ARHGAP4

Chr X

Rho GTPase activating protein 4

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

NCBI Gene: 393 ENSG00000089820 UniProt: P98171 OMIM: 300023

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.31

LOEUF· LoF intol.

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Mechanism