FAF2

Chr 5

Fas associated factor family member 2

Also known as: ETEA, UBXD8, UBXN3B

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
50
P/LP submissions
0%
P/LP missense
0.22
LOEUF· LoF intol.
Mechanism
Clinical SummaryFAF2
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
49 unique Pathogenic / Likely Pathogenic· 41 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.999
Z-score 4.66
OE 0.07 (0.030.22)
Highly constrained

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

Missense Constraint
2.52Z-score
OE missense 0.56 (0.490.64)
144 obs / 258.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.030.22)
00.351.4
Missense OE0.56 (0.490.64)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 2 / 29.2Missense obs/exp: 144 / 258.0Syn Z: 0.39

ClinVar Variant Classifications

115 submitted variants in ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic2
VUS41
Likely Benign1
47
Pathogenic
2
Likely Pathogenic
41
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
47
0
47
Likely Pathogenic
0
0
2
0
2
VUS
0
36
5
0
41
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total03655091

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

View in ClinVar →

Protein Context — Lollipop Plot

FAF2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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