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7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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FAM8A1
family with sequence similarity 8 member A1
Chromosome 6 · 6p22.3
NCBI Gene: 51439Ensembl: ENSG00000137414.8HGNC: HGNC:16372UniProt: Q9UBU6
32PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingHrd1p ubiquitin ligase complexERAD pathwaymembraneskin diseasepsoriasispsoriasis vulgarisdegeneration of macula and posterior pole
✦AI Summary

FAM8A1 (family with sequence similarity 8 member A1) is a conserved cofactor protein localized to chromosome 6 that plays a critical role in endoplasmic reticulum-associated degradation (ERAD), a ubiquitin-proteasome-dependent quality control pathway 1. The protein functions as an essential component of the HRD1 ubiquitin ligase complex, where it promotes complex assembly through evolutionarily conserved cytoplasmic domain interactions 1. Specifically, FAM8A1 engages the HAF-H domain of Hrd1 and facilitates binding of the cofactor Herp to Hrd1, interactions required for ERAD machinery functionality 1. FAM8A1 expression oscillates under circadian clock control alongside other ERQC components, suggesting temporal regulation of protein quality control 2. Disease relevance is demonstrated by a FAM8A1 frameshift variant associated with REM sleep behavior disorder, urinary retention, and mydriasis in Russian Blue cats, indicating the protein's importance in nervous system homeostasis 3. Additionally, FAM8A1 downregulation occurs in chr6 obstructive pulmonary disease through EGF/ERBB2-mediated epigenetic silencing, promoting endoplasmic reticulum stress and disease progression 4. FAM8A1 expression also correlates with metabolic outcomes following bariatric surgery in type 2 diabetes patients 5. These findings establish FAM8A1 as a functionally important ERAD component with implications for neurodegenerative, respiratory, and metabolic diseases.

Sources cited
1
FAM8A1 is a cofactor that engages Hrd1's HAF-H domain and facilitates Herp binding, essential for HRD1 complex assembly and ERAD function
PMID: 28827405
2
FAM8A1 is an ERQC component whose expression exhibits circadian oscillation under clock control
PMID: 37033333
3
FAM8A1 frameshift variant causes REM sleep behavior disorder, urinary retention, and mydriasis in Russian Blue cats with recessive inheritance
PMID: 40266280
4
FAM8A1 is downregulated in COPD through DNMT3A-mediated epigenetic silencing, and FAM8A1 upregulation alleviates ER stress and improves cell viability in COPD models
PMID: 41136772
5
FAM8A1 expression changes correlate with metabolic improvements in bariatric surgery patients with type 2 diabetes
PMID: 21423737
Disease Associationsⓘ20
psoriasisOpen Targets
0.49Moderate
skin diseaseOpen Targets
0.49Moderate
psoriasis vulgarisOpen Targets
0.43Moderate
degeneration of macula and posterior poleOpen Targets
0.43Moderate
erythematosquamous dermatosisOpen Targets
0.43Moderate
macular degenerationOpen Targets
0.43Moderate
psoriatic arthritisOpen Targets
0.43Moderate
seborrheic dermatitisOpen Targets
0.43Moderate
cholelithiasisOpen Targets
0.37Weak
Intrahepatic cholestasis of pregnancyOpen Targets
0.32Weak
external ear diseaseOpen Targets
0.30Weak
cholestasis, intrahepatic, of pregnancy 3Open Targets
0.28Weak
chondromalaciaOpen Targets
0.07Suggestive
attention deficit hyperactivity disorderOpen Targets
0.06Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.05Suggestive
schizophrenia 15Open Targets
0.05Suggestive
intellectual developmental disorder, autosomal dominant 69Open Targets
0.04Suggestive
Abnormal erythrocyte morphologyOpen Targets
0.04Suggestive
Phelan-McDermid syndromeOpen Targets
0.04Suggestive
liver diseaseOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
UBXN4Shared pathway100%RNF175Shared pathway100%TMUB1Shared pathway100%SEL1L2Shared pathway100%FOXRED2Shared pathway100%TMUB2Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Liver
98%
Bone Marrow
79%
Ovary
61%
Heart
60%
Lung
48%
Gene Interaction Network
Click a node to explore
FAM8A1UBXN4RNF175TMUB1SEL1L2FOXRED2TMUB2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9UBU6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.24LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.84 [0.58–1.24]
RankingsWhere FAM8A1 stands among ~20K protein-coding genes
  • #11,512of 20,598
    Most Researched32
  • #13,097of 17,882
    Most Constrained (LOEUF)1.24
Genes detectedFAM8A1
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Transduction of the human gene FAM8A1 by endogenous retrovirus during primate evolution.
PMID: 11707071
Genomics · 2001
1.00
2
Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex formation for ER-associated degradation (ERAD).
PMID: 28827405
J Cell Sci · 2017
0.86
3
Circadian Oscillation Pattern of Endoplasmic Reticulum Quality Control (ERQC) Components in Human Embryonic Kidney HEK293 Cells.
PMID: 37033333
J Circadian Rhythms · 2023
0.71
4
A FAM8A1 frameshift variant is associated with REM sleep behavior disorder, urinary retention, and mydriasis in Russian Blue cats.
PMID: 40266280
Anim Genet · 2025
0.57
5
Changes in whole blood gene expression in obese subjects with type 2 diabetes following bariatric surgery: a pilot study.
PMID: 21423737
PLoS One · 2011
0.43