2993	6961
  		delta 1	Transducer, Calcium-binding,
  			Repeat
  NM_006238	PPARD	peroxisome	Receptor, Transcription regulation,	2994	6962
  		proliferative	Activator, DNA-binding, Nuclear
  		activated receptor,	protein, Zinc-finger, Multigene family,
  		delta	3D-structure, Metal-binding
  NM_006242	PPP1R3D	protein phosphatase	Hydrolase, Glycogen metabolism	2995	6963
  		1, regulatory subunit
  		3D
  NM_006243	PPP2R5A	protein phosphatase	Phosphorylation, Multigene family	2996	6964
  		2, regulatory subunit
  		B (B56), alpha
  		isoform
  NM_006244	PPP2R5B	protein phosphatase	Phosphorylation, Alternative splicing,	2997	6965
  		2, regulatory subunit	Multigene family
  		B (B56), beta
  		isoform
  NM_006254	PRKCD	protein kinase C,	ATP-binding, Transferase,	2998	6966
  		delta	Serine/threonine-protein kinase,
  			Phorbol-ester binding, Zinc, Repeat,
  			Polymorphism, Phosphorylation,
  			Membrane
  NM_006272	S100B	S100 calcium	Calcium-binding, Zinc, Metal-	2999	6967
  		binding protein, beta	binding, 3D-structure
  		(neural)
  NM_006284	TAF10	TAF10 RNA	Transcription regulation, Nuclear	3000	6968
  		polymerase II, TATA	protein, Polymorphism
  		box binding protein
  		(TBP)-associated
  		factor, 30 kDa
  NM_006287	TFPI	tissue factor	Serine protease inhibitor,	3001	6969
  		pathway inhibitor	Glycoprotein, Repeat, Blood
  		(lipoprotein-	coagulation, Signal, Alternative
  		associated	splicing, 3D-structure, Polymorphism
  		coagulation inhibitor)
  NM_006289	TLN1	talin	1	Hypothetical protein, Structural	3002	6970
  			protein, Cytoskeleton
  NM_006290	TNFAIP3	tumor necrosis	Apoptosis, DNA-binding, Zinc-finger,	3003	6971
  		factor, alpha-induced	Repeat,Hypothetical protein
  		protein
  3
  NM_006291	TNFAIP2	tumor necrosis	Angiogenesis	3004	6972
  		factor, alpha-induced
  		protein 2
  NM_006304	DSS1	split hand/foot	Polymorphism, 3D-structure	3005	6973
  		malformation
  		(ectrodactyly)type 1
  NM_006310	NPEPPS	aminopeptidase	Hydrolase, Metalloprotease,	3006	6974
  		puromycin sensitive	Aminopeptidase, Zinc, Nuclear
  			protein
  NM_006314	CNK1	connector enhancer	Hypothetical protein, Kinase	3007	6975
  		of KSR-like
  		(Drosophilakinase
  		suppressor of ras)
  NM_006317	BASP1	brain abundant,	Membrane, Myristate, Neurone,	3008	6976
  		membrane attached	Lipoprotein
  		signal protein
  1
  NM_006319	CDIPT	CDP-diacylglycerol--	Transferase, Phospholipid	3009	6977
  		inositol 3-	biosynthesis, Transmembrane,
  		phosphatidyltransferase	Magnesium, Manganese
  		(phosphatidylinositol
  		synthase)
  NM_006321	ARIH2	ariadne homolog	2	Ubl conjugation pathway, Nuclear	3010	6978
  		(Drosophila)	protein, Coiled coil, Zinc-finger,
  			Repeat
  NM_006323	SEC24B	SEC24 related gene	Transport, Protein transport, Golgi	3011	6979
  		family, member B (S. cerevisiae)	stack, Endoplasmic reticulum,
  			Multigene family
  NM_006324	CFDP1	craniofacial		3012	6980
  		development protein 1
  NM_006327	TIMM23	translocase of inner	Transport, Protein transport,	3013	6981
  		mitochondrial	Translocation, Mitochondrion,Inner
  		membrane
  23	membrane, Outer membrane,
  		homolog (yeast)	Transmembrane
  NM_006342	TACC3	transforming, acidic	Coiled coil	3014	6982
  		coiled-coil containing
  		protein
  3
  NM_006344	HML2	C-type (calcium	Lectin	3015	6983
  		dependent,
  		carbohydrate-
  		recognition domain)
  		lectin, superfamily
  		member 13
  		(macrophage-
  		derived)
  NM_006345	C4orf1	solute carrier family	Hypothetical protein	3016	6984
  		30 (zinc transporter),
  		member 9
  NM_006346	PIBF1	progesterone-		3017	6985
  		inducedblocking
  		factor
  1
  NM_006351	TIMM44	translocase of inner	Mitochondrion, Inner membrane,	3018	6986
  		mitochondrial	Transport, Protein transport,
  		membrane 44	Translocation, Transit peptide, ATP-
  		homolog (yeast)	binding, Receptor
  NM_006353	HMGN4	high mobility group	Nuclear protein, DNA-binding	3019	6987
  		nucleosomalbinding
  		domain
  4
  NM_006355	TRIM38	tripartite motif-	Zinc-finger, Polymorphism	3020	6988
  		containing 38
  NM_006360	GA17	dendritic cell protein	Hypothetical protein	3021	6989
  NM_006362	NXF1	nuclear RNA export	Transport, mRNA transport, Nuclear	3022	6990
  		factor 1	protein, RNA-binding, Repeat,
  			Leucine-rich repeat, Multigene
  			family, 3D-structure
  NM_006367	CAP	CAP, adenylate	Membrane, Multigene family	3023	6991
  		cyclase-associated
  		protein 1 (yeast)
  NM_006374	STK25	serine/threonine	Hypothetical protein, ATP-binding,	3024	6992
  		kinase 25 (STE20	Transferase, Serine/threonine-
  		homolog, yeast)	protein kinase, Phosphorylation
  NM_006377	UNC13	unc-13 homolog B	Phorbol-ester binding	3025	6993
  		(C. elegans)
  NM_006383	KIP2	DNA-dependent	Calcium-binding, Repeat	3026	6994
  		protein kinase
  		catalytic subunit-
  		interactingprotein 2
  NM_006386	DDX17	DEAD (Asp-Glu-Ala-	ATP-binding, RNA-binding, Helicase,	3027	6995
  		Asp) box polypeptide	Nuclear protein
  		17
  NM_006387	CHERP	calcium homeostasis		3028	6996
  		endoplasmic
  		reticulum protein
  NM_006389	HYOU1	hypoxia up-regulated 1	ATP-binding, Chaperone,	3029	6997
  			Endoplasmic reticulum, Signal,
  			Glycoprotein
  NM_006395	GSA7	APG7 autophagy 7-	Hypothetical protein	3030	6998
  		like (S. cerevisiae)
  NM_006399	BATF	basic leucine zipper	Transcription regulation, DNA-	3031	6999
  		transcription factor,	binding, Repressor, Phosphorylation,
  		ATF-like	Nuclear protein
  NM_006403	NEDD9	neural precursor cell	Phosphorylation, SH3 domain, Cell	3032	7000
  		expressed,	adhesion, Growth regulation,
  		developmentally	Cytoskeleton, Mitosis, Nuclear
  		down-regulated 9	protein
  NM_006404	PROCR	protein C receptor,	Blood coagulation, Receptor, Signal,	3033	7001
  		endothelial (EPCR)	Transmembrane, Glycoprotein,
  			Antigen, Polymorphism, 3D-structure
  NM_006405	TM9SF1	transmembrane 9	Hypothetical protein, Plasmid,	3034	7002
  		superfamily member 1	Signal, Transmembrane,
  			Glycoprotein
  NM_006406	PRDX4	peroxiredoxin 4	Antioxidant, Peroxidase,	3035	7003
  			Oxidoreductase, Redox-active
  			center
  NM_006421	BIG1	brefeldin A-inhibited	Guanine-nucleotide releasing factor	3036	7004
  		guanine nucleotide-
  		exchange protein 1
  NM_006429	CCT7	chaperonin	Chaperone, ATP-binding, Multigene	3037	7005
  		containing TCP1,	family
  		subunit 7 (eta)
  NM_006430	CCT4	chaperonin	Chaperone, ATP-binding, Multigene	3038	7006
  		containing TCP1,	family, Hypothetical protein
  		subunit 4 (delta)
  NM_006431	CCT2	chaperonin	ATP-binding, Chaperone, Multigene	3039	7007
  		containing TCP1,	family
  		subunit 2 (beta)
  NM_006433	GNLY	granulysin	Antibiotic, Fungicide, Signal, T-cell,	3040	7008
  			Alternative splicing, 3D-structure
  NM_006435	IFITM2	interferon induced	Interferon induction,	3041	7009
  		transmembrane	Transmembrane, Polymorphism
  		protein 2 (1-8D)
  NM_006441	MTHFS	5,10-	Ligase, Folate-binding, Acetylation,	3042	7010
  		methenyltetrahydrofolate	Magnesium, Hypothetical protein
  		synthetase (5-
  		formyltetrahydrofolate
  		cyclo-ligase)
  NM_006451	PAIP1	poly(A) binding	Hypothetical protein	3043	7011
  		protein interacting
  		protein
  1
  NM_006452	PAICS	phosphoribosylaminoimidazole	Multifunctional enzyme, Purine	3044	7012
  		carboxylase,	biosynthesis, Ligase, Lyase,
  		phosphoribosylaminoimidazole	Decarboxylase
  		succinocarboxamide
  		synthetase
  NM_006455	SC65	synaptonemal	Nuclear protein, Antigen	3045	7013
  		complex protein
  		SC65
  NM_006456	STHM	sialyltransferase	Transferase, Glycosyltransferase,	3046	7014
  			Glycoprotein, Transmembrane,
  			Signal-anchor, Golgi stack
  NM_006461	SPAG5	sperm associated	Hypothetical protein	3047	7015
  		antigen 5
  NM_006465	DRIL2	dead ringer		3048	7016
  		(Drosophila)-like 2
  		(bright and dead
  		ringer)
  NM_006469	IVNS1ABP	influenza virus NS1A	Hypothetical protein	3049	7017
  		binding protein
  NM_006471	MLC-B	myosin regulatory	Myosin, Calcium-binding, Muscle	3050	7018
  		light chain MRCL3	protein, Phosphorylation,
  			Acetylation, Multigene family
  NM_006472	TXNIP	thioredoxin		3051	7019
  		interacting protein
  NM_006477	RRP22	RAS-related on	GTP-binding, Prenylation,	3052	7020
  		chromosome 22	Lipoprotein
  NM_006480	RGS14	regulator of G-	Repeat, Thiol protease inhibitor,	3053	7021
  		protein signalling 14	Alternative splicing, Phosphorylation,
  			Signal transduction inhibitor
  NM_006495	EVI2B	ecotropic viral	Proto-oncogene, Transmembrane,	3054	7022
  		integration site 2B	Glycoprotein, Signal
  NM_006542	SPHAR	S-phase response		3055	7023
  		(cyclin-related)
  NM_006545	NPR2L	homologous to yeast	Hypothetical protein	3056	7024
  		nitrogen permease
  		(candidate tumor
  		suppressor)
  NM_006560	CUGBP1	CUG triplet repeat,	Hypothetical protein, mRNA	3057	7025
  		RNA binding protein 1	processing, RNA-binding, Repeat,
  			Nuclear protein, Alternative splicing
  NM_006567	FARS1	phenylalanine-tRNA	Aminoacyl-tRNA synthetase	3058	7026
  		synthetase 1
  		(mitochondrial)
  NM_006568	CGR19	cell growth regulator	Metal-binding, Zinc, Zinc-finger	3059	7027
  		withring finger
  		domain
  1
  NM_006575	MAP4K5	mitogen-activated	ATP-binding, Kinase, Transferase,	3060	7028
  		protein kinase	Tyrosine-protein kinase,
  		kinase kinase kinase 5	Serine/threonine-protein kinase
  NM_006578	GNB5	guanine nucleotide	Repeat, WD repeat, Transducer,	3061	7029
  		binding protein (G	Alternative splicing, Multigene family,
  		protein),beta 5	Hypothetical protein
  NM_006589	C1orf2	chromosome	1 open	Hypothetical protein	3062	7030
  		reading frame 2
  NM_006598	SLC12A7	solute carrier family	Transport, Ion transport, Symport,	3063	7031
  		12	Potassium, Potassium transport,
  		(potassium/chloride	Transmembrane, Alternative splicing
  		transporters),
  		member 7
  NM_006636	MTHFD2	methylene	Multifunctional enzyme, One-carbon	3064	7032
  		tetrahydrofolate	metabolism, Oxidoreductase, NAD,
  		dehydrogenase	Hydrolase, Mitochondrion, Transit
  		(NAD+ dependent),	peptide, Magnesium
  		methenyltetrahydrofolate
  		cyclohydrolase
  NM_006638	RNASEP1	ribonuclease P1	Hydrolase, Nuclear protein, tRNA	3065	7033
  			processing
  NM_006643	SDCCAG3	serologically defined	Hypothetical protein	3066	7034
  		colon cancer antigen 3
  NM_006644	HSPH1	heat shock	ATP-binding, Heat shock, Multigene	3067	7035
  		105 kDa/110 kDa	family,Alternative splicing
  		protein
  1
  NM_006646	WASF3	WAS protein family,	Actin-binding, Coiled coil	3068	7036
  		member 3
  NM_006650	CPLX2	complexin	2	Neurotransmitter transport	3069	7037
  NM_006660	CLPX	ClpX caseinolytic	Hypothetical protein, ATP-binding,	3070	7038
  		protease X homolog	Chaperone, Mitochondrion, Transit
  		(E. coli)	peptide, Zinc-finger
  NM_006667	PGRMC1	progesterone	Receptor, Steroid-binding,	3071	7039
  		receptor membrane	Transmembrane,Microsome
  		component
  1
  NM_006669	LILRB1	leukocyte	Receptor, Repeat, Signal,	3072	7040
  		immunoglobulin-like	Transmembrane, Immune response,
  		receptor, subfamily	Immunoglobulin domain,
  		B (with TM and ITIM	Phosphorylation, Glycoprotein,
  		domains),member 1	Antigen, Multigene family,
  			Alternative splicing, Polymorphism,
  			3D-structure
  NM_006676	USP20	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	3073	7041
  		protease 20	Thiol protease, Multigene family
  NM_006680	ME3	malic enzyme 3,	Oxidoreductase, NADP,	3074	7042
  		NADP(+)-	Mitochondrion, Transit peptide
  		dependent,
  		mitochondrial
  NM_006681	NMU	neuromedin U	Neuropeptide, Cleavage on pair of	3075	7043
  			basic residues, Amidation, Signal
  NM_006682	FGL2	fibrinogen-like 2	T-cell, Glycoprotein, Signal,	3076	7044
  			Polymorphism
  NM_006700	FLN29	FLN29 gene product		3077	7045
  NM_006704	SUGT1	SGT1, suppressor of	Ubl conjugation pathway, Repeat,	3078	7046
  		G2 allele of SKP1	TPR repeat
  		(S. cerevisiae)
  NM_006705	GADD45G	growth arrest and	Differentiation, Apoptosis	3079	7047
  		DNA-damage-
  		inducible, gamma
  NM_006706	TCERG1	transcription		3080	7048
  		elongation regulator
  		1 (CA150)
  NM_006708	GLO1	glyoxalase I	Lyase, Zinc, Polymorphism, 3D-	3081	7049
  			structure
  NM_006710	COP9	COP9 signalosome		3082	7050
  		subunit 8
  NM_006719	ABLIM1	actin binding LIM	LIM domain, Metal-binding, Zinc,	3083	7051
  		protein 1	Hypothetical protein
  NM_006721	ADK	adenosine kinase	Transferase, Kinase, Purine salvage,	3084	7052
  			Magnesium, Alternative splicing, 3D-
  			structure
  NM_006732	FOSB	FBJ murine	Nuclear protein, DNA-binding	3085	7053
  		osteosarcoma viral
  		oncogene homolog B
  NM_006747	SIPA1	signal-induced	GTPase activation, Coiled coil,	3086	7054
  		proliferation-	Nuclear protein, Membrane
  		associatedgene 1
  NM_006748	SLA	Src-like-adaptor	SH2 domain, SH3 domain,	3087	7055
  			Myristate, Phosphorylation,
  			Lipoprotein
  NM_006750	SNTB2	syntrophin,beta 2	Actin-binding, Cytoskeleton,	3088	7056
  		(dystrophin-	Microtubule, Calcium-binding,
  		associated protein	Calmodulin-binding, Membrane,
  		A1, 59 kDa, basic	Phosphorylation, Repeat,
  		component 2)	Polymorphism, Multigene family,
  			Alternative splicing
  NM_006755	TALDO1	transaldolase	1	Hypothetical protein, Pentose shunt,	3089	7057
  			Transferase, Disease mutation, 3D-
  			structure
  NM_006756	TCEA1	transcription	Transcription regulation, Zinc-finger,	3090	7058
  		elongation factor A	DNA-binding, Nuclear protein,
  		(SII), 1	Alternative splicing, 3D-structure
  NM_006760	UPK2	uroplakin 2	Endoplasmic reticulum, Signal,	3091	7059
  			Transmembrane, Glycoprotein
  NM_006761	YWHAE	tyrosine 3-	Neurone, Acetylation, Multigene	3092	7060
  		monooxygenase/tryptophan	family
  		5-
  		monooxygenase
  		activation protein,
  		epsilon polypeptide
  NM_006762	LAPTM5	Lysosomal-	Transmembrane, Lysosome	3093	7061
  		associated
  		multispanning
  		membrane protein-5
  NM_006763	BTG2	BTG family,member 2	Signal	3094	7062
  NM_006770	MARCO	macrophage	Collagen, Transmembrane,	3095	7063
  		receptor with	Receptor, Glycoprotein, Signal-
  		collagenous	anchor
  		structure
  NM_006783	GJB6	gap junction protein,	Gap junction, Transmembrane,	3096	7064
  		beta 6 (connexin 30)	Deafness, Disease mutation
  NM_006784	WDR3	WD repeat domain 3	WD repeat, Repeat, Nuclear protein	3097	7065
  NM_006787	MAGED2	melanoma antigen,	Antigen, Multigene family,	3098	7066
  		family D, 2	Polymorphism, Alternative splicing
  NM_006795	EHD1	EH-domain	Calcium-binding, ATP-binding,	3099	7067
  		containing 1	Coiled coil
  NM_006801	KDELR1	KDEL (Lys-Asp-Glu-	Endoplasmic reticulum,	3100	7068
  		Leu) endoplasmic	Transmembrane, Protein transport,
  		reticulum protein	Receptor, Hypothetical protein,
  		retention receptor 1	Transport
  NM_006805	HNRPA0	heterogeneous	Nuclear protein, RNA-binding,	3101	7069
  		nuclear	Ribonucleoprotein, Repeat,
  		ribonucleoprotein A0	Methylation
  NM_006806	BTG3	BTG family,member 3	Alternative splicing	3102	7070
  NM_006810	PDIR	for protein disulfide	Isomerase, Redox-active center,	3103	7071
  		isomerase-related	Endoplasmic reticulum, Repeat,
  			Signal
  NM_006812	OS-9	amplified in	Hypothetical protein, Signal,	3104	7072
  		osteosarcoma	Alternative splicing, Polymorphism
  NM_006818	AF1Q	ALL1-fused gene	Proto-oncogene, Chromosomal	3105	7073
  		from chromosome	translocation
  		1q
  NM_006823	PKIA	protein kinase	Protein kinase inhibitor, 3D-structure	3106	7074
  		(cAMP-dependent,
  		catalytic) inhibitor
  		alpha
  NM_006824	EBNA1BP2	EBNA1 binding	Ribosome biogenesis, Nuclear	3107	7075
  		protein 2	protein, Coiled coil
  NM_006825	CKAP4	cytoskeleton-	Hypothetical protein	3108	7076
  		associatedprotein 4
  NM_006826	YWHAQ	tyrosine 3-	Transcription regulation, Repressor,	3109	7077
  		monooxygenase/tryptophan	Activator, Nuclear protein, Zinc-
  		5-	finger, Metal-binding, DNA-binding,
  		monooxygenase	Repeat, 3D-structure, Tight junction,
  		activation protein,	Immunoglobulin domain,
  		theta polypeptide	Glycoprotein, Transmembrane,
  			Signal, Neurone, Phosphorylation,
  			Multigene family
  NM_006827	TMP21	transmembrane	Transport, Protein transport,	3110	7078
  		trafficking protein	Transmembrane, Signal,
  			Glycoprotein, Golgi stack,
  			Polymorphism
  NM_006838	METAP2	methionyl	Hydrolase, Aminopeptidase, Cobalt,	3111	7079
  		aminopeptidase 2	3D-structure, Hypothetical protein
  NM_006840	LILRB5	leukocyte	Receptor, Repeat, Signal,	3112	7080
  		immunoglobulin-like	Transmembrane, Immune response,
  		receptor, subfamily	Immunoglobulin domain,
  		B (with TM and ITIM	Phosphorylation, Glycoprotein,
  		domains),member 2	Antigen, Multigene family,
  			Alternative splicing
  NM_006863	LILRA1	leukocyte	Immune response, Receptor,	3113	7081
  		immunoglobulin-like	Repeat, Signal, Transmembrane,
  		receptor, subfamily	Immunoglobulin domain,
  		B (with TM and ITIM	Glycoprotein, Antigen, Alternative
  		domains),member 1	splicing, Multigene family
  NM_006864	LILRB3	leukocyte	Receptor, Repeat, Signal,	3114	7082
  		immunoglobulin-like	Transmembrane, Immune response,
  		receptor, subfamily	Immunoglobulin domain,
  		B (with TM and ITIM	Phosphorylation, Glycoprotein,
  		domains),member 3	Antigen, Multigene family,
  			Alternative splicing, Polymorphism
  NM_006865	LILRA3	leukocyte	Receptor, Repeat, Signal, Immune	3115	7083
  		immunoglobulin-like	response, Immunoglobulin domain,
  		receptor, subfamily	Glycoprotein, Antigen, Multigene
  		A (without TM	family, Polymorphism
  		domain),member 3
  NM_006866	LILRA2	leukocyte	Immune response, Receptor,	3116	7084
  		immunoglobulin-like	Repeat, Signal, Transmembrane,
  		receptor, subfamily	Immunoglobulin domain,
  		B (with TM and ITIM	Glycoprotein, Antigen, Alternative
  		domains),member 1	splicing, Polymorphism, Multigene
  			family
  NM_006868	RAB31	RAB31, member	GTP-binding, Lipoprotein,	3117	7085
  		RAS oncogene	Prenylation
  		family
  NM_006869	CENTA1	centaurin,alpha 1		3118	7086
  NM_006876	B3GNT6	UDP-	Transferase, Glycosyltransferase,	3119	7087
  		GlcNAc:betaGal	Transmembrane, Signal-anchor,
  		beta-1,3-N-	Glycoprotein, Golgistack
  		acetylglucosaminyltransferase
  6
  NM_006890	CEACAM7	carcinoembryonic	Immunoglobulin domain, Antigen,	3120	7088
  		antigen-related cell	Membrane, Signal, Glycoprotein,
  		adhesion molecule 7	Lipoprotein, GPI-anchor, Repeat,
  			Alternative splicing
  NM_006892	DNMT3B	DNA (cytosine-5-)-	Transferase, Methyltransferase,	3121	7089
  		methyltransferase 3	Zinc-finger, Zinc, Metal-binding,
  		beta	Nuclear protein, Ubl conjugation,
  			Alternative splicing, Disease
  			mutation
  NM_006913	RNF5	ring finger protein 5	Hypothetical protein	3122	7090
  NM_006923	SDF2	stromal cell-derived	Signal, Repeat	3123	7091
  		factor 2
  NM_006930	SKP1A	S-phase kinase-	Ubl conjugation pathway, Alternative	3124	7092
  		associated protein	splicing, 3D-structure
  		1A (p19A)
  NM_006931	SLC2A3	solute carrier family	Sugar transport, Transmembrane,	3125	7093
  		2 (facilitated glucose	Transport, Glycoprotein, Multigene
  		transporter),	family
  		member
  3
  NM_006932	SMTN	smoothelin	Structural protein, Alternative	3126	7094
  			splicing
  NM_006936	SMT3H1	SMT3 suppressor of	Ubl conjugation pathway	3127	7095
  		mif two 3 homolog 1
  		(yeast)
  NM_006938	SNRPD1	small nuclear	Nuclear protein, Ribonucleoprotein,	3128	7096
  		ribonucleoprotein D1	mRNA splicing, mRNA processing,
  		polypeptide 16 kDa	Systemic lupus erythematosus,
  			Repeat, Methylation, 3D-structure
  NM_006941	SOX10	SRY (sex	Transcription regulation, DNA-	3129	7097
  		determining region	binding, Nuclear protein, Disease
  		Y)-box 10	mutation, Hirschsprung disease,
  			Deafness
  NM_006945	SPRR2B	small proline-rich	Keratinocyte, Repeat, Multigene	3130	7098
  		protein 2B	family
  NM_006947	SRP72	signal recognition	ATP-binding, Kinase, Transferase,	3131	7099
  		particle 72 kDa	Signal recognition particle,
  			Ribonucleoprotein
  NM_006987	RPH3AL	rabphilin 3A-like	Hypothetical protein	3132	7100
  		(without C2
  		domains)
  NM_006993	NPM3	nucleophosmin/nucleoplasmin, 3	Nuclear protein, Chaperone,	3133	7101
  			Phosphorylation
  NM_007000	UPK1A	uroplakin 1A	Hypothetical protein,	3134	7102
  			Transmembrane, Glycoprotein
  NM_007007	CPSF6	cleavage and		3135	7103
  		polyadenylation
  		specific factor 6,
  		68 kDa
  NM_007008	RTN4	reticulon	4	Endoplasmic reticulum, Alternative	3136	7104
  			splicing, Transmembrane,
  			Hypothetical protein
  NM_007014	WWP2	Nedd-4-like	Ubl conjugation pathway, Ligase,	3137	7105
  		ubiquitin-protein	Repeat
  		ligase
  NM_007022	101F6	putative tumor		3138	7106
  		suppressor 101F6
  NM_007024	PL6	placental protein 6	Transmembrane	3139	7107
  NM_007032	HRIHFB2122	Tara-like protein	Hypothetical protein, Cytoskeleton,	3140	7108
  			Actin-binding, Coiled coil, Nuclear
  			protein
  NM_007033	RER1	RER1 homolog (S. cerevisiae)	Transmembrane, Golgi stack	3141	7109
  NM_007034	DNAJB4	DnaJ (Hsp40)	Chaperone, Heat shock	3142	7110
  		homolog, subfamily
  		B,member 4
  NM_007043	HRB2	HIV-1 rev binding		3143	7111
  		protein 2
  NM_007054	KIF3A	kinesin family	Motor protein, Microtubule, ATP-	3144	7112
  		member 3A	binding, Coiled coil, Neurone
  NM_007056	SWAP2	splicing factor,	mRNA processing, mRNA splicing,	3145	7113
  		arginine/serine-rich	Nuclear protein, Alternative splicing,
  		16 (suppressor-of-	Polymorphism
  		white-apricot
  		homolog,
  		Drosophila)
  NM_007059	KPTN	kaptin (actin binding		3146	7114
  		protein)
  NM_007062	PWP1	nuclear	Repeat, WD repeat, Nuclear protein,	3147	7115
  		phosphoprotein	Phosphorylation
  		similar toS. cerevisiae
  		PWP1
  NM_007063	TBC1D8	TBC1 domain family,	GTPase activation	3148	7116
  		member 8 (with
  		GRAM domain)
  NM_007065	CDC37	CDC37 cell division	Chaperone	3149	7117
  		cycle 37 homolog (S. cerevisiae)
  NM_007070	FAP48	glomulin, FKBP	Coiled coil, Phosphorylation,	3150	7118
  		associated protein	Alternative splicing, Disease
  			mutation, Polymorphism
  NM_007074	CORO1A	coronin, actin	Actin-binding, Repeat, WD repeat,	3151	7119
  		binding protein, 1A	Coiled coil, Polymorphism
  NM_007077	AP4S1	adaptor-related	Coated pits, Endocytosis	3152	7120
  		protein complex 4,
  		sigma 1 subunit
  NM_007098	CLTCL1	clathrin, heavy	Coated pits, Alternative splicing	3153	7121
  		polypeptide-like 1
  NM_007099	ACP1	acid phosphatase	1,	Hydrolase, Acetylation, Alternative	3154	7122
  		soluble	splicing, Polymorphism, 3D-structure
  NM_007108	TCEB2	transcription	Transcription regulation, Ubl	3155	7123
  		elongation factor B	conjugation pathway, Nuclear
  		(SIII),polypeptide 2	protein, 3D-structure
  		(18 kDa, elongin B)
  NM_007115	TNFAIP6	tumor necrosis	Cell adhesion, Signal, Glycoprotein,	3156	7124
  		factor, alpha-induced	Polymorphism, 3D-structure
  		protein
  6
  NM_007145	ZNF146	zinc finger protein	Zinc-finger, DNA-binding, Metal-	3157	7125
  		146	binding, Nuclear protein, Repeat
  NM_007152	ZNF195	zinc finger protein	Zinc-finger, Metal-binding, DNA-	3158	7126
  		195	binding, Nuclear protein, Alternative
  			splicing
  NM_007161	LST1	leukocyte specific	Signal, Immune response, Cell	3159	7127
  		transcript 1	shape, Transmembrane, Alternative
  			splicing, Receptor
  NM_007169	PEMT	phosphatidylethanol	Phospholipid biosynthesis,	3160	7128
  		amine N-	Transferase, Methyltransferase,
  		methyltransferase	Transmembrane, Mitochondrion,
  			Endoplasmic reticulum,
  			Polymorphism
  NM_007172	NUP50	nucleoporin	50 kDa	Hypothetical protein, Nuclear	3161	7129
  			protein, Transport, Protein transport,
  			Repeat, Porin
  NM_007178	UNRIP	unr-interacting	Hypothetical protein, Repeat, WD	3162	7130
  		protein	repeat
  NM_007186	CEP2	centrosomal protein 2	Cell cycle, Coiled coil,	3163	7131
  			Phosphorylation, Alternative splicing,
  			Polymorphism
  NM_007205	TREX2	three prime repair	Hypothetical protein, Proteasome,	3164	7132
  		exonuclease 2	Exonuclease
  NM_007208	MRPL3	mitochondrial	Ribosomal protein, Mitochondrion	3165	7133
  		ribosomal protein L3
  NM_007212	RNF2	ring finger protein 2	Metal-binding, Zinc, Zinc-finger	3166	7134
  NM_007213	JM4	JM4 protein		3167	7135
  NM_007219	RNF24	ring finger protein 24	Zinc-finger	3168	7136
  NM_007222	ZHX1	zinc-fingers and	Homeobox, Metal-binding, Nuclear	3169	7137
  		homeoboxes 1	protein, Zinc, Zinc-finger
  NM_007238	PXMP4	peroxisomal	Peroxisome, Transmembrane,	3170	7138
  		membrane protein 4,	Glycoprotein, Polymorphism
  		24 kDa
  NM_007240	DUSP12	dual specificity	Hydrolase, Zinc, Metal-binding	3171	7139
  		phosphatase 12
  NM_007248	TREX1	three prime repair	Hypothetical protein, Exonuclease	3172	7140
  		exonuclease 1
  NM_007255	B4GALT7	xylosylprotein beta	Glycosyltransferase, Transferase,	3173	7141
  		1,4-	Glycoprotein, Transmembrane,
  		galactosyltransferase,	Signal-anchor, Golgi stack,
  		polypeptide 7	Multigene family, Disease mutation,
  		(galactosyltransferase	Ehlers-Danlos syndrome
  		I)
  NM_007274	BACH	brain acyl-CoA	Hydrolase, Serine esterase, Repeat,	3174	7142
  		hydrolase	Alternative splicing
  NM_007278	GABARAP	GABA(A) receptor-	Receptor	3175	7143
  		associated protein
  NM_007284	PTK9L	protein tyrosine	Hypothetical protein, Kinase	3176	7144
  		kinase 9-like (A6-
  		related protein)
  NM_007311	BZRP	benzodiazapine	Mitochondrion, Receptor,	3177	7145
  		receptor (peripheral)	Transmembrane, Polymorphism
  NM_007317	KIF22	kinesin family	DNA-binding, Motor protein,	3178	7146
  		member 22	Microtubule, ATP-binding, Coiled
  			coil, Nuclear protein
  NM_007318	PSEN1	presenilin 1	Transmembrane, Phosphorylation,	3179	7147
  		(Alzheimer disease	Endoplasmic reticulum, Golgi stack,
  		3)	Alzheimer's disease, Disease
  			mutation, Polymorphism, Alternative
  			splicing
  NM_007320	RANBP3	RAN binding protein 3	Hypothetical protein	3180	7148
  NM_007334	KLRD1	killer cell lectin-like	Antigen, Receptor, Glycoprotein,	3181	7149
  		receptor subfamily	Transmembrane, Signal-anchor,
  		D,member 1	Lectin, Alternative splicing, 3D-
  			structure
  NM_007346	OGFR	opioid growth factor	Receptor, Growth regulation,	3182	7150
  		receptor	Repeat, Alternative splicing
  NM_007360	D12S2489E	killer cell lectin-like	Receptor, Transmembrane,	3183	7151
  		receptor subfamily	Multigene family, Signal-anchor,
  		K,member 1	Lectin, Glycoprotein, Polymorphism,
  			3D-structure
  NM_007375	TARDBP	TAR DNA binding	DNA-binding, RNA-binding, Nuclear	3184	7152
  		protein	protein, Transcription regulation,
  			Repressor, mRNA processing,
  			mRNA splicing, Repeat
  NM_009588	LTB	lymphotoxin beta	Cytokine, Transmembrane,	3185	7153
  		(TNF superfamily,	Glycoprotein, Signal-anchor,
  		member 3)	Alternative splicing, Polymorphism
  NM_012062	DNM1L	dynamin 1-like	Hypothetical protein	3186	7154
  NM_012064	MIP	major intrinsic	Gap junction, Transport,	3187	7155
  		protein of lens fiber	Transmembrane, Phosphorylation,
  			Eye lens protein
  NM_012079	DGAT1	diacylglycerol O-	Transferase, Acyltransferase,	3188	7156
  		acyltransferase	Transmembrane, Endoplasmic
  		homolog 1 (mouse)	reticulum, Hypothetical protein
  NM_012084	GLUD2	glutamate	Hypothetical protein	3189	7157
  		dehydrogenase 2
  NM_012086	GTF3C3	general transcription	Hypothetical protein	3190	7158
  		factor IIIC,
  		polypeptide 3,
  		102 kDa
  NM_012089	ABCB10	ATP-binding	ATP-binding, Transmembrane,	3191	7159
  		cassette, sub-family	Transport, Mitochondrion, Inner
  		B (MDR/TAP),	membrane, Transit peptide,
  		member 10	Polymorphism
  NM_012094	PRDX5	peroxiredoxin 5	Antioxidant, Peroxisome,	3192	7160
  			Mitochondrion, Transit peptide,
  			Alternative initiation, Polymorphism,
  			3D-structure
  NM_012100	DNPEP	aspartyl	Hydrolase, Aminopeptidase,	3193	7161
  		aminopeptidase	Metalloprotease, Zinc, Hypothetical
  			protein
  NM_012108	BRDG1	BCR downstream		3194	7162
  		signaling 1
  NM_012114	CASP14	caspase 14,	Hydrolase, Thiol protease,	3195	7163
  		apoptosis-related	Apoptosis, Zymogen
  		cysteine protease
  NM_012124	CHORDC1	cysteine and		3196	7164
  		histidine-rich domain
  		(CHORD)-
  		containing,zinc
  		binding protein
  1
  NM_012130	CLDN14	claudin 14	Tight junction, Transmembrane,	3197	7165
  			Polymorphism, Disease mutation,
  			Deafness
  NM_012142	CCNDBP1	cyclin D-type	Cyclin, Hypothetical protein	3198	7166
  		binding-protein 1
  NM_012143	TFIP11	tuftelin interacting	Biomineralization, Nuclear protein,	3199	7167
  		protein 11	Alternative splicing
  NM_012151	F8A	coagulation factor	Hypothetical protein	3200	7168
  		VIII-associated
  		(intronic transcript)
  NM_012168	FBXO2	F-box onlyprotein 2	Ubl conjugation pathway	3201	7169
  NM_012185	FOXE2	forkhead box E2	DNA-binding, Nuclear protein,	3202	7170
  			Transcription regulation
  NM_012198	GCA	grancalcin, EF-hand	Calcium-binding, Repeat, 3D-	3203	7171
  		calcium binding	structure
  		protein
  NM_012203	GRHPR	glyoxylate	Hypothetical protein,	3204	7172
  		reductase/hydroxypyruvate	Oxidoreductase, Pyruvate
  		reductase
  NM_012214	MGAT4A	mannosyl (alpha-	Glycosyltransferase, Transferase	3205	7173
  		1,3-)-glycoprotein
  		beta-1,4-N-
  		acetylglucosaminyltransferase,
  		isoenzyme A
  NM_012218	ILF3	interleukin enhancer	Hypothetical protein, Transcription	3206	7174
  		bindingfactor 3,	regulation, DNA-binding, RNA-
  		90 kDa	binding, Nuclear protein, Repeat,
  			Phosphorylation, Methylation,
  			Alternative splicing
  NM_012228	PILB	pilin-like transcription	Hypothetical protein	3207	7175
  		factor
  NM_012229	NT5C2	5′-nucleotidase,	Hydrolase, Allosteric enzyme	3208	7176
  		cytosolic II
  NM_012236	SCMH1	sex comb on midleg		3209	7177
  		homolog 1
  		(Drosophila)
  NM_012244	SLC7A8	solute carrier family	Hypothetical protein, Transport,	3210	7178
  		7 (cationic amino	Amino-acid transport,
  		acid transporter, y+	Transmembrane
  		system),member 8
  NM_012250	RRAS2	related RAS viral (r-	GTP-binding, Prenylation,	3211	7179
  		ras) oncogene	Lipoprotein, Proto-oncogene,
  		homolog 2	Diseasemutation
  NM_012255	XRN2
  	5′-3′	mRNA processing, Hydrolase,	3212	7180
  		exoribonuclease 2	Nuclease, Exonuclease, Nuclear
  			protein, RNA-binding, Zinc-finger
  NM_012258	HEY1	hairy/enhancer-of-	Hypothetical protein, Transcription	3213	7181
  		split related with	regulation, DNA-binding,Nuclear
  		YRPW motif
  1	protein
  NM_012262	HS2ST1	heparan sulfate 2-O-	Hypothetical protein, Transferase	3214	7182
  		sulfotransferase 1
  NM_012282	KCNE1L	potassium voltage-	Transmembrane, Glycoprotein,	3215	7183
  		gated channel, lsk-	Alport syndrome, Deafness,
  		related family,	Elliptocytosis
  		member 1-like
  NM_012286	MORF4L2	mortality factor	4 like 2	Growth regulation, Nuclear protein	3216	7184
  NM_012290	TLK1	tousled-like kinase 1	ATP-binding, Kinase,	3217	7185
  			Serine/threonine-protein kinase,
  			Transferase, Chromatin regulator,
  			Cell cycle, DNA damage, Nuclear
  			protein, Coiled coil, Phosphorylation,
  			Alternative splicing
  NM_012295	CABIN1	calcineurin binding	Hypothetical protein,	3218	7186
  		protein 1	Phosphorylation, Repeat, TPR
  			repeat
  NM_012329	MMD	monocyte to	Transmembrane	3219	7187
  		macrophage
  		differentiation-
  		associated
  NM_012331	MSRA	methionine sulfoxide	Oxidoreductase	3220	7188
  		reductase A
  NM_012341	CRFG	GTPbinding protein 4	GTP-binding,Nuclear protein	3221	7189
  NM_012342	NMA	putative	Transmembrane, Signal,	3222	7190
  		transmembrane	Glycoprotein
  		protein
  NM_012343	NNT	nicotinamide	Oxidoreductase, NAD, NADP,	3223	7191
  		nucleotide	Transmembrane, Mitochondrion,
  		transhydrogenase	Transit peptide, 3D-structure,
  			Hypothetical protein
  NM_012347	FBXO9	F-box onlyprotein 9	Hypothetical protein, Ubl conjugation	3224	7192
  			pathway, TPR repeat
  NM_012383	OSTF1	osteoclast	Hypothetical protein, ANK repeat,	3225	7193
  		stimulatingfactor 1	Repeat, SH3 domain
  NM_012384	GMEB2	glucocorticoid	Trans-acting factor, Nuclear protein,	3226	7194
  		modulatory element	DNA-binding, Coiledcoil
  		binding protein
  2
  NM_012387	PADI4	peptidyl arginine	Hydrolase, Calcium-binding,	3227	7195
  		deiminase, type IV	Multigene family
  NM_012390	PROL5	proline rich 5	Saliva	3228	7196
  		(salivary)
  NM_012392	PEF	PEF protein with a	Calcium-binding	3229	7197
  		long N-terminal
  		hydrophobic domain
  		(peflin)
  NM_012400	PLA2G2D	phospholipase A2,	Hydrolase, Lipid degradation, Signal,	3230	7198
  		group IID	Calcium, Polymorphism
  NM_012403	ANP32C	acidic (leucine-rich)		3231	7199
  		nuclear
  		phosphoprotein 32
  		family, member C
  NM_012413	QPCT	glutaminyl-peptide	Transferase, Acyltransferase, Signal,	3232	7200
  		cyclotransferase	Polymorphism
  		(glutaminyl cyclase)
  NM_012434	SLC17A5	solute carrier family	Transmembrane, Hypothetical	3233	7201
  		17 (anion/sugar	protein, Sugar transport
  		transporter),
  		member 5
  NM_012445	SPON2	spondin	2,	Hypothetical protein, Matrix protein	3234	7202
  		extracellular matrix
  		protein
  NM_012446	SSBP2	single-stranded DNA	DNA-binding, Nuclear protein	3235	7203
  		bindingprotein 2
  NM_012455	TIC	SEC7 homolog		3236	7204
  NM_012460	TIMM9	translocase of inner	Transport, Protein transport,	3237	7205
  		mitochondrial	Translocation, Mitochondrion, Inner
  		membrane 9	membrane, Hypothetical protein
  		homolog (yeast)
  NM_012463	ATP6V0A2	ATPase, H+	Hydrogen ion transport,	3238	7206
  		transporting,	Transmembrane, Glycoprotein,
  		lysosomal V0	Hypothetical protein
  		subunit aisoform 2
  NM_012483	GNLY	granulysin	Antibiotic, Fungicide, Signal, T-cell,	3239	7207
  			Alternative splicing, 3D-structure
  NM_012484	HMMR	hyaluronan-	Hyaluronic acid, Alternative splicing,	3240	7208
  		mediated motility	Repeat, Glycoprotein, Antigen
  		receptor (RHAMM)
  NM_012485	HMMR	hyaluronan-	Hyaluronic acid, Alternative splicing,	3241	7209
  		mediated motility	Repeat, Glycoprotein, Antigen
  		receptor (RHAMM)
  NM_013229	APAF1	apoptotic protease	Apoptosis, ATP-binding, Repeat,	3242	7210
  		activating factor	WD repeat, Alternative splicing, 3D-
  			structure
  NM_013235	RNASE3L	nuclear RNase III	Ribosome biogenesis, Hydrolase,	3243	7211
  		Drosha	Nuclease, Endonuclease, Repeat,
  			RNA-binding, Nuclear protein,
  			Alternative splicing
  NM_013236	E46L	like mouse brain	Hypothetical protein	3244	7212
  		protein E46
  NM_013242	GTL3	likely ortholog of		3245	7213
  		mousegene trap
  		locus
  3
  NM_013248	NXT1	NTF2-like export	Transport, Protein transport, Nuclear	3246	7214
  		factor 1	protein, 3D-structure
  NM_013252	CLECSF5	C-type (calcium	Transmembrane, Lectin	3247	7215
  		dependent,
  		carbohydrate-
  		recognition domain)
  		lectin,superfamily
  		member
  5
  NM_013258	ASC	apoptosis-	Apoptosis, Anti-oncogene,	3248	7216
  		associated speck-	Alternative splicing
  		like protein
  		containing a CARD
  NM_013259	NP25	neuronal protein		3249	7217
  NM_013272	SLC21A11	solute carrier organic	Transmembrane, Transport, Ion	3250	7218
  		anion transporter	transport, Glycoprotein
  		family, member 3A1
  NM_013285	HUMAUANTIG	nucleolar GTPase	GTP-binding, Nuclear protein	3251	7219
  NM_013286	KIAA0800	chromosome 3p21.1	Hypothetical protein	3252	7220
  		gene sequence
  NM_013289	KIR3DL1	killer cell	Receptor, Immunoglobulin domain,	3253	7221
  		immunoglobulin-like	Glycoprotein, Signal,
  		receptor, three	Transmembrane, Repeat, Multigene
  		domains, long	family, Polymorphism, 3D-structure,
  		cytoplasmic tail, 1	Alternative splicing
  NM_013296	MCLC	LGN protein	Hypothetical protein, Repeat, TPR	3254	7222
  			repeat, Phosphorylation
  NM_013300	HSU79274	protein predicted by	Hypothetical protein	3255	7223
  		clone 23733
  NM_013301	HSU79303	protein predicted by	Hypothetical protein	3256	7224
  		clone 23882
  NM_013312	HOOK2	hook homolog 2	Hypothetical protein	3257	7225
  		(Drosophila)
  NM_013319	TERE1	transitional epithelia		3258	7226
  		response protein
  NM_013323	SNX11	sorting nexin 11	Transport, Protein transport	3259	7227
  NM_013328	P5CR2	pyrroline 5-	Hypothetical protein	3260	7228
  		carboxylate
  		reductase isoform
  NM_013330	NME7	non-metastatic cells	Transferase, Kinase, ATP-binding,	3261	7229
  		7, protein expressed	Sodium/potassium transport,
  		in (nucleoside-	Transmembrane, Glycoprotein,
  		diphosphate kinase)	Multigene family, Signal-anchor,
  			Alternative splicing
  NM_013341	PTD004	hypothetical protein	GTP-binding, Alternative splicing	3262	7230
  		PTD004
  NM_013351	TBX21	T-box 21	Transcription regulation, DNA-	3263	7231
  			binding, Nuclear protein, Activator
  NM_013354	CNOT7	CCR4-NOT	Transcription regulation, Repressor,	3264	7232
  		transcription	Nuclear protein, Hypothetical protein
  		complex, subunit 7
  NM_013363	PCOLCE2	procollagen C-	Collagen	3265	7233
  		endopeptidase
  		enhancer
  2
  NM_013364	PNMA3	paraneoplastic	Hypothetical protein	3266	7234
  		antigen MA3
  NM_013368	RBT1	RPA-binding trans-	Hypothetical protein	3267	7235
  		activator
  NM_013382	POMT2	protein-O-	Transferase, Glycosyltransferase,	3268	7236
  		mannosyltransferase 2	Endoplasmic reticulum,
  			Transmembrane, Glycoprotein,
  			Repeat, Alternative splicing
  NM_013383	TCFL4	transcription factor-	Transcription regulation, Repressor,	3269	7237
  		like 4	Nuclear protein, DNA-binding,
  			Alternative splicing, Receptor
  NM_013392	NRBP	nuclear receptor	Hypothetical protein, ATP-binding,	3270	7238
  		binding protein	Transferase, Nuclear protein,
  			Receptor
  NM_013395	AD013	Homo sapiens	Hypothetical protein,	3271	7239
  		proteinx0008	Transmembrane
  		(AD013) mRNA,
  		complete cds.
  NM_013403	STRN4	striatin, calmodulin	Calmodulin-binding, Repeat, WD	3272	7240
  		bindingprotein 4	repeat, Coiled coil
  NM_013412	RABL2A	RAB, member of	Hypothetical protein, GTP-binding,	3273	7241
  		RAS oncogene	Alternative splicing
  		family-like 2A
  NM_013416	NCF4	neutrophil cytosolic	SH3 domain, Alternative splicing,	3274	7242
  		factor 4, 40 kDa	3D-structure
  NM_013421	GGT1	gamma-	Glutathione biosynthesis,	3275	7243
  		glutamyltransferase 1	Transferase, Acyltransferase,
  			Signal-anchor, Transmembrane,
  			Zymogen, Glycoprotein, Sialic acid,
  			Alternative splicing, Alternative
  			promoter usage
  NM_013430	GGT1	gamma-	Glutathione biosynthesis,	3276	7244
  		glutamyltransferase 1	Transferase, Acyltransferase,
  			Signal-anchor, Transmembrane,
  			Zymogen, Glycoprotein, Sialic acid,
  			Alternative splicing, Alternative
  			promoter usage
  NM_013439	PILR(ALPHA)	paired	Receptor	3277	7245
  		immunoglobin-like
  		type
  2 receptor
  		alpha
  NM_013440	PILR(BETA)	paired	Meiosis, Cell cycle, Chromosome	3278	7246
  		immunoglobin-like	partition, Nuclear protein,Alternative
  		type
  2 receptor beta	splicing, Hypothetical protein,
  			Receptor
  NM_013444	UBQLN2	ubiquilin	2	Hypothetical protein	3279	7247
  NM_013448	BAZ1A	bromodomain	Transcription regulation,	3280	7248
  		adjacent to zinc	Bromodomain, Zinc-finger, Coiled
  		finger domain, 1A	coil, Nuclear protein, Alternative
  			splicing
  NM_013940	OR10H1	olfactory receptor,		3281	7249
  		family 10, subfamily
  		H,member 1
  NM_013943	CLIC4	chloride intracellular	Hypothetical protein, Ionic channel,	3282	7250
  		channel 4	Ion transport, Chloride channel,
  			Voltage-gated channel
  NM_013951	PAX8	pairedbox gene 8	DNA-binding, Developmental	3283	7251
  			protein, Nuclear protein, Paired box,
  			Transcription, Transcription
  			regulation, Differentiation, Alternative
  			splicing, Disease mutation,
  			Polymorphism
  NM_013956	NRG1	neuregulin 1	EGF-like domain, Growth factor,	3284	7252
  			Transmembrane, Multigene family,
  			Alternative splicing, Immunoglobulin
  			domain, Glycoprotein,
  			Polymorphism, 3D-structure,
  			Chromosomal translocation
  NM_013974	DDAH2	dimethylarginine	Hydrolase	3285	7253
  		dimethylaminohydrolase 2
  NM_013975	LIG3	ligase III, DNA, ATP-	DNA repair, DNA replication, DNA	3286	7254
  		dependent	recombination, Cell division, Ligase,
  			ATP-binding, Zinc-finger, Nuclear
  			protein, Alternative splicing, 3D-
  			structure, Hypothetical protein
  NM_013979	BNIP1	BCL2/adenovirus	Apoptosis, Alternative splicing,	3287	7255
  		E1B 19 kDa	Transmembrane
  		interacting protein
  1
  NM_013992	PAX8	pairedbox gene 8	DNA-binding, Developmental	3288	7256
  			protein, Nuclear protein, Paired box,
  			Transcription, Transcription
  			regulation, Differentiation, Alternative
  			splicing, Disease mutation,
  			Polymorphism
  NM_013995	LAMP2	lysosomal-	Transmembrane, Glycoprotein,	3289	7257
  		associated	Lysosome, Signal,Alternative
  		membrane protein
  2	splicing, Polymorphism
  NM_014000	VCL	vinculin	Cell adhesion, Actin-binding,	3290	7258
  			Cytoskeleton, Structural protein,
  			Phosphorylation, Repeat, Alternative
  			splicing, Lipoprotein
  NM_014011	SOCS5	suppressor of	SH2 domain, Growth regulation,	3291	7259
  		cytokine signaling 5	Signal transduction inhibitor
  NM_014018	MRPS28	mitochondrial	Ribosomal protein, Mitochondrion	3292	7260
  		ribosomal protein
  		S28
  NM_014029	RAC2	ras-related C3	GTP-binding, Prenylation,	3293	7261
  		botulinum toxin	Lipoprotein, 3D-structure
  		substrate 2 (rho
  		family, small GTP
  		binding protein
  		Rac2)
  NM_014030	GIT1	G protein-coupled	Hypothetical protein, GTPase	3294	7262
  		receptor kinase-	activation, Repeat, ANK repeat,
  		interactor 1	Zinc-finger
  NM_014038	BZW2	basic leucine zipper	Hypothetical protein	3295	7263
  		andW2 domains 2
  NM_014042	DKFZP564M082	DKFZP564M082	Hypothetical protein	3296	7264
  		protein
  NM_014050	MRPL42	mitochondrial	Ribosomal protein, Mitochondrion	3297	7265
  		ribosomal protein
  		L42
  NM_014051	PTD011	transmembrane	Transmembrane	3298	7266
  		protein 14A
  NM_014052	GW128	GW128 protein		3299	7267
  NM_014055	CDV-1	carnitine deficiency-	Hypothetical protein	3300	7268
  		associated gene
  		expressed in
  		ventricle 1
  NM_014056	HIG1	likely ortholog of	Hypothetical protein	3301	7269
  		mouse hypoxia
  		inducedgene 1
  NM_014060	MCT-1	malignant T cell		3302	7270
  		amplifiedsequence 1
  NM_014061	MAGEH1	APR-1 protein	Antigen	3303	7271
  NM_014062	ART-4	likely ortholog of	Hypothetical protein	3304	7272
  		mouse nin one
  		binding protein
  NM_014063	HIP-55	src homology 3	Hypothetical protein, SH3 domain	3305	7273
  		domain-containing
  		protein HIP-55
  NM_014078	MRPL13	mitochondrial	Ribosomal protein, Mitochondrion	3306	7274
  		ribosomal protein
  		L13
  NM_014080	DUOX2	dual oxidase 2	Peroxidase	3307	7275
  NM_014147	CAPRI	HSPC047 protein	GTPase activation, Repeat	3308	7276
  NM_014165	C6orf66	chromosome 6 open		3309	7277
  		reading frame 66
  NM_014170	HSPC135	HSPC135 protein	Hypothetical protein	3310	7278
  NM_014175	MRPL15	mitochondrial	Hypothetical protein	3311	7279
  		ribosomal protein
  		L15
  NM_014177	HSPC154	HSPC154 protein		3312	7280
  NM_014180	MRPL22	mitochondrial	Hypothetical protein, Ribosomal	3313	7281
  		ribosomal protein	protein
  		L22
  NM_014182	ORMDL2	ORM1-like 2 (S. cerevisiae)	Hypothetical protein, Nuclear	3314	7282
  			protein, DNA-binding, Transcription,
  			Transcription regulation, Translation
  			regulation, Receptor
  NM_014184	HSPC163	HSPC163 protein	Hypothetical protein,	3315	7283
  			Transmembrane
  NM_014204	BOK	Homo sapiensBcl-2		3316	7284
  		related ovarian killer
  		(BOK) mRNA,
  		complete cds.
  NM_014207	CD5	CD5 antigen (p56-62)	Signal, Transmembrane,	3317	7285
  			Glycoprotein, T-cell, Repeat
  NM_014214	IMPA2	inositol(myo)-1(or 4)-	Hydrolase	3318	7286
  		monophosphatase 2
  NM_014216	ITPK1	inositol 1,3,4-	Kinase, Hypothetical protein	3319	7287
  		triphosphate 5/6
  		kinase
  NM_014221	MTCP1	mature T-cell	Proto-oncogene, Mitochondrion,	3320	7288
  		proliferation 1	Alternative splicing, Chromosomal
  			translocation, 3D-structure
  NM_014223	NFYC	nuclear transcription	Transcription regulation, DNA-	3321	7289
  		factor Y, gamma	binding, Activator, Nuclear protein,
  			Alternative splicing, 3D-structure
  NM_014225	PPP2R1A	protein phosphatase	Hypothetical protein, Multigene	3322	7290
  		2 (formerly 2A),	family, Acetylation, Repeat,
  		regulatory subunit A	Polymorphism, 3D-structure
  		(PR 65), alpha
  		isoform
  NM_014231	VAMP1	vesicle-associated	Mitochondrion, Synapse,	3323	7291
  		membrane protein 1	Synaptosome, Transmembrane,
  		(synaptobrevin 1)	Coiled coil, Alternative splicing,
  			Multigene family
  NM_014232	VAMP2	vesicle-associated	Hypothetical protein, Synapse,	3324	7292
  		membrane protein 2	Synaptosome, Transmembrane,
  		(synaptobrevin 2)	Coiled coil, Acetylation, Multigene
  			family, 3D-structure
  NM_014239	EIF2B2	eukaryotic	Initiation factor, Protein biosynthesis,	3325	7293
  		translation initiation	Disease mutation
  		factor 2B,subunit 2
  		beta, 39 kDa
  NM_014241	PTPLA	protein tyrosine	ATP-binding, Chaperone	3326	7294
  		phosphatase-like
  		(proline instead of
  		catalytic arginine),
  		member a
  NM_014242	ZNF237	zinc finger protein		3327	7295
  		237
  NM_014245	RNF7	ring finger protein 7	Ubl conjugation pathway, Zinc, Zinc-	3328	7296
  			finger, Metal-binding,
  			Phosphorylation, Alternative splicing
  NM_014252	SLC25A15	solute carrier family	Mitochondrion, Inner membrane,	3329	7297
  		25 (mitochondrial	Repeat, Transmembrane, Transport,
  		carrier; ornithine	Disease mutation, Polymorphism
  		transporter)member
  		15
  NM_014253	ODZ1	odz, odd Oz/ten-m	EGF-like domain	3330	7298
  		homolog
  		1(Drosophila)
  NM_014254	TMEM5	transmembrane	Transmembrane	3331	7299
  		protein 5
  NM_014268	MAPRE2	microtubule-	T-cell	3332	7300
  		associated protein,
  		RP/EB family,
  		member 2
  NM_014280	DNAJC8	DnaJ (Hsp40)	Chaperone	3333	7301
  		homolog, subfamily
  		C,member 8
  NM_014292	CBX6	chromobox homolog 6	Chromatin regulator, Nuclear	3334	7302
  			protein, Transcription regulation,
  			Repressor
  NM_014297	YF13H12	ethylmalonic		3335	7303
  		encephalopathy 1
  NM_014306	HSPC117	hypothetical protein	Hypothetical protein	3336	7304
  		HSPC117
  NM_014313	SMP1	small membrane	Transmembrane, Polymorphism	3337	7305
  		protein 1
  NM_014326	DAPK2	death-associated	Transferase, Serine/threonine-	3338	7306
  		protein kinase 2	protein kinase, Calmodulin-binding,
  			Phosphorylation, ATP-binding,
  			Apoptosis
  NM_014330	PPP1R15A	protein phosphatase	Hypothetical protein	3339	7307
  		1, regulatory
  		(inhibitor) subunit
  		15A
  NM_014335	CRI1	CREBBP/EP300	Hypothetical protein	3340	7308
  		inhibitory protein 1
  NM_014339	IL17R	interleukin 17	Receptor, Transmembrane, Signal,	3341	7309
  		receptor	Glycoprotein
  NM_014341	MTCH1	mitochondrial carrier		3342	7310
  		homolog 1 (C. elegans)
  NM_014343	CLDN15	claudin 15	Tight junction, Transmembrane	3343	7311
  NM_014350	GG2-1	TNF-induced protein		3344	7312
  NM_014357	XP5	small proline rich-like		3345	7313
  		(epidermal
  		differentiation
  		complex) 1B
  NM_014359	OPTC	opticin	Glycoprotein, Extracellular matrix,	3346	7314
  			Signal, Repeat, Leucine-rich repeat,
  			Sulfation
  NM_014362	HIBCH	3-hydroxyisobutyryl-	Hydrolase	3347	7315
  		Coenzyme A
  		hydrolase
  NM_014366	E2IG3	nucleostemin	Hypothetical protein	3348	7316
  NM_014373	GPCR1	G protein-coupled	Receptor	3349	7317
  		receptor 160
  NM_014381	MLH3	mutL homolog 3 (E. coli)	DNA repair, Nuclear protein,	3350	7318
  			Polymorphism, Alternative splicing,
  			Hereditary nonpolyposis colorectal
  			cancer, Disease mutation,
  			Hypothetical protein
  NM_014399	NET-6	transmembrane 4	Glycoprotein, Transmembrane	3351	7319
  		superfamily member
  		13
  NM_014403	SIAT7D	sialyltransferase 7D	Transferase, Glycosyltransferase,	3352	7320
  		((alpha-N-	Glycoprotein, Transmembrane,
  		acetylneuraminyl-	Signal-anchor, Golgistack
  		2,3-beta-galactosyl-
  		1,3)-N-acetyl
  		galactosaminide
  		alpha-2,6-
  		sialyltransferase)
  NM_014413	HRI	heme-regulated	Transferase, Kinase,	3353	7321
  		initiation factor 2-	Serine/threonine-protein kinase,
  		alpha kinase	Protein synthesis inhibitor, ATP-
  			binding, Repeat, Phosphorylation,
  			Alternative splicing, Polymorphism,
  			Protein biosynthesis
  NM_014425	INVS	inversin	ANK repeat, Repeat	3354	7322
  NM_014426	SNX5	sorting nexin 5	Transport, Protein transport,	3355	7323
  			Hypothetical protein
  NM_014430	CIDEB	cell death-inducing	Apoptosis, 3D-structure, RNA-	3356	7324
  		DFFA-like effector b	binding, Repeat, G-protein coupled
  			receptor, Transmembrane,
  			Glycoprotein
  NM_014434	NR1	NADPH-dependent		3357	7325
  		FMN and FAD
  		containing
  		oxidoreductase
  NM_014437	SLC39A1	solute carrier family	Transport, Zinc transport,	3358	7326
  		39 (zinc transporter),	Transmembrane
  		member 1
  NM_014446	MIBP	integrin beta 1		3359	7327
  		bindingprotein 3
  NM_014450	SIT	SHP2-interacting	Signal	3360	7328
  		transmembrane
  		adaptor protein
  NM_014453	BC-2	putative breast		3361	7329
  		adenocarcinoma
  		marker (32 kD)
  NM_014465	SULT1B1	sulfotransferase	Hypothetical protein, Transferase	3362	7330
  		family, cytosolic, 1B,
  		member 1
  NM_014473	HSA9761	putative	rRNA processing, Transferase,	3363	7331
  		dimethyladenosine	Methyltransferase
  		transferase
  NM_014481	APEX2	APEX nuclease	Endonuclease	3364	7332
  		(apurinic/apyrimidinic
  		endonuclease) 2
  NM_014499	P2RY10	purinergic receptor	Receptor, Transmembrane	3365	7333
  		P2Y, G-protein
  		coupled, 10
  NM_014503	DRIM	down-regulated in		3366	7334
  		metastasis
  NM_014517	UBP1	upstream binding	Hypothetical protein	3367	7335
  		protein 1 (LBP-1a)
  NM_014520	MYBBP1A	MYB binding protein	Hypothetical protein	3368	7336
  		(P160) 1a
  NM_014575	SCHIP1	schwannomin	Hypothetical protein	3369	7337
  		interactingprotein 1
  NM_014593	CGBP	CpG binding protein	Hypothetical protein, Transcription	3370	7338
  			regulation, Activator, DNA-binding,
  			Zinc-finger, Metal-binding, Coiled
  			coil, Nuclear protein
  NM_014624	S100A6	S100 calcium	Mitogen, Cell cycle, Calcium-binding,	3371	7339
  		binding protein A6	Polymorphism, 3D-structure
  		(calcyclin)
  NM_014630	KIAA0211	KIAA0211 gene	Hypothetical protein, Transcription	3372	7340
  		product	regulation, DNA-binding, Zinc-finger,
  			Metal-binding, Nuclear protein,
  			Repeat
  NM_014638	KIAA0450	KIAA0450 gene	Hypothetical protein	3373	7341
  		product
  NM_014639	KIAA0372	KIAA0372	Hypothetical protein	3374	7342
  NM_014659	KIAA0377	KIAA0377 gene	Hypothetical protein	3375	7343
  		product
  NM_014671	KIAA0010	ubiquitin-protein	Hypothetical protein, Ligase	3376	7344
  		isopeptide ligase
  		(E3)
  NM_014675	KIAA0445	ciliary rootlet coiled-	Hypothetical protein	3377	7345
  		coil, rootletin
  NM_014678	KIAA0685	KIAA0685	Hypothetical protein	3378	7346
  NM_014684	KIAA0373	KIAA0373 gene	Hypothetical protein, Coiled coil	3379	7347
  		product
  NM_014685	HERPUD1	homocysteine-	Hypothetical protein, Unfolded	3380	7348
  		inducible,	protein response, Endoplasmic
  		endoplasmic	reticulum, Transmembrane,
  		reticulum stress-	Alternative splicing
  		inducible, ubiquitin-
  		like domain member 1
  NM_014688	RNTRE	USP6 N-terminal like	Hypothetical protein	3381	7349
  NM_014698	KIAA0792	KIAA0792 gene	Hypothetical protein	3382	7350
  		product
  NM_014699	KIAA0296	KIAA0296 gene	Hypothetical protein, Transcription	3383	7351
  		product	regulation, DNA-binding, Zinc-finger,
  			Metal-binding, Nuclear protein,
  			Repeat
  NM_014707	HDAC9	histone deacetylase	9	Hydrolase, Nuclear protein,	3384	7352
  			Chromatin regulator, Transcription
  			regulation, Repressor, Alternative
  			splicing, Hypothetical protein
  NM_014710	KIAA0443	G protein-coupled	Hypothetical protein	3385	7353
  		receptor-associated
  		sorting protein
  NM_014716	CENTB1	centaurin,beta 1	GTPase activation, Repeat, ANK	3386	7354
  			repeat, Zinc-finger
  NM_014718	CLSTN3	calsyntenin	3	Cell adhesion, Glycoprotein,	3387	7355
  			Transmembrane, Calcium-binding,
  			Repeat, Signal
  NM_014724	ZNF305	zinc finger protein	Transcription regulation, DNA-	3388	7356
  		305	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  NM_014727	WBP7	myeloid/lymphoid or	DNA-binding, Bromodomain,	3389	7357
  		mixed-lineage	Nuclear protein, Zinc-finger, Metal-
  		leukemia 4	binding, Transcription regulation,
  			Alternative splicing, Repeat
  NM_014729	TOX	thymus high mobility	Hypothetical protein	3390	7358
  		group box protein
  		TOX
  NM_014732	KIAA0513	KIAA0513 gene	Hypothetical protein	3391	7359
  		product
  NM_014735	KIAA0215	PHD finger protein	Zinc-finger	3392	7360
  		16
  NM_014737	RASSF2	Ras association	Hypothetical protein	3393	7361
  		(RaIGDS/AF-6)
  		domain family 2
  NM_014739	BTF	Bcl-2-associated	Hypothetical protein	3394	7362
  		transcription factor
  NM_014740	KIAA0111	DEAD (Asp-Glu-Ala-	ATP-binding, RNA-binding, DNA-	3395	7363
  		Asp) box polypeptide	binding, Helicase, Nuclear protein,
  		48	rRNA processing
  NM_014750	DLG7	discs, large homolog	Hypothetical protein	3396	7364
  		7 (Drosophila)
  NM_014751	MTSS1	metastasis	Cytoskeleton, Actin-binding, Coiled	3397	7365
  		suppressor 1	coil, Anti-oncogene, Alternative
  			splicing
  NM_014753	KIAA0187	BMS1-like, ribosome	Ribosome biogenesis, Nuclear	3398	7366
  		assembly protein	protein, ATP-binding
  		(yeast)
  NM_014763	MRPL19	mitochondrial	Ribosomal protein, Mitochondrion,	3399	7367
  		ribosomal protein	Transit peptide
  		L19
  NM_014764	DAZAP2	DAZ associated	Hypothetical protein	3400	7368
  		protein 2
  NM_014765	TOMM20-	translocase of outer	Transport, Protein transport, Outer	3401	7369
  	PENDING	mitochondrial	membrane, Mitochondrion,
  		membrane 20	Transmembrane
  		homolog (yeast)
  NM_014767	SPOCK2	sparc/osteonectin,	Extracellular matrix, Proteoglycan,	3402	7370
  		cwcv and kazal-like	Heparan sulfate, Glycoprotein,
  		domains	Calcium-binding, Signal
  		proteoglycan
  		(testican) 2
  NM_014776	GIT2	G protein-coupled	GTPase activation, Repeat, ANK	3403	7371
  		receptor kinase-	repeat, Zinc-finger,Alternative
  		interactor
  2	splicing, Hypothetical protein
  NM_014792	KIAA0125	KIAA0125	Hypothetical protein	3404	7372
  NM_014807	KIAA0285	KIAA0285 gene	Hypothetical protein	3405	7373
  		product
  NM_014808	FARP2	FERM, RhoGEF and	Hypothetical protein	3406	7374
  		pleckstrin domain
  		protein
  2
  NM_014815	TRAP100	thyroid hormone	Transcription regulation, Zinc-finger,	3407	7375
  		receptor-associated	Repeat, ATP-binding, Nuclear
  		protein (100 kDa)	protein
  NM_014820	TOMM70A	translocase of outer	Mitochondrion, Outer membrane,	3408	7376
  		mitochondrial	Transmembrane, Repeat,TPR
  		membrane
  70	repeat
  		homolog A (yeast)
  NM_014830	KIAA0352	KIAA0352 gene	Hypothetical protein, Transcription	3409	7377
  		product	regulation, DNA-binding, Zinc-finger,
  			Metal-binding, Nuclear protein,
  			Repeat
  NM_014835	OSBPL2	oxysterol binding	Lipid transport, Transport,	3410	7378
  		protein-like 2	Alternative splicing
  NM_014838	ZBED4	zinc finger, BED	Repeat, Zinc-finger	3411	7379
  		domain containing 4
  NM_014844	KIAA0329	KIAA0329	Hypothetical protein	3412	7380
  NM_014846	KIAA0196	KIAA0196 gene	Hypothetical protein	3413	7381
  		product
  NM_014861	KIAA0703	KIAA0703 gene	Hydrolase, Calcium transport,	3414	7382
  		product	Transmembrane, Phosphorylation,
  			ATP-binding, Metal-binding,
  			Magnesium, Calcium-binding,
  			Multigene family
  NM_014863	GALNAC4S-	B cell RAG	Hypothetical protein, Transferase	3415	7383
  	6ST	associated protein
  NM_014865	CNAP1	chromosome	DNA condensation, Mitosis, Cell	3416	7384
  		condensation-related	cycle, Nuclear protein,
  		SMC-associated	Phosphorylation
  		protein
  1
  NM_014869	KIAA0763	KIAA0763 gene	Hypothetical protein	3417	7385
  		product
  NM_014872	KIAA0354	zinc finger and BTB	Hypothetical protein, Metal-binding,	3418	7386
  		domain containing 5	Zinc, Zinc-finger
  NM_014873	KIAA0205	KIAA0205 gene	Hypothetical protein, Phospholipid	3419	7387
  		product	biosynthesis, Transferase,
  			Acyltransferase, Transmembrane
  NM_014874	MFN2	mitofusin 2	Hypothetical protein	3420	7388
  NM_014878	KIAA0020	minor	Hypothetical protein, RNA-binding,	3421	7389
  		histocompatibility	Repeat, Nuclear protein
  		antigen HA-8
  NM_014882	KIAA0053	KIAA0053 gene	Hypothetical protein	3422	7390
  		product
  NM_014886	YR-29	TGF beta-inducible	Nuclear protein	3423	7391
  		nuclear protein 1
  NM_014888	FAM3C	family with sequence	Signal	3424	7392
  		similarity 3, member C
  NM_014889	PITRM1	pitrilysin	Metalloprotease, Protease,	3425	7393
  		metalloproteinase 1	Hypothetical protein
  NM_014897	KIAA0924	KIAA0924 protein	Hypothetical protein, Metal-binding,	3426	7394
  			Nuclear protein, Zinc, Zinc-finger
  NM_014899	RHOBTB3	Rho-related BTB	Repeat	3427	7395
  		domain containing 3
  NM_014902	KIAA0964	disks large-	Membrane, Alternative splicing	3428	7396
  		associatedprotein 4
  NM_014907	KIAA0967	KIAA0967 protein	Hypothetical protein	3429	7397
  NM_014913	KIAA0863	KIAA0863 protein	Hypothetical protein, Metal-binding,	3430	7398
  			Zinc, Zinc-finger
  NM_014915	KIAA1074	KIAA1074 protein	ANK repeat, Repeat, Hypothetical	3431	7399
  			protein
  NM_014929	KIAA0971	KIAA0971 protein	Hypothetical protein	3432	7400
  NM_014931	KIAA1115	KIAA1115 protein	Hypothetical protein	3433	7401
  NM_014937	SAC2	inositol	Hypothetical protein	3434	7402
  		polyphosphate-5-
  		phosphatase F
  NM_014940	KIAA0872	HSV-1 stimulation-	Hypothetical protein	3435	7403
  		related gene 1
  NM_014944	CLSTN1	calsyntenin 1	Cell adhesion, Glycoprotein,	3436	7404
  			Transmembrane, Calcium-binding,
  			Repeat, Signal
  NM_014947	KIAA1041	KIAA1041 protein	Hypothetical protein, Transcription	3437	7405
  			regulation, DNA-binding, Nuclear
  			protein
  NM_014949	KIAA0907	KIAA0907 protein	Hypothetical protein	3438	7406
  NM_014953	DIS3	mitotic control	Exosome, Hydrolase, Nuclease,	3439	7407
  		protein dis3 homolog	Exonuclease, rRNA processing,
  			Nuclear protein, RNA-binding,
  			Hypothetical protein
  NM_014965	KIAA1042	OGT(O-Glc-NAc	Glycoprotein, Coiled coil,	3440	7408
  		transferase)-	Hypothetical protein
  		interacting protein
  		106 KDa
  NM_014966	DDX30	DEAH (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	3441	7409
  		His) box polypeptide	Hypothetical protein
  		30
  NM_014967	KIAA1018	KIAA1018 protein	Hypothetical protein	3442	7410
  NM_014977	ACINUS	apoptotic chromatin	Apoptosis, Nuclear protein,	3443	7411
  		condensation	Alternative splicing
  		inducer in the
  		nucleus
  NM_015057	KIAA0916	protein associated	Hypothetical protein	3444	7412
  		with Myc
  NM_015156	RCOR	REST corepressor	DNA-binding, Nuclear protein,	3445	7413
  			Hypothetical protein
  NM_015239	AGTPBP1	ATP/GTP binding	Hypothetical protein	3446	7414
  		protein 1
  NM_015310	EFA6R	ADP-ribosylation	Hypothetical protein, Guanine-	3447	7415
  		factor guanine	nucleotide releasingfactor
  		nucleotide factor
  6
  NM_015361	R3HDM	R3H domain (binds	Hypothetical protein	3448	7416
  		single-stranded
  		nucleic acids)
  		containing
  NM_015368	PANX1	pannexin	1	Gap junction, Transmembrane,	3449	7417
  			Polymorphism
  NM_015379	BRI3	brain protein I3	Transmembrane	3450	7418
  NM_015383	DJ328E19.C1.1	hypothetical protein	Hypothetical protein	3451	7419
  		DJ328E19.C1.1
  NM_015392	NPDC1	neural proliferation,	Hypothetical protein, Signal,	3452	7420
  		differentiation and	Transmembrane
  		control, 1
  NM_015400	DKFZP586N0721	DKFZP586N0721	Hypothetical protein	3453	7421
  		protein
  NM_015420	DKFZP564O0463	DKFZP564O0463	Repeat, WD repeat, Mitochondrion,	3454	7422
  		protein	Inner membrane, Transmembrane,
  			Transport, Hypothetical protein
  NM_015462	DKFZP586L0724	DKFZP586L0724	Hypothetical protein	3455	7423
  		protein
  NM_015492	DKFZP434H132	DKFZP434H132	Hypothetical protein	3456	7424
  		protein
  NM_015515	KRT23	keratin 23 (histone	Hypothetical protein, Intermediate	3457	7425
  		deacetylase	filament, Coiled coil, Keratin
  		inducible)
  NM_015524	C6orf4	chromosome 6 open	Alternative splicing	3458	7426
  		reading frame 4
  NM_015527	DKFZP434P1750	DKFZP434P1750	Hypothetical protein	3459	7427
  		protein
  NM_015530	GORASP2	golgi reassembly	Hypothetical protein	3460	7428
  		stacking protein 2,
  		55 kDa
  NM_015556	KIAA0440	signal-induced	Hypothetical protein	3461	7429
  		proliferation-
  		associated 1 like 1
  NM_015599	PGM3	phosphoglucomutase 3	Hypothetical protein, Isomerase,	3462	7430
  			Phosphorylation, Polymorphism
  NM_015610	DKFZP434J154	DKFZP434J154	Repeat, WD repeat, Hypothetical	3463	7431
  		protein	protein
  NM_015629	PRPF31	TCF3 (E2A) fusion	Hypothetical protein	3464	7432
  		partner (in childhood
  		Leukemia)
  NM_015640	PAI-RBP1	PAI-1 mRNA-binding	Hypothetical protein	3465	7433
  		protein
  NM_015644	ARPC4	actin related protein	Cytoskeleton, Hypothetical protein,	3466	7434
  		2/3 complex, subunit	Ligase
  		4, 20 kDa
  NM_015654	DKFZP564C103	DKFZP564C103	Hypothetical protein	3467	7435
  		protein
  NM_015684	ATP5S	ATP synthase, H+	Hydrogen ion transport, CF(0),	3468	7436
  		transporting,	Mitochondrion, Transit peptide,
  		mitochondrial F0	Hypothetical protein
  		complex, subunit s
  		(factor B)
  NM_015696	CL683	glutathione	Hypothetical protein,	3469	7437
  		peroxidase 6	Oxidoreductase, Peroxidase, Signal
  NM_015699	DJ159A19.3	hypothetical protein	Hypothetical protein	3470	7438
  		DJ159A19.3
  NM_015711	GLTSCR1	glioma tumor		3471	7439
  		suppressor
  		candidate region
  		gene
  1
  NM_015722	CALCYON	calcyon protein	Transmembrane, Glycoprotein	3472	7440
  NM_015836	WARS2	tryptophanyl tRNA	Aminoacyl-tRNA synthetase, Protein	3473	7441
  		synthetase 2	biosynthesis, Ligase, ATP-binding,
  		(mitochondrial)	Mitochondrion, Transit peptide
  NM_015838	FCN2	ficolin	Lectin, Collagen, Repeat,	3474	7442
  		(collagen/fibrinogen	Glycoprotein, Signal, Multigene
  		domain containing	family
  		lectin) 2 (hucolin)
  NM_015839	FCN2	ficolin	Lectin, Collagen, Repeat,	3475	7443
  		(collagen/fibrinogen	Glycoprotein, Signal, Multigene
  		domain containing	family
  		lectin) 2 (hucolin)
  NM_015853	LOC51035	ORF	Hypothetical protein	3476	7444
  NM_015855	WIT-1	Wilms tumor	Polymorphism	3477	7445
  		associated protein
  NM_015868	KIR2DL3	killer cell	Receptor, Immunoglobulin domain,	3478	7446
  		immunoglobulin-like	Glycoprotein, Signal,
  		receptor, two	Transmembrane, Repeat, Multigene
  		domains, long	family, Polymorphism, 3D-structure,
  		cytoplasmic tail, 3	Alternative splicing
  NM_015872	ZFP67	zinc finger protein 67	Metal-binding, Zinc, Zinc-finger	3479	7447
  		homolog (mouse)
  NM_015905	TIF1	transcriptional	Elongation factor, Protein	3480	7448
  		intermediary factor 1	biosynthesis, GTP-binding,
  			Methylation, Multigene family,
  			Transcription regulation, Repressor,
  			DNA-binding, Bromodomain, Zinc-
  			finger, Alternative splicing, Nuclear
  			protein, Coiled coil, Repeat
  NM_015907	LAP3	leucine	Hydrolase, Aminopeptidase,	3481	7449
  		aminopeptidase 3	Acetylation, Zinc, Magnesium,
  			Manganese
  NM_015908	ARS2	arsenate resistance	Hypothetical protein, Alternative	3482	7450
  		protein ARS2	splicing
  NM_015932	C13orf12	chromosome 13	Hypothetical protein	3483	7451
  		open reading frame
  		12
  NM_015942	LOC51001	CGI-12 protein	Hypothetical protein	3484	7452
  NM_015945	OVCOV1	solute carrier family	Hypothetical protein	3485	7453
  		35, member C2
  NM_015956	MRPL4	mitochondrial	Ribosomal protein	3486	7454
  		ribosomal protein L4
  NM_015958	LOC51611	CGI-30 protein	Transferase, Methyltransferase,	3487	7455
  			Alternative splicing, Hypothetical
  			protein
  NM_015959	LOC51075	thioredoxin-related	Hypothetical protein	3488	7456
  		transmembrane
  		protein
  2
  NM_015963	LOC51078	THAP domain	Zinc-finger, DNA-binding	3489	7457
  		containing 4
  NM_015967	PTPN22	protein tyrosine	Hydrolase, Alternative splicing,	3490	7458
  		phosphatase, non-	Hypothetical protein
  		receptor type 22
  		(lymphoid)
  NM_015971	MRPS7	mitochondrial	Ribosomal protein	3491	7459
  		ribosomal protein S7
  NM_015984	UCHL5	ubiquitin carboxyl-	Hypothetical protein, Ubl conjugation	3492	7460
  		terminal hydrolase	pathway, Hydrolase, Thiol protease,
  		L5	Proteasome, Alternative splicing,
  			Polymorphism
  NM_015999	LOC51094	adiponectin receptor 1	Fatty acid metabolism, Lipid	3493	7461
  			metabolism, Receptor,
  			Transmembrane
  NM_016006	CGI-58	abhydrolase domain	Hypothetical protein	3494	7462
  		containing 5
  NM_016017	UCHL5	ubiquitin carboxyl-	Hypothetical protein, Hydrolase, Ubl	3495	7463
  		terminal hydrolase	conjugation pathway, Thiol protease,
  		L5	Proteasome, Alternative splicing,
  			Polymorphism
  NM_016022	LOC51107	likely ortholog ofC. elegans	Transmembrane, Golgi stack,	3496	7464
  		anterior	Endoplasmic reticulum, Alternative
  		pharynx defective 1A	splicing
  NM_016026	RDH11	retinol	Oxidoreductase, NADP, Signal-	3497	7465
  		dehydrogenase 11	anchor, Transmembrane,
  		(all-trans and 9-cis)	Endoplasmic reticulum, Alternative
  			splicing
  NM_016039	LOC51637	chromosome 14	Hypothetical protein	3498	7466
  		open reading frame
  		166
  NM_016045	C20orf45	chromosome 20		3499	7467
  		open reading frame
  		45
  NM_016052	LOC51018	CGI-115 protein		3500	7468
  NM_016055	MRPL48	mitochondrial	Ribosomal protein, Mitochondrion	3501	7469
  		ribosomal protein
  		L48
  NM_016056	LOC51643	CGI-119 protein	Transmembrane, Polymorphism	3502	7470
  NM_016058	LOC51002	CGI-121 protein		3503	7471
  NM_016064	PILB	methionine sulfoxide	Hypothetical protein	3504	7472
  		reductase B
  NM_016072	LOC51026	CGI-141 protein	Hypothetical protein,	3505	7473
  			Transmembrane
  NM_016075	C13orf9	chromosome 13	Hypothetical protein	3506	7474
  		open reading frame 9
  NM_016082	CDK5RAP1	CDK5 regulatory	Alternative splicing	3507	7475
  		subunit associated
  		protein 1
  NM_016093	RPL26L1	ribosomal protein	Ribosomal protein	3508	7476
  		L26-like 1
  NM_016096	LOC51123	HSPC038 protein	Metal-binding, Zinc, Zinc-finger	3509	7477
  NM_016101	HSPC031	comparative gene	Hypothetical protein	3510	7478
  		identification
  		transcript 37
  NM_016120	RNF12	ring finger protein 12	Hypothetical protein, Metal-binding,	3511	7479
  			Zinc, Zinc-finger, Transcription
  			regulation
  NM_016122	LOC51134	NY-REN-58 antigen		3512	7480
  NM_016126	LOC51668	HSPCO34 protein		3513	7481
  NM_016127	MGC8721	hypothetical protein	Hypothetical protein	3514	7482
  		MGC8721
  NM_016129	COPS4	COP9 constitutive	Hypothetical protein	3515	7483
  		photomorphogenic
  		homolog subunit 4
  		(Arabidopsis)
  NM_016143	NSFL1C	NSFL1 (p97)	Hypothetical protein	3516	7484
  		cofactor (p47)
  NM_016167	RANBP9	retinoic acid	Hypothetical protein	3517	7485
  		repressible protein
  NM_016175	SQSTM1	truncated calcium	Hypothetical protein	3518	7486
  		binding protein
  NM_016183	C1orf33	chromosome 1 open	Hypothetical protein, Ribosomal	3519	7487
  		reading frame 33	protein
  NM_016184	CLECSF6	C-type (calcium	Receptor, Lectin	3520	7488
  		dependent,
  		carbohydrate-
  		recognition domain)
  		lectin,superfamily
  		member
  6
  NM_016187	BIN2	bridging integrator	2	Hypothetical protein	3521	7489
  NM_016194	GNB5	guanine nucleotide	Repeat, WD repeat, Transducer,	3522	7490
  		binding protein (G	Alternative splicing, Multigene family,
  		protein),beta 5	Hypothetical protein
  NM_016199	LSM7	LSM7 homolog, U6	Nuclear protein, Ribonucleoprotein,	3523	7491
  		small nuclear RNA	mRNA splicing, mRNA processing,
  		associated (S. cerevisiae)	RNA-binding
  NM_016202	LOC51157	LDL induced EC	Metal-binding, Zinc, Zinc-finger	3524	7492
  		protein
  NM_016207	CPSF3	cleavage and	mRNA processing, Nuclear protein,	3525	7493
  		polyadenylation	RNA-binding
  		specific factor 3,
  		73 kDa
  NM_016208	VPS28	vacuolar protein	Transport, Protein transport	3526	7494
  		sorting 28 (yeast)
  NM_016214	COL18A1	collagen, type XVIII,	Collagen, Extracellular matrix,	3527	7495
  		alpha 1	Connective tissue, Repeat,
  			Hydroxylation, Cell adhesion,
  			Glycoprotein, Signal, Alternative
  			splicing, Polymorphism, 3D-structure
  NM_016221	DCTN4	dynactin 4 (p62)	Hypothetical protein	3528	7496
  NM_016229	LOC51700	cytochrome b5	Hypothetical protein	3529	7497
  		reductase b5R.2
  NM_016237	ANAPC5	anaphase promoting	Ubl conjugation pathway, Cell cycle,	3530	7498
  		complex subunit 5	Cell division, Mitosis, Repeat, TPR
  			repeat, Alternative splicing
  NM_016258	HGRG8	high-glucose-		3531	7499
  		regulatedprotein 8
  NM_016271	RNF138	ring finger protein	Hypothetical protein, Metal-binding,	3532	7500
  		138	Zinc, Zinc-finger
  NM_016274	CKIP-1	CK2 interacting	Hypothetical protein	3533	7501
  		protein 1; HQ0024c
  		protein
  NM_016283	TAF9	TAF9 RNA	ATP-binding, Transcription	3534	7502
  		polymerase II, TATA	regulation, Nuclear protein,
  		box binding protein	Polymorphism, Hypothetical protein,
  		(TBP)-associated	Cell cycle
  		factor, 32 kDa
  NM_016293	BIN2	bridging integrator	2	Hypothetical protein	3535	7503
  NM_016299	HSP70-4	likely ortholog of	ATP-binding	3536	7504
  		mouse heat shock
  		protein, 70kDa 4
  NM_016304	C15orf15	chromosome 15	Ribosomal protein	3537	7505
  		open reading frame
  		15
  NM_016306	DNAJB11	DnaJ (Hsp40)	Chaperone, Endoplasmic reticulum,	3538	7506
  		homolog, subfamily	Signal, Polymorphism
  		B, member 11
  NM_016309	LCMT1	leucine carboxyl	Hypothetical protein,	3539	7507
  		methyltransferase 1	Methyltransferase, Transferase
  NM_016312	WBP11	WW domain binding	Hypothetical protein	3540	7508
  		protein 11
  NM_016316	REV1L	REV1-like (yeast)	Transferase, Integrin, Hypothetical	3541	7509
  			protein
  NM_016326	CKLF	chemokine-like	Chemotaxis, Cytokine,	3542	7510
  		factor	Transmembrane, Alternative splicing
  NM_016327	UPB1	ureidopropionase,	Hydrolase, Allosteric enzyme, Zinc	3543	7511
  		beta
  NM_016331	LOC51193	zinc finger protein	Metal-binding, Zinc, Zinc-finger	3544	7512
  		ANC_2H01
  NM_016332	SEPX1	selenoprotein X, 1	Oxidoreductase, Metal-binding, Zinc,	3545	7513
  			Selenium, Selenocysteine
  NM_016333	SRRM2	serine/arginine	Hypothetical protein	3546	7514
  		repetitive matrix 2
  NM_016334	SH120	putative G-protein	Receptor	3547	7515
  		coupled receptor
  NM_016354	SLC21A12	solute carrier organic	Transmembrane, Transport, Ion	3548	7516
  		anion transporter	transport, Glycoprotein, Alternative
  		family, member 4A1	splicing
  NM_016355	LOC51202	DEAD (Asp-Glu-Ala-	ATP-binding, Helicase, Hydrolase,	3549	7517
  		Asp) box polypeptide	Hypothetical protein
  		47
  NM_016362	GHRL	ghrelin precursor	Hormone, Cleavage on pair of basic	3550	7518
  			residues, Signal, Lipoprotein,
  			Alternative splicing
  NM_016364	DUSP13	dual specificity	Hydrolase	3551	7519
  		phosphatase 13
  NM_016373	WWOX	WW domain	Oxidoreductase	3552	7520
  		containing
  		oxidoreductase
  NM_016377	AKAP7	A kinase (PRKA)	Membrane, Myristate, Palmitate,	3553	7521
  		anchor protein 7	Lipoprotein, Alternative splicing
  NM_016381	TREX1	three prime repair	Exonuclease, Hypothetical protein	3554	7522
  		exonuclease 1
  NM_016385	CYLD	cylindromatosis	Hypothetical protein	3555	7523
  		(turban tumor
  		syndrome)
  NM_016387	HSPC060	hypothetical protein		3556	7524
  		HSPC060
  NM_016391	HSPC111	hypothetical protein	Hypothetical protein, Nuclear protein	3557	7525
  		HSPC111
  NM_016397	TH1L	TH1-like	Transcription regulation, Repressor,	3558	7526
  		(Drosophila)	Nuclear protein, Alternative splicing,
  			Alternative initiation
  NM_016399	HSPC132	hypothetical protein	Hypothetical protein	3559	7527
  		HSPC132
  NM_016403	HSPC148	hypothetical protein	Hypothetical protein	3560	7528
  		HSPC148
  NM_016407	C20orf43	chromosome 20	Alternative splicing	3561	7529
  		open reading frame
  		43
  NM_016418	NF2	neurofibromin 2	Structural protein, Cytoskeleton,	3562	7530
  		(bilateral acoustic	Anti-oncogene, Disease mutation,
  		neuroma)	Alternative splicing, Deafness, 3D-
  			structure
  NM_016424	LUC7A	cisplatin resistance-	Phosphorylation, Hypothetical	3563	7531
  		associated	protein
  		overexpressed
  		protein
  NM_016431	MAPK8IP2	mitogen-activated	SH3 domain, Alternative splicing	3564	7532
  		protein kinase 8
  		interactingprotein 2
  NM_016441	CRIM1	cysteine-rich motor	Signal	3565	7533
  		neuron 1
  NM_016463	HSPC195	hypothetical protein	Hypothetical protein	3566	7534
  		HSPC195
  NM_016465	LOC51238	blocked early in	Hypothetical protein	3567	7535
  		transport 1 homolog
  		(S. cerevisiae) like
  NM_016468	C14orf112	chromosome 14	Hypothetical protein	3568	7536
  		open reading frame
  		112
  NM_016477	FOXP1	forkhead box P1	Hypothetical protein, Transcription	3569	7537
  			regulation, DNA-binding, Zinc-finger,
  			Metal-binding, Nuclear protein,
  			Alternative splicing
  NM_016479	SCOTIN	scotin	Hypothetical protein	3570	7538
  NM_016501	FLJ10597	hypothetical protein	Hypothetical protein	3571	7539
  		FLJ10597
  NM_016503	MRPL30	mitochondrial	Hypothetical protein	3572	7540
  		ribosomal protein
  		L30
  NM_016507	CRK7	CDC2-related	Transferase, Serine/threonine-	3573	7541
  		protein kinase 7	protein kinase, ATP-binding, Nuclear
  			protein
  NM_016524	LOC51760	B/K protein	Hypothetical protein	3574	7542
  NM_016533	NINJ2	ninjurin 2	Cell adhesion, Transmembrane	3575	7543
  NM_016538	SIRT7	sirtuin (silent mating	Hydrolase, NAD, Metal-binding,	3576	7544
  		type information	Zinc,Alternative splicing
  		regulation
  2
  		homolog) 7 (S. cerevisiae)
  NM_016565	E2IG2	E2IG2 protein		3577	7545
  NM_016567	BCCIP	BRCA2 and	Helicase, Hypothetical protein	3578	7546
  		CDKN1A interacting
  		protein
  NM_016572	USP21	ubiquitin specific	Hypothetical protein, Ubl conjugation	3579	7547
  		protease 21	pathway, Hydrolase, Thiol protease,
  			Multigene family
  NM_016573	LOC51291	Gem-interacting		3580	7548
  		protein
  NM_016574	DRD2	dopamine receptor	G-protein coupled receptor,	3581	7549
  		D2	Transmembrane, Glycoprotein,
  			Multigene family, Alternative splicing,
  			Disease mutation, Polymorphism,
  			3D-structure
  NM_016582	FLJ20539	solute carrier family	Hypothetical protein	3582	7550
  		15,member 3
  NM_016594	FKBP11	FK506 binding	Isomerase, Rotamase, Signal	3583	7551
  		protein 11, 19 kDa
  NM_016598	ZDHHC3	zinc finger, DHHC	Transmembrane, Golgi stack, Zinc-	3584	7552
  		domain containing 3	finger, Alternative splicing
  NM_016603	C5orf5	chromosome 5 open	GTPase activation	3585	7553
  		reading frame 5
  NM_016608	ALEX1	ALEX1 protein	Hypothetical protein	3586	7554
  NM_016610	TLR8	toll-like receptor 8	Hypothetical protein, Receptor,	3587	7555
  			Immune response, Inflammatory
  			response, Signal, Transmembrane,
  			Repeat, Leucine-rich repeat,
  			Glycoprotein
  NM_016612	MSCP	mitochondrial solute	Hypothetical protein	3588	7556
  		carrier protein
  NM_016616	TXNDC3	thioredoxin domain	Redox-active center	3589	7557
  		containing 3
  		(spermatozoa)
  NM_016619	PLAC8	placenta-specific 8		3590	7558
  NM_016623	BM-009	hypothetical protein	Hypothetical protein	3591	7559
  		BM-009
  NM_016626	LOC51320	hypothetical protein	Metal-binding, Zinc, Zinc-finger	3592	7560
  		LOC51320
  NM_016630	ACP33	acid cluster protein	Hypothetical protein	3593	7561
  		33
  NM_016639	TNFRSF12A	tumor necrosis factor	Receptor, Angiogenesis, Apoptosis,	3594	7562
  		receptor superfamily,	Transmembrane, Signal, Alternative
  		member 12A	splicing
  NM_016640	MRPS30	mitochondrial	Ribosomal protein, Mitochondrion	3595	7563
  		ribosomal protein
  		S30
  NM_016733	LIMK2	LIMdomain kinase 2	Transferase, Serine/threonine-	3596	7564
  			protein kinase, ATP-binding, Repeat,
  			LIM domain, Metal-binding, Zinc,
  			Kinase, Tyrosine-protein kinase,
  			Hypothetical protein
  NM_016826	OGG1	8-oxoguanine DNA	Hydrolase, Nuclease, Endonuclease,	3597	7565
  		glycosylase	Lyase, DNA repair, Glycosidase,
  			Multifunctional enzyme, Nuclear
  			protein, Mitochondrion, Alternative
  			splicing, Polymorphism, 3D-
  			structure, Transferase,
  			Serine/threonine-protein kinase,
  			Calmodulin-binding,
  			Phosphorylation,
  NM_016827	OGG1	8-oxoguanine DNA	Hydrolase, Nuclease, Endonuclease,	3598	7566
  		glycosylase	Lyase, DNA repair, Glycosidase,
  			Multifunctional enzyme, Nuclear
  			protein, Mitochondrion, Alternative
  			splicing, Polymorphism, 3D-
  			structure, Transferase,
  			Serine/threonine-protein kinase,
  			Calmodulin-binding,
  			Phosphorylation,
  NM_016836	RBMS1	RNA binding motif,	DNA-binding, DNA replication, RNA-	3599	7567
  		single stranded	binding, Nuclear protein,
  		interactingprotein 1	Phosphorylation
  NM_016839	RBMS1	RNA binding motif,	DNA-binding, DNA replication, RNA-	3600	7568
  		single stranded	binding, Nuclear protein,
  		interactingprotein 1	Phosphorylation
  NM_016936	UBN1	ubinuclein 1		3601	7569
  NM_016951	CKLF	chemokine-like	Chemotaxis, Cytokine,	3602	7570
  		factor	Transmembrane, Alternative splicing
  NM_017409	HOXC10	homeo box C10	Homeobox, DNA-binding,	3603	7571
  			Developmental protein, Nuclear
  			protein, Transcription regulation
  NM_017414	USP18	ubiquitin specific	Ubl conjugation pathway, Hydrolase,	3604	7572
  		protease 18	Thiol protease, Multigene family
  NM_017415	KLHL3	kelch-like 3	Cytoskeleton, Actin-binding, Kelch	3605	7573
  		(Drosophila)	repeat, Repeat, Alternative splicing
  NM_017421	COQ3	coenzyme Q3	Transferase	3606	7574
  		homolog,
  		methyltransferase
  		(yeast)
  NM_017424	CECR1	cat eye syndrome	Hydrolase, Signal, Hypothetical	3607	7575
  		chromosome region,	protein
  		candidate
  1
  NM_017426	NUP54	nucleoporin 54 kDa	Hypothetical protein, Transport,	3608	7576
  			Nuclear protein, Repeat,
  			Glycoprotein, Alternative splicing
  NM_017451	BAIAP2	BAI1-associated	Receptor, SH3 domain, Hypothetical	3609	7577
  		protein 2	protein, ATP-binding, Transferase
  NM_017455	SDFR1	stromal cell derived	Immunoglobulin domain,	3610	7578
  		factor receptor 1	Hypothetical protein, Receptor
  NM_017456	PSCD1	pleckstrin homology,	Guanine-nucleotide releasing factor,	3611	7579
  		Sec7 and coiled-coil	Coiled coil, Alternative splicing, 3D-
  		domains 1(cytohesin	structure
  		1)
  NM_017491	WDR1	WD repeat domain 1	Repeat, WD repeat, Hypothetical	3612	7580
  			protein, Actin-binding, Cytoskeleton,
  			Alternative splicing, Polymorphism
  NM_017493	HSHIN1	HIV-1 induced		3613	7581
  		protein HIN-1
  NM_017535	DKFZp566H0824	hypothetical protein	Hypothetical protein	3614	7582
  		DKFZp566H0824
  NM_017544	NRF	NF-kappa B-	Transcription regulation, Repressor,	3615	7583
  		repressing factor	DNA-binding, Nuclear protein
  NM_017546	C40	hypothetical protein	Hypothetical protein	3616	7584
  		C40
  NM_017555	EGLN2	egl ninehomolog 2	Oxidoreductase, Dioxygenase,	3617	7585
  		(C. elegans)	Nuclear protein, Iron, Vitamin C
  NM_017567	NAGK	N-acetylglucosamine	Kinase, Transferase, ATP-binding,	3618	7586
  		kinase	Phosphorylation, Hypothetical
  			protein
  NM_017571	LOC55580	hypothetical protein	Hypothetical protein	3619	7587
  		LOC55580
  NM_017572	MKNK2	MAP kinase-	Hypothetical protein, ATP-binding,	3620	7588
  		interacting	Kinase, Serine/threonine-protein
  		serine/threonine	kinase, Transferase,Translation
  		kinase
  2	regulation, Phosphorylation,
  			Alternative splicing
  NM_017596	KIAA0449	KIAA0449 protein	Hypothetical protein, Repeat, WD	3621	7589
  			repeat
  NM_017622	FLJ20014	hypothetical protein	Hypothetical protein	3622	7590
  		FLJ20014
  NM_017631	FLJ20035	hypothetical protein	Hypothetical protein	3623	7591
  		FLJ20035
  NM_017633	C6orf37	chromosome 6 open	Hypothetical protein	3624	7592
  		reading frame 37
  NM_017646	IPT	tRNA	Hypothetical protein, Transferase	3625	7593
  		isopentenyltransferase 1
  NM_017664	ANKRD10	ankyrin repeat	Hypothetical protein, ANK repeat,	3626	7594
  		domain 10	Repeat
  NM_017681	FLJ20130	hypothetical protein	Hypothetical protein, Porin	3627	7595
  		FLJ20130
  NM_017694	FLJ20160	FLJ20160 protein	Hypothetical protein	3628	7596
  NM_017700	FLJ20184	hypothetical protein	Hypothetical protein	3629	7597
  		FLJ20184
  NM_017703	FBXL12	F-box and leucine-	Ubl conjugation pathway, Repeat,	3630	7598
  		rich repeat protein	Leucine-rich repeat, Alternative
  		12	splicing
  NM_017714	C20orf13	chromosome	20	Hydrolase	3631	7599
  		open reading frame
  		13
  NM_017730	FLJ20259	FLJ20259 protein	Hypothetical protein	3632	7600
  NM_017735	FLJ20272	hypothetical protein	Hypothetical protein	3633	7601
  		FLJ20272
  NM_017737	FLJ20275	transducer of Cdc42-	Hypothetical protein, SH3 domain	3634	7602
  		dependent actin
  		assembly
  1
  NM_017740	ZDHHC7	zinc finger, DHHC	Transmembrane, Zinc-finger,	3635	7603
  		domain containing 7	Alternative splicing
  NM_017742	FLJ20281	zinc finger, CCHC	Hypothetical protein, Zinc-finger	3636	7604
  		domain containing 2
  NM_017746	FLJ20287	hypothetical protein	Hypothetical protein	3637	7605
  		FLJ20287
  NM_017756	FLJ20306	hypothetical protein	Hypothetical protein	3638	7606
  		FLJ20306
  NM_017775	FLJ20343	hypothetical protein	Hypothetical protein	3639	7607
  		FLJ20343
  NM_017785	FLJ20364	hypothetical protein	Hypothetical protein	3640	7608
  		FLJ20364
  NM_017787	FLJ20154	chromosome 10	Hypothetical protein	3641	7609
  		open reading frame
  		26
  NM_017801	CKLFSF6	chemokine-like	Chemotaxis, Cytokine,	3642	7610
  		factorsuper family 6	Transmembrane
  NM_017803	FLJ20399	hypothetical protein	Hypothetical protein	3643	7611
  		FLJ20399
  NM_017812	FLJ20420	hypothetical protein	Hypothetical protein	3644	7612
  		FLJ20420
  NM_017814	FLJ20422	hypothetical protein	Hypothetical protein	3645	7613
  		FLJ20422
  NM_017816	LYAR	hypothetical protein	Hypothetical protein	3646	7614
  		FLJ20425
  NM_017817	RAB20	RAB20, member	GTP-binding, Lipoprotein,	3647	7615
  		RAS oncogene	Prenylation, Protein transport,
  		family	Polymorphism
  NM_017819	FLJ20432	hypothetical protein	Hypothetical protein	3648	7616
  		FLJ20432
  NM_017820	FLJ20433	hypothetical protein	Hypothetical protein	3649	7617
  		FLJ20433
  NM_017821	RHBDL2	rhomboid, veinlet-	Hydrolase, Protease, Serine	3650	7618
  		like 2 (Drosophila)	protease, Transmembrane
  NM_017824	FLJ20445	hypothetical protein	Hypothetical protein	3651	7619
  		FLJ20445
  NM_017836	FLJ20473	hypothetical protein	Hypothetical protein	3652	7620
  		FLJ20473
  NM_017838	NOLA2	nucleolar protein		3653	7621
  		family A, member 2
  		(H/ACA small
  		nucleolar RNPs)
  NM_017840	MRPL16	mitochondrial	Ribosomal protein, Hypothetical	3654	7622
  		ribosomal protein	protein
  		L16
  NM_017844	ANKMY1	ankyrin repeat and	Hypothetical protein, ANK repeat,	3655	7623
  		MYND domain	Repeat, Zinc-finger, Alternative
  		containing 1	splicing
  NM_017847	C1orf27	chromosome 1 open	Hypothetical protein	3656	7624
  		reading frame 27
  NM_017849	FLJ20507	hypothetical protein	Hypothetical protein	3657	7625
  		FLJ20507
  NM_017850	FLJ20508	hypothetical protein	Hypothetical protein	3658	7626
  		FLJ20508
  NM_017859	URKL1	uridine kinase-like 1	Transferase, Kinase, ATP-binding	3659	7627
  NM_017866	FLJ20533	hypothetical protein	Hypothetical protein	3660	7628
  		FLJ20533
  NM_017874	C20orf27	chromosome 20	Hypothetical protein	3661	7629
  		open reading frame
  		27
  NM_017885	FLJ20568	host cell factor C1	Hypothetical protein	3662	7630
  		regulator 1 (XPO1
  		dependant)
  NM_017895	DDX27	DEAD (Asp-Glu-Ala-	Hydrolase, Helicase, ATP-binding,	3663	7631
  		Asp) box polypeptide	Nuclear protein, Alternative splicing
  		27
  NM_017899	TSC	hypothetical protein	Calcium-binding, Hypothetical	3664	7632
  		FLJ20607	protein
  NM_017900	FLJ20608	aurora-A kinase	Hypothetical protein, Nuclear protein	3665	7633
  		interacting protein
  NM_017906	FLJ20624	PAK1 interacting	Hypothetical protein, Repeat, WD	3666	7634
  		protein 1	repeat
  NM_017907	FLJ20625	hypothetical protein	Hypothetical protein	3667	7635
  		FLJ20625
  NM_017910	FLJ20628	hypothetical protein	Hypothetical protein	3668	7636
  		FLJ20628
  NM_017942	BTBD1	BTB (POZ) domain		3669	7637
  		containing 1
  NM_017952	FLJ20758	FLJ20758 protein	Hypothetical protein	3670	7638
  NM_017953	FLJ20729	hypothetical protein	Hypothetical protein	3671	7639
  		FLJ20729
  NM_017956	FLJ20772	hypothetical protein	Hypothetical protein	3672	7640
  		FLJ20772
  NM_017983	KIAA1001	hypothetical protein	Hypothetical protein, Repeat, WD	3673	7641
  		FLJ10055	repeat
  NM_018007	FBXO4	Homo sapienscDNA	Ubl conjugation pathway,	3674	7642
  		FLJ10141 fis, clone	Hypothetical protein
  		HEMBA1003199.
  NM_018024	FLJ10204	hypothetical protein	Hypothetical protein	3675	7643
  		FLJ10204
  NM_018044	WBSCR20A	Williams Beuren	Nuclear protein, Transport,	3676	7644
  		syndrome	Transmembrane, Repeat,
  		chromosome region	Hypothetical protein
  		20A
  NM_018045	FLJ10276	hypothetical protein	Hypothetical protein	3677	7645
  		FLJ10276
  NM_018050	FLJ10298	hypothetical protein	Hypothetical protein	3678	7646
  		FLJ10298
  NM_018051	FLJ10300	hypothetical protein	Hypothetical protein, Repeat, WD	3679	7647
  		FLJ10300	repeat
  NM_018053	FLJ10307	hypothetical protein	Hypothetical protein	3680	7648
  		FLJ10307
  NM_018056	FLJ10315	hypothetical protein	Hypothetical protein	3681	7649
  		FLJ10315
  NM_018059	FLJ10324	hypothetical protein	Hypothetical protein	3682	7650
  		FLJ10324
  NM_018067	FLJ10350	hypothetical protein	Hypothetical protein	3683	7651
  		FLJ10350
  NM_018075	FLJ10375	hypothetical protein	Hypothetical protein	3684	7652
  		FLJ10375
  NM_018087	FLJ10407	hypothetical protein	Hypothetical protein	3685	7653
  		FLJ10407
  NM_018089	FLJ10415	hypothetical protein	Hypothetical protein, ANK repeat,	3686	7654
  		FLJ10415	Repeat
  NM_018093	FLJ10439	hypothetical protein	Hypothetical protein, Repeat, WD	3687	7655
  		FLJ10439	repeat
  NM_018099	FLJ10462	hypothetical protein	Hypothetical protein	3688	7656
  		FLJ10462
  NM_018100	FLJ10466	EF-hand domain (C-	Hypothetical protein	3689	7657
  		terminal) containing 1
  NM_018113	LIMR	lipocalin-interacting	Hypothetical protein, Receptor	3690	7658
  		membrane receptor
  NM_018119	SIN	RNA polymerase III	Transferase, DNA-directed RNA	3691	7659
  		80 kDa subunit	polymerase, Transcription, Nuclear
  		RPC5	protein, Alternative splicing
  NM_018125	FLJ10521	hypothetical protein	Hypothetical protein	3692	7660
  		FLJ10521
  NM_018127	ELAC2	elaC homolog 2 (E. coli)	Hypothetical protein	3693	7661
  NM_018128	SRR	hypothetical protein	Isomerase, Pyridoxal phosphate,	3694	7662
  		FLJ10534	Hypothetical protein
  NM_018137	PRMT6	protein arginine N-	Transferase, Methyltransferase,	3695	7663
  		methyltransferase 6	Nuclear protein, Methylation
  NM_018140	FLJ10565	hypothetical protein	Hypothetical protein	3696	7664
  		FLJ10565
  NM_018142	FLJ10569	hypothetical protein	Hypothetical protein	3697	7665
  		FLJ10569
  NM_018147	FAIM	Fas apoptotic	Apoptosis, Alternative splicing	3698	7666
  		inhibitory molecule
  NM_018158	SLC4A1AP	solute carrier family	Hypothetical protein, Transcription	3699	7667
  		4 (anion exchanger),	regulation, Nuclear protein, Antigen,
  		member 1, adaptor	Alternative splicing
  		protein
  NM_018161	FLJ10631	NAD synthetase 1	Hypothetical protein	3700	7668
  NM_018169	FLJ10652	hypothetical protein	Hypothetical protein	3701	7669
  		FLJ10652
  NM_018170	FLJ10656	hypothetical protein	Kinase, Hypothetical protein	3702	7670
  		FLJ10656
  NM_018174	VCY2IP1	VCY2 interacting	Hypothetical protein	3703	7671
  		protein 1
  NM_018182	FLJ10700	hypothetical protein	Hypothetical protein	3704	7672
  		FLJ10700
  NM_018191	RCBTB1	regulator of	Hypothetical protein	3705	7673
  		chromosome
  		condensation
  		(RCC1) and BTB
  		(POZ)domain
  		containing protein
  1
  NM_018194	FLJ10724	melanoma antigen	Hypothetical protein	3706	7674
  		recognized byT
  		cells
  2
  NM_018195	FLJ10726	hypothetical protein	Hypothetical protein	3707	7675
  		FLJ10726
  NM_018197	ZFP64	zinc finger protein 64	Transcription regulation, Zinc-finger,	3708	7676
  		homolog (mouse)	Metal-binding, Nuclear protein, DNA-
  			binding, Repeat, Alternative splicing
  NM_018203	FLJ10748	hypothetical protein	Hypothetical protein	3709	7677
  		FLJ10748
  NM_018208	FLJ10761	putative	Transferase, Kinase	3710	7678
  		ethanolamine kinase
  NM_018209	ARFGAP1	ADP-ribosylation	Transport, Protein transport,	3711	7679
  		factor GTPase	GTPase activation, Golgi stack,
  		activatingprotein 1	Zinc-finger, Alternative splicing,
  			Polymorphism
  NM_018217	C20orf31	chromosome 20	Hydrolase, Glycosidase,	3712	7680
  		open reading frame	Glycoprotein, Signal, Polymorphism
  		31
  NM_018226	RNPEPL1	arginyl	Aminopeptidase, Hydrolase, Zinc,	3713	7681
  		aminopeptidase	Metalloprotease
  		(aminopeptidase B)-
  		like 1
  NM_018235	FLJ10830	cytosolic nonspecific	Hydrolase, Carboxypeptidase,	3714	7682
  		dipeptidase (EC	Metalloprotease, Hypothetical
  		3.4.13.18)	protein
  NM_018243	FLJ10849	hypothetical protein	Hypothetical protein	3715	7683
  		FLJ10849
  NM_018246	FLJ10853	hypothetical protein	Hypothetical protein	3716	7684
  		FLJ10853
  NM_018255	STATIP1	signal transducer	Hypothetical protein, Repeat, WD	3717	7685
  		and activator of	repeat
  		transcription
  3
  		interactingprotein 1
  NM_018256	WDR12	WD repeat domain	Repeat, WD repeat, Polymorphism	3718	7686
  		12
  NM_018257	C20orf36	chromosome	20	Transcription regulation, Zinc-finger,	3719	7687
  		open reading frame	DNA-binding, Nuclear protein,
  		36	Repeat, Alternative splicing
  NM_018259	FLJ10890	hypothetical protein	Hypothetical protein	3720	7688
  		FLJ10890
  NM_018264	FLJ10900	hypothetical protein	Hypothetical protein	3721	7689
  		FLJ10900
  NM_018265	FLJ10901	hypothetical protein	Hypothetical protein	3722	7690
  		FLJ10901
  NM_018267	H2AFJ	H2A histone family,	Hypothetical protein	3723	7691
  		member J
  NM_018275	FLJ10925	hypothetical protein	Hypothetical protein	3724	7692
  		FLJ10925
  NM_018306	FLJ11036	hypothetical protein	Hypothetical protein	3725	7693
  		FLJ11036
  NM_018317	FLJ11082	hypothetical protein	Hypothetical protein	3726	7694
  		FLJ11082
  NM_018319	TDP1	tyrosyl-DNA	Hypothetical protein, Hydrolase,	3727	7695
  		phosphodiesterase 1	DNA repair, Repeat, Nuclear protein,
  			3D-structure, Disease mutation
  NM_018321	RAD1	BRIX	Hypothetical protein, Ribosome	3728	7696
  			biogenesis, Nuclear protein, Cell
  			cycle, Exonuclease
  NM_018322	C6orf64	chromosome 6 open	Hypothetical protein, Dynein	3729	7697
  		reading frame 64
  NM_018324	FLJ11106	hypothetical protein	Hypothetical protein	3730	7698
  		FLJ11106
  NM_018326	HIMAP4	immunity associated	GTP-binding, Coiled coil,	3731	7699
  		protein 4	Polymorphism
  NM_018332	DDX19	hypothetical protein	ATP-binding, Helicase, Hydrolase,	3732	7700
  		FLJ11126	RNA-binding, Nuclear protein,
  			Hypothetical protein
  NM_018333	FLJ20666	hypothetical protein	Hypothetical protein	3733	7701
  		FLJ20666
  NM_018358	FLJ11198	ATP-binding	Hypothetical protein, ATP-binding	3734	7702
  		cassette, sub-family
  		F (GCN20),member 3
  NM_018359	FLJ11200	hypothetical protein	Hypothetical protein	3735	7703
  		FLJ11200
  NM_018361	FLJ11210	acid acyltransferase-	Phospholipid biosynthesis,	3736	7704
  		epsilon	Transferase, Acyltransferase,
  			Transmembrane
  NM_018371	ChGn	chondroitin beta1,4	Transferase, Hypothetical protein	3737	7705
  		N-
  		acetylgalactosaminyl
  		transferase
  NM_018373	SYNJ2BP	synaptojanin	2	Mitochondrion, Outer membrane,	3738	7706
  		binding protein	Transmembrane
  NM_018379	FLJ11280	hypothetical protein	Hypothetical protein	3739	7707
  		FLJ11280
  NM_018386	FLJ11305	hypothetical protein	Hypothetical protein	3740	7708
  		FLJ11305
  NM_018387	STRBP	spermatid	Hypothetical protein	3741	7709
  		perinuclear RNA
  		binding protein
  NM_018391	FLJ23277	ubiquitin specific	Hypothetical protein, Protease	3742	7710
  		protease 31
  NM_018394	FLJ11342	hypothetical protein	Hypothetical protein	3743	7711
  		FLJ11342
  NM_018399	VNN3	vanin 3	Hydrolase, Signal, Glycoprotein,	3744	7712
  			GPI-anchor, Lipoprotein
  NM_018403	HSA275986	transcription factor	Hypothetical protein	3745	7713
  		SMIF
  NM_018404	CENTA2	centaurin,alpha 2	GTPase activation, Repeat, Zinc-	3746	7714
  			finger
  NM_018407	LAPTM4B	lysosomal		3747	7715
  		associatedprotein
  		transmembrane
  4
  		beta
  NM_018421	TBC1D2	TBC1 domain family,	Hypothetical protein, GTPase	3748	7716
  		member 2	activation, Antigen
  NM_018422	DKFZp761K1423	hypothetical protein	Hypothetical protein	3749	7717
  		DKFZp761K1423
  NM_018423	DKFZp761p1010	protein kinase	ATP-binding, Kinase, Receptor,	3750	7718
  		STYK1	Transferase, Tyrosine-protein
  			kinase, Hypothetical protein
  NM_018441	PECR	peroxisomal trans 2-	Oxidoreductase	3751	7719
  		enoyl CoA reductase
  NM_018443	ZNF302	zinc finger protein	Hypothetical protein, Metal-binding,	3752	7720
  		302	Zinc, Zinc-finger, Transcription
  			regulation, DNA-binding, Nuclear
  			protein, Repeat, Alternative splicing
  NM_018449	UBAP2	ubiquitin associated	Hypothetical protein	3753	7721
  		protein 2
  NM_018452	C6orf35	chromosome 6 open	Hypothetical protein	3754	7722
  		reading frame 35
  NM_018457	DKFZP564J157	DKFZp564J157	Hypothetical protein	3755	7723
  		protein
  NM_018465	MDS030	chromosome 9 open	Hypothetical protein	3756	7724
  		reading frame 46
  NM_018472	HT011	uncharacterized	Hypothetical protein	3757	7725
  		hypothalamus
  		protein HT011
  NM_018480	HT007	uncharacterized	Hypothetical protein	3758	7726
  		hypothalamus
  		protein HT007
  NM_018485	GPR77	G protein-coupled	G-protein coupled receptor,	3759	7727
  		receptor 77	Transmembrane, Glycoprotein
  NM_018486	HDAC8	histone deacetylase	8	Hydrolase, Nuclear protein,	3760	7728
  			Chromatin regulator, Transcription
  			regulation, Repressor, Alternative
  			splicing
  NM_018491	LOC55871	COBW-like protein	Hypothetical protein	3761	7729
  NM_018515	PRO2176	EST, Highly similar		3762	7730
  		to hypothetical
  		protein PRO2176
  		[Homo sapiens]
  		[H. sapiens]
  NM_018520	PRO2268	hypothetical protein		3763	7731
  		PRO2268
  NM_018533	RAB7	Homo sapienscDNA	GTP-binding, Lipoprotein,	3764	7732
  		FLJ20819 fis, clone	Prenylation, Protein transport,
  		ADSE00511.	Hypothetical protein
  NM_018556	SIRPB2	signal-regulatory	Repeat, Signal, Transmembrane,	3765	7733
  		protein beta 2	Immunoglobulin domain,
  			Glycoprotein, Alternative splicing
  NM_018569	PRO0971	hypothetical protein	Hypothetical protein	3766	7734
  		PRO0971
  NM_018572	PRO1051	E2F transcription		3767	7735
  		factor 3
  NM_018590	PRO0082	chondroitin sulfate	Hypothetical protein, Transferase	3768	7736
  		GalNAcT-2
  NM_018594	PRO0823	FYN binding protein	SH3 domain, Phosphorylation,	3769	7737
  		(FYB-120/130)	Nuclear protein, Coiled coil,
  			Alternative splicing
  NM_018615	PRO2032	Homo sapiens		3770	7738
  		hypothetical protein
  		PRO2032
  		(PRO2032), mRNA.
  NM_018638	EKI1	ethanolamine kinase	Transferase, Kinase	3771	7739
  NM_018643	TREM1	triggering receptor	Receptor	3772	7740
  		expressed on
  		myeloid cells 1
  NM_018648	NOLA3	nucleolar protein		3773	7741
  		family A, member 3
  		(H/ACA small
  		nucleolar RNPs)
  NM_018676	THSD1	thrombospondin,	Signal	3774	7742
  		type I,domain 1
  NM_018687	LOC55908	hepatocellular		3775	7743
  		carcinoma-
  		associated gene
  		TD26
  NM_018688	BIN3	bridging integrator	3	Septation, Cytoskeleton, Coiled coil,	3776	7744
  			Hypothetical protein
  NM_018690	APOB48R	apolipoprotein B48	Hypothetical protein, Lipoprotein,	3777	7745
  		receptor	Receptor
  NM_018699	PRDM5	PR domain	Transcription regulation, DNA-	3778	7746
  		containing 5	binding, Zinc-finger, Metal-binding,
  			Nuclear protein, Repeat
  NM_018728	MYO5C	myosin VC	Myosin, Repeat, ATP-binding,	3779	7747
  			Calmodulin-binding, Actin-binding,
  			Coiled coil, Polymorphism
  NM_018834	MATR3	matrin	3	Nuclear protein, RNA-binding,	3780	7748
  			Repeat, Zinc-finger
  NM_018839	NSFL1C	NSFL1 (p97)	Hypothetical protein	3781	7749
  		cofactor (p47)
  NM_018840	C20orf24	chromosome	20	Alternative splicing, Membrane, SH2	3782	7750
  		open reading frame	domain, SH3 domain, Myristate,
  		24	Phosphorylation, Alternative
  			initiation, Lipoprotein
  NM_018939	PCDHB6	protocadherin beta	6	Calcium-binding, Cell adhesion,	3783	7751
  			Glycoprotein, Signal, Repeat,
  			Transmembrane, Multigene family
  NM_018959	DAZAP1	DAZ associated	Hypothetical protein	3784	7752
  		protein 1
  NM_018961	UBASH3A	ubiquitin associated	Nuclear protein, SH3 domain,	3785	7753
  		and SH3 domain	Alternative splicing
  		containing, A
  NM_018983	NOLA1	nucleolar protein		3786	7754
  		family A, member 1
  		(H/ACA small
  		nucleolar RNPs)
  NM_018996	FLJ20015	KIAA1582 protein	Hypothetical protein	3787	7755
  NM_019002	ETAA16	ETAA16 protein		3788	7756
  NM_019009	TOLLIP	toll interacting	Hypothetical protein, Immune	3789	7757
  		protein	response, Inflammatory response
  NM_019012	PEPP2	phosphoinositol 3-	Hypothetical protein	3790	7758
  		phosphate-binding
  		protein-2
  NM_019018	FLJ11127	hypothetical protein	Hypothetical protein	3791	7759
  		FLJ11127
  NM_019042	FLJ20485	hypothetical protein	Hypothetical protein, tRNA	3792	7760
  		FLJ20485	processing, Lyase
  NM_019057	FLJ10404	hypothetical protein	Hypothetical protein	3793	7761
  		FLJ10404
  NM_019063	EML4	echinoderm	Microtubule, Repeat, WD repeat,	3794	7762
  		microtubule	Hypothetical protein
  		associated protein
  		like 4
  NM_019067	FLJ10613	hypothetical protein	Hypothetical protein	3795	7763
  		FLJ10613
  NM_019084	FLJ10895	hypothetical protein	Hypothetical protein	3796	7764
  		FLJ10895
  NM_019096	GTPBP2	GTP bindingprotein 2	GTP-binding, Protein biosynthesis,	3797	7765
  			Hypothetical protein
  NM_019112	ABCA7	ATP-binding	ATP-binding, Hypothetical protein	3798	7766
  		cassette, sub-family
  		A (ABC1), member 7
  NM_019554	S100A4	S100 calcium	Calcium-binding, 3D-structure	3799	7767
  		binding protein A4
  		(calcium protein,
  		calvasculin,
  		metastasin, murine
  		placental homolog)
  NM_019604	CRTAM	class-I MHC-		3800	7768
  		restricted T cell
  		associated molecule
  NM_019848	P3	solute carrier family	Transmembrane, Transport,	3801	7769
  		10 (sodium/bile acid	Symport
  		cotransporter
  		family),member 3
  NM_019892	PPI5PIV	inositol		3802	7770
  		polyphosphate-5-
  		phosphatase, 72 kDa
  NM_019896	POLE4	polymerase (DNA-	DNA-directed DNA polymerase,	3803	7771
  		directed),epsilon 4	DNA-binding, Nuclear protein
  		(p12 subunit)
  NM_020038	ABCC3	ATP-binding	ATP-binding, Glycoprotein,	3804	7772
  		cassette, sub-family	Transmembrane, Transport, Repeat,
  		C (CFTR/MRP),	Alternative splicing
  		member
  3
  NM_020123	SMBP	SM-11044 binding	Hypothetical protein, Signal,	3805	7773
  		protein	Transmembrane
  NM_020133	LPAAT-	1-acylglycerol-3-	Phospholipid biosynthesis,	3806	7774
  	delta	phosphate O-	Transferase, Acyltransferase,
  		acyltransferase 4	Transmembrane
  		(lysophosphatidic
  		acid acyltransferase,
  		delta)
  NM_020134	DPYSL5	dihydropyrimidinase-	Hypothetical protein	3807	7775
  		like 5
  NM_020135	WHIP	Werner helicase	ATP-binding, Helicase, Hypothetical	3808	7776
  		interactingprotein 1	protein
  NM_020139	LOC56898	dehydrogenase/reductase	Oxidoreductase, Hypothetical protein	3809	7777
  		(SDR family)
  		member 6
  NM_020143	LOC56902	putatative 28 kDa	Hypothetical protein	3810	7778
  		protein
  NM_020149	MEIS2	Meis1, myeloid	Hypothetical protein, Homeobox,	3811	7779
  		ecotropic viral	DNA-binding, Nuclear protein,
  		integration site 1	Alternative splicing
  		homolog 2 (mouse)
  NM_020152	C21orf7	chromosome 21	Alternative splicing, Hypothetical	3812	7780
  		open reading frame 7	protein
  NM_020158	RRP46	exosome component	Exosome, Hydrolase, Nuclease,	3813	7781
  		Rrp46	Exonuclease, rRNA processing,
  			Nuclear protein, RNA-binding,
  			Antigen
  NM_020166	MCCC1	methylcrotonoyl-	Mitochondrion, Ligase, Biotin, ATP-	3814	7782
  		Coenzyme A	binding, Transit peptide,Disease
  		carboxylase
  1	mutation, Polymorphism
  		(alpha)
  NM_020179	FN5	FN5 protein		3815	7783
  NM_020184	CNNM4	cyclin M4	Hypothetical protein	3816	7784
  NM_020188	DC13	DC13 protein		3817	7785
  NM_020193	C11ORF30	chromosome 11	Hypothetical protein	3818	7786
  		open reading frame
  		30
  NM_020198	GK001	GK001 protein	Hypothetical protein	3819	7787
  NM_020200	HHGP	phosphoribosyl	Transferase	3820	7788
  		transferase domain
  		containing 1
  NM_020201	NT5M	5′,3′-nucleotidase,	Nucleotide metabolism, Hydrolase,	3821	7789
  		mitochondrial	Mitochondrion, Nucleotide-binding,
  			Magnesium, Transit peptide, 3D-
  			structure
  NM_020216	RNPEP	arginyl	Aminopeptidase, Hydrolase, Zinc,	3822	7790
  		aminopeptidase	Metalloprotease
  		(aminopeptidase B)
  NM_020229	PRDM11	PR domain	Hypothetical protein	3823	7791
  		containing 11
  NM_020231	MDS010	x 010 protein	Hypothetical protein	3824	7792
  NM_020234	MDS009	x 009 protein	Hypothetical protein	3825	7793
  NM_020236	MRPL1	mitochondrial	Hypothetical protein, Ribosomal	3826	7794
  		ribosomal protein L1	protein
  NM_020239	SPEC1	small protein effector	Hypothetical protein	3827	7795
  		1 of Cdc42
  NM_020243	TOMM22	translocase of outer	Receptor, Translocation, Transport,	3828	7796
  		mitochondrial	Protein transport, Outer membrane,
  		membrane 22	Mitochondrion, Transmembrane
  		homolog (yeast)
  NM_020313	LOC57019	hypothetical protein	Hypothetical protein	3829	7797
  		LOC57019
  NM_020314	MGC16824	esophageal cancer	Hypothetical protein	3830	7798
  		associated protein
  NM_020322	ACCN3	amiloride-sensitive	Ionic channel	3831	7799
  		cation channel 3
  NM_020344	SLC24A2	solute carrier family	Vision, Transport, Antiport, Symport,	3832	7800
  		24	Calcium transport, Potassium
  		(sodium/potassium/calcium	transport, Sodium transport,
  		exchanger),	Transmembrane, Glycoprotein,
  		member 2	Signal, Repeat, Alternative splicing
  NM_020347	LZTFL1	leucine zipper		3833	7801
  		transcription factor-
  		like 1
  NM_020350	AGTRAP	angiotensin II	Receptor	3834	7802
  		receptor-associated
  		protein
  NM_020357	PCNP	PEST-containing	Nuclear protein	3835	7803
  		nuclear protein
  NM_020360	PLSCR3	phospholipid	Hypothetical protein,	3836	7804
  		scramblase 3	Transmembrane, Lipoprotein,
  			Calcium-binding, SH3-binding,
  			Repeat, Phosphorylation, Palmitate,
  			Polymorphism
  NM_020365	EIF2B3	eukaryotic	Initiation factor, Protein biosynthesis,	3837	7805
  		translation initiation	Alternative splicing, Disease
  		factor 2B,subunit 3	mutation, Hypothetical protein
  		gamma, 58 kDa
  NM_020366	RPGRIP1	retinitis pigmentosa		3838	7806
  		GTPaseregulator
  		interacting protein
  1
  NM_020370	GPR84	G protein-coupled	Receptor	3839	7807
  		receptor 84
  NM_020371	AVEN	apoptosis, caspase	Apoptosis	3840	7808
  		activation inhibitor
  NM_020385	XPMC2H	XPMC2 prevents	Hypothetical protein	3841	7809
  		mitotic catastrophe 2
  		homolog (Xenopus
  		laevis)
  NM_020390	EIF5A2	eukaryotic	Initiation factor, Hypothetical protein	3842	7810
  		translation initiation
  		factor 5A2
  NM_020394	LOC57116	zinc finger protein	Metal-binding, Zinc, Zinc-finger	3843	7811
  		SBZF3
  NM_020399	PIST	golgi associated	Hypothetical protein	3844	7812
  		PDZ and coiled-coil
  		motif containing
  NM_020401	NUP107	nuclear pore	Nuclear protein, Transport	3845	7813
  		complex protein
  NM_020406	PRV1	polycythemia rubra	Signal, Receptor	3846	7814
  		vera 1
  NM_020408	CGI-203	chromosome 6 open	Hypothetical protein	3847	7815
  		reading frame 149
  NM_020410	CGI-152	cation-transporting	Hydrolase, Transmembrane,	3848	7816
  		ATPase	Phosphorylation, Magnesium, ATP-
  			binding, Alternative splicing,
  			Hypothetical protein
  NM_020414	DDX24	DEAD (Asp-Glu-Ala-	Hydrolase, Helicase, ATP-binding,	3849	7817
  		Asp) box polypeptide	RNA-binding
  		24
  NM_020415	RETN	resistin	Hormone, Signal, Diabetes mellitus,	3850	7818
  			Obesity
  NM_020466	DJ122O8.2	hypothetical protein	Hypothetical protein	3851	7819
  		dJ122O8.2
  NM_020469	ABO	ABO blood group	Transferase, Glycosyltransferase,	3852	7820
  		(transferase A, alpha	Blood group antigen, Golgi stack,
  		1-3-N-	Metal-binding, Manganese, Signal-
  		acetylgalactosaminyl	anchor, Transmembrane,
  		transferase;	Glycoprotein, Polymorphism, 3D-
  		transferase B, alpha	structure
  		1-3-
  		galactosyltransferase)
  NM_020480	ANK1	ankyrin	1,	ANK repeat, Repeat, Cytoskeleton,	3853	7821
  		erythrocytic	Alternative splicing, Phosphorylation,
  			Lipoprotein, Disease mutation,
  			Elliptocytosis, Polymorphism
  NM_020484	AF011757	Homo sapiens		3854	7822
  		RAGE binding
  		protein (AF011757),
  		mRNA.
  NM_020530	OSM	oncostatin M	Growth regulation, Cytokine,	3855	7823
  			Glycoprotein, Signal, 3D-structure
  NM_020533	MCOLN1	mucolipin	1	Hypothetical protein, Ionic channel,	3856	7824
  			Transmembrane
  NM_020548	DBI	diazepam binding	Transport, Lipid-binding, Acetylation,	3857	7825
  		inhibitor (GABA	Alternative splicing
  		receptor modulator,
  		acyl-Coenzyme A
  		binding protein)
  NM_020632	ATP6V0A4	ATPase, H+	Hydrogen ion transport,	3858	7826
  		transporting,	Transmembrane, Glycoprotein,
  		lysosomal V0	Disease mutation, Hypothetical
  		subunit aisoform 4	protein
  NM_020639	ANKRD3	ankyrin repeat	ANK repeat, Repeat, Hypothetical	3859	7827
  		domain 3	protein, ATP-binding, Kinase,
  			Serine/threonine-protein kinase,
  			Transferase, Alternative splicing
  NM_020648	TWSG1	twisted gastrulation	Hypothetical protein, Signal	3860	7828
  		homolog 1
  		(Drosophila)
  NM_020652	ZNF286	zinc finger protein	Transcription regulation, Zinc-finger,	3861	7829
  		286	Metal-binding, Nuclear protein, DNA-
  			binding, Repeat
  NM_020659	TTYH1	tweety homolog 1		3862	7830
  		(Drosophila)
  NM_020664	DECR2	2,4-dienoyl CoA	Hypothetical protein, Oxidoreductase	3863	7831
  		reductase 2,
  		peroxisomal
  NM_020686	NPD009	4-aminobutyrate		3864	7832
  		aminotransferase
  NM_020905	RDH14	retinol	Oxidoreductase, NADP	3865	7833
  		dehydrogenase 14
  		(all-trans and 9-cis)
  NM_020980	AQP9	aquaporin	9	Transport, Repeat, Transmembrane	3866	7834
  NM_020983	ADCY6	adenylate cyclase	6	Lyase, cAMP biosynthesis,	3867	7835
  			Transmembrane, Glycoprotein,
  			Repeat, Metal-binding, Magnesium,
  			Alternative splicing
  NM_020995	HPR	haptoglobin-related	Hydrolase, Protease, Serine	3868	7836
  		protein	protease
  NM_020999	NEUROG3	neurogenin 3		3869	7837
  NM_021018	HIST1H3F	histone 1, H3f	Nuclear protein, Chromosomal	3870	7838
  			protein, DNA-binding, Nucleosome
  			core, Multigene family, Acetylation,
  			Methylation
  NM_021019	MYL6	myosin, light	Myosin, Muscle protein, Acetylation,	3871	7839
  		polypeptide 6, alkali,	Alternative splicing, Multigene family
  		smooth muscle and
  		non-muscle
  NM_021025	TLX3	T-cell leukemia,	Homeobox, DNA-binding, Nuclear	3872	7840
  		homeobox 3	protein, Developmental protein
  NM_021031	CYCL	Homo sapiens	Hypothetical protein	3873	7841
  		cytochrome c-like
  		antigen (CYCL),
  		mRNA
  NM_021039	S100A14	S100 calcium	Transcription regulation, DNA-	3874	7842
  		binding protein A14	binding, Nuclear protein,
  		(calgizzarin)	Hypothetical protein, Calcium-
  			binding
  NM_021074	NDUFV2	NADH	Oxidoreductase, NAD, Ubiquinone,	3875	7843
  		dehydrogenase	Mitochondrion, Transit peptide,
  		(ubiquinone)	Metal-binding, Iron-sulfur, Iron, 2Fe—2S,
  		flavoprotein 2,	Polymorphism
  		24 kDa
  NM_021075	NDUFV3	NADH	Hypothetical protein	3876	7844
  		dehydrogenase
  		(ubiquinone)
  		flavoprotein 3,
  		10 kDa
  NM_021078	GCN5L2	GCN5 general	Transcription regulation,	3877	7845
  		control of amino-acid	Transferase, Nuclear protein,
  		synthesis 5-like 2	Bromodomain, Alternative splicing,
  		(yeast)	3D-structure
  NM_021079	NMT1	N-	Acyltransferase, Transferase,	3878	7846
  		myristoyltransferase 1	Alternative splicing
  NM_021090	MTMR3	myotubularin related	Hydrolase, Zinc-finger, Alternative	3879	7847
  		protein 3	splicing
  NM_021103	TMSB10	thymosin,beta 10	Actin-binding, Cytoskeleton,	3880	7848
  			Acetylation
  NM_021106	RGS3	regulator of G-	Hypothetical protein, Signal	3881	7849
  		protein signalling 3	transduction inhibitor, Alternative
  			splicing, Phosphorylation
  NM_021131	PPP2R4	protein phosphatase	Alternative splicing	3882	7850
  		2A, regulatory
  		subunit B′ (PR 53)
  NM_021173	POLD4	polymerase (DNA-	DNA-directed DNA polymerase,	3883	7851
  		directed),delta 4	DNA replication, Nuclear protein
  NM_021178	HEI10	chromosome 14	Ubl conjugation pathway, Ligase,	3884	7852
  		open reading frame	Nuclear protein, Metal-binding, Zinc,
  		18	Coiled coil, Zinc-finger,
  			Phosphorylation, Ubl conjugation
  NM_021197	WFDC1	WAP four-disulfide	Serine protease inhibitor, Signal	3885	7853
  		core domain 1
  NM_021198	NLI-IF	CTD (carboxy-	Hypothetical protein, Nuclear protein	3886	7854
  		terminal domain,
  		RNA polymerase II,
  		polypeptide A)small
  		phosphatase
  1
  NM_021199	SQRDL	sulfide quinone	Oxidoreductase, Flavoprotein, FAD,	3887	7855
  		reductase-like	NADP, Mitochondrion, Transit
  		(yeast)	peptide, Polymorphism
  NM_021212	ZF	HCF-binding	DNA-binding, Nuclear protein	3888	7856
  		transcription factor
  		Zhangfei
  NM_021238	TERA	TERA protein	Hypothetical protein	3889	7857
  NM_021242	STRAIT11499	MID1 interacting	Hypothetical protein	3890	7858
  		G12-like protein
  NM_021251	CAPN10	calpain 10	Hydrolase, Thiol protease, Repeat,	3891	7859
  			Alternative splicing, Polymorphism,
  			Diabetes mellitus
  NM_021259	TMEM8	transmembrane	Cell adhesion, Signal,	3892	7860
  		protein 8 (five	Transmembrane, EGF-like domain,
  		membrane-spanning	Glycoprotein
  		domains)
  S73288	small	small proline-rich		3893	7861
  	proline-rich	protein 1A
  	protein
  	SPRK
  S74639	IGHM	Clone I50	Immunoglobulin domain,	3894	7862
  		immunoglobulin	Immunoglobulin C region,
  		heavy chain variable	Glycoprotein, Repeat, Pyrrolidone
  		region mRNA, partial	carboxylic acid, Polymorphism,
  		cds	Membrane, Hypothetical protein,
  			Receptor, T-cell, Signal
  S77356	ATP5O	ATP synthase, H+	Hydrolase, ATP synthesis, CF(1),	3895	7863
  		transporting,	Hydrogen ion transport,
  		mitochondrial F1	Mitochondrion, Transit peptide,
  		complex, O subunit	Polymorphism
  		(oligomycin
  		sensitivity conferring
  		protein)
  S80864	cytochrome	cytochrome c-like	Hypothetical protein	3896	7864
  	c-like	antigen
  	polypeptide
  S90469	POR	P450 (cytochrome)	Oxidoreductase, Flavoprotein, FMN,	3897	7865
  		oxidoreductase	FAD, NADP, Endoplasmic reticulum,
  			Membrane, Acetylation,
  			Polymorphism, 3D-structure
  U00946	KIAA0344	protein kinase, lysine	Hypothetical protein, ATP-binding,	3898	7866
  		deficient 1	Kinase, Serine/threonine-protein
  			kinase, Transferase
  U01147	ABR	active BCR-related	Guanine-nucleotide releasing factor,	3899	7867
  		gene	Alternative splicing
  U02032	RPL23A	ribosomal protein	Ribosomal protein, rRNA-binding	3900	7868
  		L23a
  U09196	POLD4	polymerase (DNA-	DNA-directed DNA polymerase,	3901	7869
  		directed),delta 4	DNA replication, Nuclear protein
  U14383	MUC8	Human mucin		3902	7870
  		(MUC8) mRNA,
  		partial cds.
  U20180	IREB2	iron-responsive	Iron-sulfur, 4Fe—4S, RNA-binding,	3903	7871
  		element binding	Hypothetical protein
  		protein
  2
  U25750		hypothetical protein	Hypothetical protein	3904	7872
  		MGC20235
  U36759	PTCRA	pre T-cell antigen		3905	7873
  		receptor alpha
  U37689	POLR2H	polymerase (RNA) II	Transferase, DNA-directed RNA	3906	7874
  		(DNA directed)	polymerase, Transcription, Nuclear
  		polypeptide H	protein
  U41387	DDX21	DEAD (Asp-Glu-Ala-	Helicase, RNA-binding, ATP-binding,	3907	7875
  		Asp) box polypeptide	Nuclear protein, Antigen, Repeat
  		21
  U43431	TOP3A	topoisomerase	Isomerase, Topoisomerase, DNA-	3908	7876
  		(DNA) III alpha	binding, Repeat, Zinc-finger,
  			Alternative splicing, Polymorphism
  U43604		Human unidentified		3909	7877
  		mRNA, partial
  		sequence.
  U56725	HSPA2	Human heat shock	ATP-binding, Chaperone, Heat	3910	7878
  		protein mRNA,	shock, Multigene family
  		complete cds.
  U58033	MTMR2	myotubularin related	Hydrolase, Charcot-Marie-Tooth	3911	7879
  		protein 2	disease
  U64205	MARK3	MAP/microtubule	Transferase, Serine/threonine-	3912	7880
  		affinity-regulating	protein kinase, ATP-binding,
  		kinase 3	Alternative splicing, Plasmid
  U66702	PTPRN2	protein tyrosine	Hypothetical protein, Hydrolase,	3913	7881
  		phosphatase,	Receptor, Glycoprotein, Signal,
  		receptor type, N	Transmembrane, Diabetes mellitus,
  		polypeptide 2	Alternative splicing
  U68382	MAN2B1	mannosidase, alpha,	Glycosidase, Hydrolase,	3914	7882
  		class 2B,member 1	Glycoprotein, Lysosome, Zymogen,
  			Signal, Disease mutation,
  			Polymorphism
  U68494		solute carrier family		3915	7883
  		30 (zinc transporter),
  		member 1
  U69127	FUBP3	far upstream	Transcription regulation, Transacting	3916	7884
  		element (FUSE)	factor, Nuclear protein, DNA-
  		bindingprotein 3	binding, Repeat, Alternative splicing
  U69645	ZNF32	zinc finger protein 32	Hypothetical protein, Metal-binding,	3917	7885
  		(KOX 30)	Zinc, Zinc-finger, Transcription
  			regulation, DNA-binding, Nuclear
  			protein, Repeat
  U72882	IFI35	interferon-induced	Interferon induction, Alternative	3918	7886
  		protein 35	splicing
  U79246	DIS3	FLJ22624 protein	Hypothetical protein	3919	7887
  U79260	MGC5149	fatso	Hypothetical protein	3920	7888
  U79277		tyrosine 3-	Neurone, Phosphorylation,	3921	7889
  		monooxygenase/tryptophan	Acetylation, Multigene family, 3D-
  		5-	structure
  		monooxygenase
  		activation protein,
  		zeta polypeptide
  U79280	PIPPIN	RNA-binding protein	Hypothetical protein, mRNA	3922	7890
  		pippin	processing, RNA-binding, Nuclear
  			protein
  U79282		hypothetical protein	Hypothetical protein	3923	7891
  		LOC137886
  U79290		Human clone 23908		3924	7892
  		mRNA sequence
  U79298	MGC39325	hypothetical protein	Hypothetical protein	3925	7893
  		MGC39325
  U79458	WBP2	Human WW domain	Hypothetical protein	3926	7894
  		binding protein-2
  		mRNA, complete
  		cds.
  U80628	TK2	thymidine kinase	2,	Kinase, Transferase, DNA synthesis,	3927	7895
  		mitochondrial	ATP-binding, Mitochondrion, Transit
  			peptide, Alternative splicing
  U82277	LILRA2	leukocyte	Immune response, Receptor,	3928	7896
  		immunoglobulin-like	Repeat, Signal, Transmembrane,
  		receptor, subfamily	Immunoglobulin domain,
  		B (with TM and ITIM	Glycoprotein, Antigen, Alternative
  		domains),member 1	splicing, Polymorphism, Multigene
  			family, Phosphorylation, 3D-structure
  U83115	AIM1	absent inmelanoma 1	Repeat, Lectin	3929	7897
  U90878	PDLIM1	PDZ and LIM	Cytoskeleton, LIM domain, Metal-	3930	7898
  		domain 1 (elfin)	binding, Zinc
  U90909	MISS	chromosome 14	Hypothetical protein	3931	7899
  		open reading frame
  		32
  U90911	WIRE	WIRE protein		3932	7900
  U90916		sortilin-related	Endocytosis, Receptor,	3933	7901
  		receptor, L(DLR	Transmembrane, EGF-like domain,
  		class) A repeats-	Repeat, Glycoprotein, LDL, Lipid
  		containing	transport, Cholesterol metabolism,
  			Signal
  W61000_RC	NORE1	Ras association	Hypothetical protein	3934	7902
  		(RaIGDS/AF-6)
  		domain family 5
  X00437	IGHM	Human mRNA for T-	Immunoglobulin domain,	3935	7903
  		cell specific protein.	Immunoglobulin C region,
  			Glycoprotein, Repeat, Pyrrolidone
  			carboxylic acid, Polymorphism,
  			Membrane, Hypothetical protein,
  			Receptor, T-cell, Signal
  X04201	TPM3	tropomyosin	3	Hypothetical protein, Muscle protein,	3936	7904
  			Cytoskeleton, Actin-binding, Coiled
  			coil, Alternative splicing, Multigene
  			family, Disease mutation
  X04526	GNB1	Human liver mRNA	Transducer, Repeat, WD repeat,	3937	7905
  		for beta-subunit	Multigene family, 3D-structure
  		signal transducing
  		proteins Gs/Gi (beta-
  		G).
  X07618	CYP2D6	cytochrome P450,	Heme, Monooxygenase,	3938	7906
  		family 2, subfamily	Oxidoreductase, Electron transport,
  		D,polypeptide 6	Membrane, Microsome,
  			Endoplasmic reticulum,
  			Polymorphism
  X13956	MGC10471	hypothetical protein		3939	7907
  		MGC10471
  X15183	HSPCA	heat shock 90 kDa	Heat shock, Chaperone, ATP-	3940	7908
  		protein 1, alpha	binding, Phosphorylation, 3D-
  			structure, Hypothetical protein,
  			Plasmid
  X51630	WT1	Wilms tumor 1	Zinc-finger, Metal-binding, DNA-	3941	7909
  			binding, Repeat, Nuclear protein,
  			Transcription regulation, Alternative
  			splicing, Anti-oncogene, Disease
  			mutation, Chromosomal
  			translocation, 3D-structure
  X52015	IL1RN	interleukin 1 receptor	Glycoprotein, Signal, Alternative	3942	7910
  		antagonist	splicing, 3D-structure
  X52882	TCP1	t-complex 1	Chaperone, ATP-binding, Multigene	3943	7911
  			family
  X56789	TTS-2.2	transport-secretion	Hypothetical protein	3944	7912
  		protein 2.2
  X57352	IFITM3	interferon induced	Interferon induction,	3945	7913
  		transmembrane	Transmembrane
  		protein 3 (1-8U)
  X58536	HLA-C	major	Glycoprotein, Signal,	3946	7914
  		histocompatibility	Transmembrane, Hypothetical
  		complex, class I, C	protein, MHC, MHC I,
  			Polymorphism, 3D-structure,
  			Alternative splicing
  X58794	AZU1	azurocidin 1	Serine protease homolog,	3947	7915
  		(cationic	Glycoprotein, Chemotaxis, Antibiotic,
  		antimicrobial protein	Heparin-binding, Signal, 3D-
  		37)	structure
  X59417	PSMA6	proteasome	Proteasome, Hydrolase, Protease,	3948	7916
  		(prosome,	Threonine protease
  		macropain) subunit,
  		alpha type, 6
  X61079	IGHM	T cell receptor	Immunoglobulin domain,	3949	7917
  		alpha-chain (TCR	Immunoglobulin C region,
  		Valpha20Jalpha9.14)	Glycoprotein, Repeat, Pyrrolidone
  		mRNA, partial cds.	carboxylic acid, Polymorphism,
  			Membrane, Hypothetical protein,
  			Receptor, T-cell, Signal
  X62535	DGKA	diacylglycerol	Hypothetical protein, Kinase,	3950	7918
  		kinase,alpha 80 kDa	Transferase, Calcium-binding,
  			Phorbol-ester binding, Repeat,
  			Multigene family
  X63417	IRLB	c-myc promoter-	DNA-binding, Hypothetical protein	3951	7919
  		binding protein
  X69115	ZNF37A	zinc finger protein	Hypothetical protein, Metal-binding,	3952	7920
  		37a (KOX 21)	Nuclear protein, Zinc, Zinc-finger,
  			Transcription regulation, DNA-
  			binding, Repeat
  X71490	ATP6V0D1	H. sapiensmRNA for	Hydrolase, ATP synthesis, Hydrogen	3953	7921
  		vacuolar proton	ion transport
  		ATPase, subunit D.
  X78817	ARHGAP4	Rho GTPase	GTPase activation, SH3 domain,	3954	7922
  		activatingprotein 4	Coiled coil
  X87949	HSPA5	heat shock 70 kDa	ATP-binding, Endoplasmic reticulum,	3955	7923
  		protein 5 (glucose-	Signal
  		regulated protein,
  		78 kDa)
  X89214	hpr	H. sapiensmRNA for	Hydrolase, Protease, Serine	3956	7924
  		haptoglobin related	protease
  		protein.
  X94232	MAPRE2	microtubule-	T-cell	3957	7925
  		associated protein,
  		RP/EB family,
  		member 2
  X98258	MPHOSPH9	M-phase	Phosphorylation, Golgi stack,	3958	7926
  		phosphoprotein 9	Membrane, Coiled coil
  X98261	ZWINTAS	ZW10 interactor	Phosphorylation, Nuclear protein,	3959	7927
  			Coiled coil
  X98411	MYO1F	myosin IF	Myosin, ATP-binding, Actin-binding,	3960	7928
  			Calmodulin-binding, SH3 domain,
  			Multigene family
  Y00433	GPX1	glutathione	Oxidoreductase, Peroxidase,	3961	7929
  		peroxidase 1	Selenium, Selenocysteine,
  			Erythrocyte, Polymorphism,
  			Hypothetical protein
  Y00816	CR1	complement	Complement pathway, Glycoprotein,	3962	7930
  		component (3b/4b)	Transmembrane, Repeat, Signal,
  		receptor 1, including	Receptor, Sushi, Blood group
  		Knops blood group	antigen, Polymorphism, Pyrrolidone
  		system	carboxylic acid, 3D-structure
  Y14442	OR1F1	olfactory receptor,	G-protein coupled receptor,	3963	7931
  		family 1, subfamily	Transmembrane, Glycoprotein,
  		F,member 1	Multigene family, Olfaction
  Y18490	LST1	leukocyte specific	Immune response, Cell shape,	3964	7932
  		transcript 1	Transmembrane, Alternative splicing
  Z15114	PRKCG	protein kinase C,	Transferase, Serine/threonine-	3965	7933
  		gamma	protein kinase, ATP-binding,
  			Calcium-binding, Metal-binding,
  			Zinc, Repeat, Phorbol-ester binding,
  			Phosphorylation, Polymorphism
  Z34893	IGHM	Clone P2-114 anti-	Immunoglobulin domain,	3966	7934
  		oxidized LDL	Immunoglobulin C region,
  		immunoglobulin	Glycoprotein, Repeat, Pyrrolidone
  		heavy chain Fab	carboxylic acid, Polymorphism,
  		mRNA, partial cds	Membrane, Hypothetical protein,
  			Receptor, T-cell, Signal
  Z48314	MUC5AC	mucin	5, subtypes A	Repeat, Glycoprotein, Signal,	3967	7935
  		and C,	Polymorphism, Hypothetical protein
  		tracheobronchial/gastric
  Z49105	SSX2	synovial sarcoma, X	Chromosomal translocation, Proto-	3968	7936
  		breakpoint 2	oncogene, Multigene family,
  			Transcription regulation

7. REFERENCES CITED
• All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.
• Many modifications and variations of the present invention can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. The specific embodiments described herein are offered by way of example only, and the invention is to be limited only by the terms of the appended claims along with the full scope of equivalents to which such claims are entitled.

Claims (15)

What is claimed:

1. A computer-implemented method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising:

(a) classifying, on a computer, a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as an IM-sensitive profile or an IM-resistant profile, wherein said gene products are respectively products of at least five of the genes listed in Table 4;

(b) determining said patient as responsive to IM treatment if said marker profile is classified as an IM-sensitive profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an IM-resistant profile; and

(c) outputting to a user, a user interface device, a monitor, a computer readable storage medium, a local computer, or a computer that is part of a network; or displaying; the determination resulting from step (b).

2. The method ofclaim 1, wherein the gene products are products consisting of 5, 10, 15, 20, 25, 30, 40, 60, 70, 80, 90, 100, 200, or 228 of the genes listed in Table 4.

3. The method ofclaim 1, further comprising obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.

4. The method ofclaim 3, wherein said cell sample is a sample from bone marrow or peripheral blood.

5. The method ofclaim 1, wherein said classifying is carried out by a method comprising using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is an IM-sensitive profile or an IM-resistant profile.

6. The method ofclaim 1, wherein the gene products are selected from the group consisting of at least 5, 6, 7, or 8 of the genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, tyrosine kinase oncogene FYN, TCF7, guanine nucleotide binding proteins GNAZ and GNG11, and MAF.

7. The method ofclaim 1, wherein each of said gene products is a gene transcript.

8. The method ofclaim 7, wherein measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.

9. The method ofclaim 7, wherein measurement of each said gene transcript is obtained by quantitative reverse transcriptase PCR (qRT-PCR).

10. The method ofclaim 1, wherein each of said plurality of gene products is a protein.

11. The method ofclaim 1, wherein said classifying is carried out using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is a IM resistant profile or an IM responsive profile.

12. The method ofclaim 11, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with an IM resistant template profile and/or an IM responsive template profile, wherein said IM resistant template profile and IM responsive template profile are obtained from a training population comprising IM resistant patients and IM responsive patients, respectively; and (ii) classifying said marker profile as an IM resistant profile if said marker profile has a high similarity to said IM resistant template profile and/or has a low similarity to said IM resistant template profile, or classifying said marker profile as an IM responsive profile if said marker profile has a high similarity to said IM responsive template profile and/or has a low similarity to said IM resistant template profile, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

13. The method ofclaim 11, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with said IM resistant template profile or said IM responsive template profile; and (ii) classifying said marker profile as an IM resistant profile if said marker profile has a high similarity to said IM resistant template profile or has a low similarity to said IM responsive template profile, or classifying said marker profile as an IM responsive profile if said marker profile has a high similarity to said IM responsive template profile or has a low similarity to said IM resistant template profile, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

14. The method ofclaim 12, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with said IM resistant template profile and said IM responsive template profile; and (ii) classifying said marker profile as an IM resistant profile if said marker profile has a higher similarity to said IM resistant template profile than to said IM responsive template profile, or classifying said marker profile as a IM responsive profile if said marker profile has a higher similarity to said IM responsive template profile than to said IM resistant template profile.

15. The method ofclaim 11, wherein said progression classifier is based on a classification method selected from the group consisting of an artificial neural network, a support vector machine, logic regression, linear or quadratic discriminant analysis, decision trees, principal component analysis, and nearest neighbor classifier analysis.

Images