ARHGAP4

Chr X

Rho GTPase activating protein 4

Also known as: C1, RGC1, RhoGAP4, SrGAP4, p115

The protein functions as a GTPase-activating protein that regulates Rho family GTPases, particularly inhibiting stress fiber organization and may down-regulate Rho-like GTPases in hematopoietic cells. Genomic deletions involving this gene have been identified in patients with nephrogenic diabetes insipidus, though the specific contribution of ARHGAP4 to this phenotype requires further clarification. This gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.31), suggesting intolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.31
Clinical SummaryARHGAP4
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). 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
0.31LOEUF
pLI 0.977
Z-score 4.57
OE 0.15 (0.080.31)
Highly constrained

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

Missense Constraint
0.69Z-score
OE missense 0.91 (0.830.99)
394 obs / 434.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.080.31)
00.351.4
Missense OE0.91 (0.830.99)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 5 / 33.6Missense obs/exp: 394 / 434.3Syn Z: -2.33

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARHGAP4 · 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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