ARHGAP31

Chr 3AD

Rho GTPase activating protein 31

Also known as: AOS, AOS1, CDGAP

The protein functions as a GTPase-activating protein that regulates RAC1 and CDC42, controlling cell spreading, lamellipodia formation, and cell migration. Mutations cause Adams-Oliver syndrome 1, characterized by congenital scalp defects and limb malformations, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI >0.99), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.191 OMIM phenotype
Clinical SummaryARHGAP31
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 6.23
OE 0.09 (0.050.19)
Highly constrained

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

Missense Constraint
0.80Z-score
OE missense 0.92 (0.860.98)
706 obs / 768.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.050.19)
00.351.4
Missense OE0.92 (0.860.98)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 5 / 54.8Missense obs/exp: 706 / 768.1Syn Z: 1.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongARHGAP31-related Adams-Oliver syndromeLOFAD
DN
0.4091th %ile
GOF
0.5465th %ile
LOF
0.71top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.19
GOF1 literature citation

Literature Evidence

GOFMutant transcripts are stable and increase ARHGAP31 activity in vitro through a gain-of-function mechanism.PMID:21565291

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARHGAP31 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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