FAF2

Chr 5

Fas associated factor family member 2

Also known as: ETEA, UBXD8, UBXN3B

NCBI Gene: 23197 ENSG00000113194 UniProt: Q96CS3 OMIM: 616935

The FAF2 protein mediates endoplasmic reticulum-associated degradation of misfolded proteins, regulates insulin-like growth factor receptor signaling, inhibits lipid droplet degradation, and promotes stress granule disassembly. Mutations cause autosomal recessive neurodevelopmental disorder with progressive microcephaly, seizures, and brain atrophy. This gene is highly constrained against loss-of-function variants, indicating that such mutations are typically pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is highly expressed in peripheral blood of patients with atopic dermatitis (AD), compared to normal individuals. It may play a role in regulating the resistance to apoptosis that is observed in T cells and eosinophils of AD patients. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.22

Clinical Summary— FAF2

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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

36 VUS of 61 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 0.999

Z-score 4.66

OE 0.07 (0.03–0.22)

Highly constrained

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

Missense Constraint?

2.52Z-score

OE missense 0.56 (0.49–0.64)

144 obs / 258.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.22)

0≤0.351.4

Missense OE?0.56 (0.49–0.64)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 2 / 29.2Missense obs/exp: 144 / 258.0Syn Z: 0.39

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS36

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	36	0	36
Likely Benign	0	1	1
Benign	0	0	0
Total	36	1	37

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

View in ClinVar →

51 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap FAF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →