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Sodium- and chloride-dependent glycine transporter 1

From Wikipedia, the free encyclopedia
(Redirected fromGlycine transporter 1)
Protein-coding gene in the species Homo sapiens

SLC6A9
Identifiers
AliasesSLC6A9, GLYT1, Glycine transporter 1, solute carrier family 6 member 9, GCENSG
External IDsOMIM:601019;MGI:95760;HomoloGene:5050;GeneCards:SLC6A9;OMA:SLC6A9 - orthologs
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for SLC6A9
Genomic location for SLC6A9
Band1p34.1Start43,991,500bp[1]
End44,031,467bp[1]
Gene location (Mouse)
Chromosome 4 (mouse)
Chr.Chromosome 4 (mouse)[2]
Chromosome 4 (mouse)
Genomic location for SLC6A9
Genomic location for SLC6A9
Band4 D1|4 53.62 cMStart117,691,703bp[2]
End117,732,395bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • C1 segment

  • skin of leg

  • skin of abdomen

  • right adrenal gland

  • stromal cell of endometrium

  • left adrenal gland

  • right adrenal cortex

  • left adrenal cortex

  • mucosa of transverse colon

  • mucosa of esophagus
Top expressed in
  • neural layer of retina

  • secondary oocyte

  • retinal pigment epithelium

  • fetal liver hematopoietic progenitor cell

  • deep cerebellar nuclei

  • primary oocyte

  • zygote

  • lumbar subsegment of spinal cord

  • medulla oblongata

  • dorsal tegmental nucleus
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo /QuickGO
Orthologs
SpeciesHumanMouse
Entrez

6536

14664

Ensembl

ENSG00000196517

ENSMUSG00000028542

UniProt

P48067

P28571

RefSeq (mRNA)
NM_001024845
NM_001261380
NM_006934
NM_201649
NM_001328626

NM_001328627
NM_001328628
NM_001328629
NM_001328630

NM_008135
NM_001355175
NM_001369016
NM_001369017

RefSeq (protein)
NP_001020016
NP_001248309
NP_001315555
NP_001315556
NP_001315557

NP_001315558
NP_001315559
NP_008865
NP_964012

NP_032161
NP_001342104
NP_001355945
NP_001355946

Location (UCSC)Chr 1: 43.99 – 44.03 MbChr 4: 117.69 – 117.73 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Sodium- and chloride-dependent glycine transporter 1, also known asglycine transporter 1, is aprotein that in humans is encoded by theSLC6A9gene which is promising therapeutic target for treatment of diabetes and obesity.[5][6][7][8]

Selective inhibitors

[edit]

Elevation of extracellular synapticglycine concentration by blockade of GlyT1 has been hypothesized to potentiateNMDA receptor function in vivo and to represent a rational approach for the treatment ofschizophrenia and cognitive disorders. Several drug candidates have reached clinical trials.[9]

  • ASP2535[10]
  • Bitopertin (RG1678), which has enteredphase II trials for the treatment of schizophrenia[11]
  • Iclepertin (BI 425809) by Boehringer Ingelheim which is thought to improve cognitive impairment due to schizophrenia
  • Org 25935 (Sch 900435)
  • PF-03463275 (in phase II trial)
  • Pesampator (PF-04958242) by Pfizer
  • Sarcosine which is thought to improve cognitive impairment due to schizophrenia

Pathological mutations

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Mutations of the gene may cause a severe metabolic disorder discovered in 2016 and calledglycine encephalopathy with normal serum glycine (OMIM 617301), also known as GlyT1 encephalopathy.

See also

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References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000196517 –Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000028542 –Ensembl, May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^Sinha JK, Durgvanshi S, Verma M, Ghosh S (June 2023)."Investigation of SLC6A9 and SLC5A1 as a promising therapeutic target for obesity and diabetes using in silico characterization, 3D structure prediction and molecular docking analysis".Alzheimer's & Dementia.19 (S1).doi:10.1002/alz.064229.ISSN 1552-5260.
  6. ^Kim KM, Kingsmore SF, Han H, Yang-Feng TL, Godinot N, Seldin MF, et al. (April 1994). "Cloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes".Molecular Pharmacology.45 (4):608–617.doi:10.1016/S0026-895X(25)10145-4.PMID 8183239.
  7. ^Jones EM, Fernald A, Bell GI, Le Beau MM (Nov 1995). "Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization".Cytogenetics and Cell Genetics.71 (3): 211.doi:10.1159/000134110.PMID 7587377.
  8. ^"Entrez Gene: SLC6A9 solute carrier family 6 (neurotransmitter transporter, glycine), member 9".
  9. ^Harvey RJ, Yee BK (November 2013). "Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain".Nature Reviews. Drug Discovery.12 (11):866–885.doi:10.1038/nrd3893.PMID 24172334.S2CID 28022131.
  10. ^Harada K, Nakato K, Yarimizu J, Yamazaki M, Morita M, Takahashi S, et al. (June 2012). "A novel glycine transporter-1 (GlyT1) inhibitor, ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole), improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease".European Journal of Pharmacology.685 (1–3):59–69.doi:10.1016/j.ejphar.2012.04.013.PMID 22542656.
  11. ^Pinard E, Alanine A, Alberati D, Bender M, Borroni E, Bourdeaux P, et al. (June 2010). "Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia".Journal of Medicinal Chemistry.53 (12):4603–4614.doi:10.1021/jm100210p.PMID 20491477.

Further reading

[edit]
By group
SLC1–10
(1):
(2):
(3):
(4):
(5):
(6):
(7):
(8):
(9):
(10):
SLC11–20
(11):
(12):
(13):
(14):
(15):
(16):
(17):
(18):
(19):
(20):
SLC21–30
(21):
(22):
(23):
(24):
(25):
(26):
(27):
(28):
(29):
(30):
SLC31–40
(31):
(32):
(33):
(34):
(35):
(36):
(37):
(38):
(39):
(40):
SLC41–48
(41):
(42):
(43):
(44):
(45):
(46):
(47):
(48):
SLCO1–4
Symporter,Cotransporter
Antiporter (exchanger)
Receptor
(ligands)
GlyRTooltip Glycine receptor
NMDARTooltip N-Methyl-D-aspartate receptor
Transporter
(blockers)
GlyT1Tooltip Glycine transporter 1
GlyT2Tooltip Glycine transporter 2
AMPARTooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
KARTooltip Kainate receptor
NMDARTooltip N-Methyl-D-aspartate receptor
Group I
mGluR1Tooltip Metabotropic glutamate receptor 1
mGluR5Tooltip Metabotropic glutamate receptor 5
Group II
mGluR2Tooltip Metabotropic glutamate receptor 2
mGluR3Tooltip Metabotropic glutamate receptor 3
Group III
mGluR4Tooltip Metabotropic glutamate receptor 4
mGluR6Tooltip Metabotropic glutamate receptor 6
mGluR7Tooltip Metabotropic glutamate receptor 7
mGluR8Tooltip Metabotropic glutamate receptor 8
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