| FAM204A | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | FAM204A, C10orf84, bA319I23.1, family with sequence similarity 204 member A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI:1289174;HomoloGene:41463;GeneCards:FAM204A;OMA:FAM204A - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
FAM204A (family with sequence similarity 204 member A) is aprotein-coding gene that encodes the nuclear protein FAM204A in humans. The gene is located onchromosome 10 at position 10q26.11 and is ubiquitously expressed in human tissues.
FAM204A spans approximately 44kilobases (kb) at chromosomal position 118.30 to 118.34 megabases (Mb) on theGRCh38 assembly and is transcribed from theminus (complementary) DNA strand.[5] It contains eight exons and produces two validated mRNA isoforms (NM_022063.3 and NM_001134672.2) that encode the same 233‑amino acid protein.[5] Other identifiers includeC10orf84 andbA319I23.1.[5]
FAM204A's upstream neighbor isRAB11FIP2, which encodes a protein predicted to mediate protein kinase binding and dimerization and is expressed ubiquitously, with localization in the nucleoplasm and endosomal compartments.[6] Its downstream neighbor is the long non‐coding RNACASC2 (cancer susceptibility candidate 2), implicated as a tumor suppressor and consistently observed to be downregulated in multiple cancer types.[7]
The human FAM204A protein is 233amino acids in length with a molecular weight of approximately 27kilodaltons (kDa) and a predictedisoelectric point (pI) near 7.7.[8]
FAM204A islysine-rich and highly charged; nearly 40% of residues are basic or acidic. A lysine/arginine cluster between residues 95–114 resembles a nuclear localization signal (NLS) or nucleic acid-binding motif. Nosignal peptides ortransmembrane regions are predicted, consistent with a soluble nuclear protein.
FAM204A is predicted to localize to the nucleus with high confidence by multiple computational tools.DeepLoc assigns a 0.90 probability for nuclear residency, whilePSORT II identifies several monopartite and bipartitenuclear localization signals (e.g., KRRK at residue 100,bipartite motif KKHSEQKSTTSRFRGKR at residue 85).[9][10] SAPS compositional analysis highlights a positively charged segment (residues 95–114) typical of nuclear localization ornucleic acid-binding motifs.[8]Immunohistochemistry data show nuclear and nucleolar localization of FAM204A in human cells.[11]
Predictedpost-translational modifications include multiplephosphorylation sites (serine 17, serine 40, serine 93–105) andtyrosine phosphorylation (tyrosine 65, tyrosine 232), as well as motifs forSUMOylation andacetylation.[12][13] Experimental evidence supports phosphorylation at serine 152 (S152),ubiquitylation at lysine 128 (K128) and lysine 169 (K169), and acetylation at lysine 221 (K221) and lysine 222 (K222).[14]
AlphaFold predicts a largely disordered protein with a singleα‑helical domain spanning residues 126–211 (CATH fold 1.10.287) and high model confidence (pLDDT ≈94).[15] This structured region may provide a stable core for interactions, while flanking regions remain intrinsically disordered.
FAM204A is broadly conserved acrossopisthokonts, withorthologous proteins identified inmammals,birds,reptiles,amphibians,fish, basalchordates (e.g.,lancelets andtunicates), basalmetazoans (e.g.,sponges andcnidarians), andfungi.[5][16]
Vertebrate orthologs share higher sequence identity (~35–~90%) with human FAM204A, while more distant orthologs retain a more conserved C‑terminal region despite overall lower identity (~21-30).[17][18]
| Common name | Scientific Name | Divergence (MYA) | Accession # | Seq Length (AA) | Seq ID % | Seq Sim % |
|---|---|---|---|---|---|---|
| Human | Homo sapiens | 0 | NP_001128144.1 | 233 | 100.0 | 100.0 |
| Aye-aye | Daubentonia madagascariensis | 74 | KAL2769215.1 | 233 | 88.8 | 94.0 |
| Mouse | Mus musculus | 87 | NP_001345202.1 | 236 | 78.8 | 88.6 |
| Echidna | Tachyglossus aculeatus | 180 | XP_038614343.1 | 235 | 62.3 | 76.3 |
| Rhea | Rhea pennata | 319 | XP_062436011.1 | 244 | 55.7 | 71.5 |
| Chicken | Gallus gallus | 319 | XP_004942371.2 | 244 | 55.1 | 69.2 |
| Zebrafish | Danio rerio | 429 | NP_001002536.1 | 256 | 44.2 | 61.7 |
| Lamprey | Petromyzon marinus | 563 | XP_032817389.1 | 227 | 35.1 | 50.0 |
| Lancelet | Branchiostoma floridae | 581 | XP_035676714.1 | 212 | 28.6 | 42.7 |
| Sea squirt | Styela clava | 596 | XP_039271579.1 | 169 | 21.6 | 36.4 |
| Trichoplax | Trichoplax sp. H2 | 661 | RDD41954.1 | 227 | 21.7 | 40.4 |
| Manila clam | Ruditapes philippinarum | 686 | XP_060572578.1 | 202 | 30.5 | 42.9 |
| Deer tick | Ixodes scapularis | 686 | XP_002435965.3 | 220 | 27.1 | 45.0 |
| Ribbon worm | Lineus longissimus | 686 | XP_064649596.1 | 210 | 26.5 | 46.6 |
| Horseshoe crab | Limulus polyphemus | 686 | XP_013773511.1 | 288 | 26.3 | 42.8 |
| Sea anemone | Nematostella vectensis | 715 | EDO37736.1 | 216 | 25.2 | 39.1 |
| Sponge | Corticium candelabrum | 758 | XP_062502458.1 | 245 | 29.7 | 44.9 |
| Fungus | Rhizophagus clarus | 1275 | GES81201.1 | 206 | 27.4 | 42.9 |
| Anaerobic gut fungus | Anaeromyces robustus | 1275 | ORX87713.1 | 192 | 25.2 | 41.9 |
RNA-seq and microarray studies indicate that FAM204A is ubiquitously but variably expressed at moderately high levels across human tissues, with higher transcript levels in cerebellum, kidney, prostate, thymus, thyroid, adipose tissue, and testis.[5]
High-throughput affinity capture–mass spectrometry (BioPlex) and yeast two-hybrid screens identify nuclear and chromatin-associated interactors of FAM204A. Reported partners include nuclear transport receptors (KPNA2, KPNA3, KPNB1),histone modifiers (H2AFJ,HAT1,KDM1A,SMYD1), andchaperones (HSP90AB1,DNAJC8).[19][20] These interactions suggest roles in nuclear import and chromatin regulation.
No Mendelian disorders are currently attributed to FAM204A.[21] However, its locus on 10q26.11 has been implicated in complex traits. A genome‑wide linkage and association study identified this region as associated with late‑onsetAlzheimer’s disease, although the signal may arise from FAM204A or neighboring genes within the locus.[22]
FAM204A is included in a U.S. patent (US 20140315736A1) disclosing blood‑based biomarker panels scored forAlzheimer's disease diagnosis, among which C10orf84/FAM204A is listed.[23]Variants in FAM204A also contribute to apolygenic "quit‑success" genotype score used to predict outcomes of smoking cessation therapy.[24]
Mouse knockout studies demonstrate that deletion of the Fam204a ortholog in mice results in pre‑weaning lethality, indicating that the gene may be essential for viability in mammals.[25]
