ARHGAP6

Chr X

Rho GTPase activating protein 6

Also known as: RHOGAP6, RHOGAPX-1

NCBI Gene: 395ENSG00000047648UniProt: O43182OMIM: 300118

The protein functions as a GTPase-activating protein that inactivates Rho-type GTPases and regulates actin cytoskeleton dynamics during cell motility and morphological changes. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that functional copies are essential for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.23
Clinical Summary— ARHGAP6
⚡
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
50 unique Pathogenic / Likely Pathogenic· 127 VUS of 320 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.998
Z-score 4.52
OE 0.07 (0.03–0.23)
Highly constrained

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

Missense Constraint
1.82Z-score
OE missense 0.74 (0.67–0.81)
282 obs / 382.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.03–0.23)
0≤0.351.4
Missense OE0.74 (0.67–0.81)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 2 / 27.7Missense obs/exp: 282 / 382.3Syn Z: 0.64
DN
0.3693th %ile
GOF
0.4579th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 16% of P/LP variants are LoF · LOEUF 0.23

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

320 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic6
VUS127
Likely Benign13
44
Pathogenic
6
Likely Pathogenic
127
VUS
13
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
7
32
1
44
Likely Pathogenic
4
2
0
0
6
VUS
0
113
14
0
127
Likely Benign
0
3
2
8
13
Benign
0
0
0
0
0
Total8125489190

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

View in ClinVar →

Protein Context — Lollipop Plot

ARHGAP6 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients