ARHGAP31

Chr 3AD

Rho GTPase activating protein 31

Also known as: AOS, AOS1, CDGAP

NCBI Gene: 57514ENSG00000031081UniProt: Q2M1Z3

This gene encodes a GTPase-activating protein (GAP). A variety of cellular processes are regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling between inactive and active forms is regulated by guanine nucleotide exchange factors and GAPs. The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Adams-Oliver syndrome 1MIM #100300
AD
570
ClinVar variants
17
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ARHGAP31
⚡
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
17 Pathogenic / Likely Pathogenic· 308 VUS of 570 total submissions
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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.
0.19LOEUF
pLI 1.000
Z-score 6.23
OE 0.09 (0.05–0.19)
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.
0.80Z-score
OE missense 0.92 (0.86–0.98)
706 obs / 768.1 exp
Tolerant

Mild missense constraint

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.0.09 (0.05–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.86–0.98)
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.0.93
0≤1.21.6
LoF obs/exp: 5 / 54.8Missense obs/exp: 706 / 768.1Syn Z: 1.00

ClinVar Variant Classifications

570 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS308
Likely Benign163
Benign58
Conflicting24
16
Pathogenic
1
Likely Pathogenic
308
VUS
163
Likely Benign
58
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
15
0
16
Likely Pathogenic
1
0
0
0
1
VUS
7
279
17
5
308
Likely Benign
0
32
49
82
163
Benign
0
7
40
11
58
Conflicting
—24
Total931812198570

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

View 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.

Gene2Phenotype Curations

ARHGAP31-related Adams-Oliver syndrome

strong
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkinSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Adams-Oliver syndrome 1

MIM #100300

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Characterization of a New Variant in ARHGAP31 Probably Involved in Adams-Oliver Syndrome in a Family with a Variable Phenotypic Spectrum.
Santaniello C et al.·Genes (Basel)
2024🔓 Open Access
A DLG1-ARHGAP31-CDC42 axis is essential for the intestinal stem cell response to fluctuating niche Wnt signaling.
Castillo-Azofeifa D et al.·Cell Stem Cell
2023
Synergistic effects of rare variants of ARHGAP31 and FBLN1 in vitro in terminal transverse limb defects.
Tian H et al.·Front Genet
2022🔓 Open Access
CdGAP/ARHGAP31 is regulated by RSK phosphorylation and binding to 14-3-3β adaptor protein.
Ben Djoudi Ouadda A et al.·Oncotarget
2018🔓 Open Access
CdGAP/ARHGAP31, a Cdc42/Rac1 GTPase regulator, is critical for vascular development and VEGF-mediated angiogenesis.
Caron C et al.·Sci Rep
2016🔓 Open Access
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