FAF1

Chr 1

Fas associated factor 1

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

NCBI Gene: 11124 ENSG00000185104 UniProt: Q9UNN5

The protein functions as a ubiquitin-binding protein that regulates DNA replication by targeting the replication licensing factor CDT1 for degradation and can potentiate FAS-induced apoptosis. Mutations cause neurodevelopmental disorder with progressive microcephaly, spasticity, and brain atrophy, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants in the general population.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOEUF 0.25

Clinical Summary— FAF1

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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.

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ClinVar Variants

63 VUS of 91 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.12 (0.06–0.25)

0≤0.351.4

Missense OE?0.68 (0.62–0.76)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 5 / 41.9Missense obs/exp: 246 / 359.5Syn Z: 1.27

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

VUS63

Likely Benign2

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	63	0	0	63
Likely Benign	0	0	2	2
Benign	0	1	0	1
Total	63	1	2	66

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap FAF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →