FAF1

Chr 1

Fas associated factor 1

Also known as: CGI-03, HFAF1s, UBXD12, UBXN3A, hFAF1

NCBI Gene: 11124ENSG00000185104UniProt: Q9UNN5

Interaction of Fas ligand (TNFSF6) with the FAS antigen (TNFRSF6) mediates programmed cell death, also called apoptosis, in a number of organ systems. The protein encoded by this gene binds to FAS antigen and can initiate apoptosis or enhance apoptosis initiated through FAS antigen. Initiation of apoptosis by the protein encoded by this gene requires a ubiquitin-like domain but not the FAS-binding domain. [provided by RefSeq, Jul 2008]

87
ClinVar variants
7
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FAF1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 77 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.25LOEUF
pLI 0.999
Z-score 5.29
OE 0.12 (0.06–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.13Z-score
OE missense 0.68 (0.62–0.76)
246 obs / 359.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.06–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.62–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 5 / 41.9Missense obs/exp: 246 / 359.5Syn Z: 1.27

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS77
Likely Benign2
Benign1
4
Pathogenic
3
Likely Pathogenic
77
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
3
0
3
VUS
0
62
15
0
77
Likely Benign
0
0
0
2
2
Benign
0
0
1
0
1
Total06223287

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FAF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High Expression of Fas-Associated Factor 1 Indicates a Poor Prognosis in Non-Small-Cell Lung Cancer.
Hu D et al.·Curr Oncol
2023
Germline Mutations in FAF1 Are Associated With Hereditary Colorectal Cancer.
Bonjoch L et al.·Gastroenterology
2020
FAF1 Gene Involvement in Pituitary Corticotroph Tumors.
Nguyen M et al.·Horm Metab Res
2024
Association analysis of SNPs in GRHL3, FAF1, and KCNJ2 with NSCPO sub-phenotypes in Han Chinese.
Sun JL et al.·Oral Dis
2022
FAF1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis.
Xie F et al.·Nat Commun
2017
Mystery machine: the complex roles of NLRX1 in viral infection.
Woolls MK et al.·Front Immunol
2025Review
Inhibition of circ_0073932 attenuates myocardial ischemia‒reperfusion injury via miR-493-3p/FAF1/JNK.
Su Y et al.·In Vitro Cell Dev Biol Anim
2024
Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complex.
Ryu SW et al.·J Biol Chem
2003
FAF1, a gene that is disrupted in cleft palate and has conserved function in zebrafish.
Ghassibe-Sabbagh M et al.·Am J Hum Genet
2011Functional
Pharmacological Intervention Targeting FAF1 Restores Autophagic Flux for α-Synuclein Degradation in the Brain of a Parkinson's Disease Mouse Model.
Kim BS et al.·ACS Chem Neurosci
2022Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools