ARHGEF2

Chr 1

Rho/Rac guanine nucleotide exchange factor 2

Also known as: GEF, GEF-H1, GEFH1, LFP40, Lfc, NEDMHM, P40

NCBI Gene: 9181 ENSG00000116584 UniProt: Q92974

ARHGEF2 encodes a guanine nucleotide exchange factor that activates Rho-GTPases by promoting GDP-to-GTP exchange, playing critical roles in cell motility, neuronal development, and innate immune signaling. Autosomal recessive mutations cause neurodevelopmental disorder with midbrain and hindbrain malformations. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.156), indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, OMIM, UniProt

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate rho-dependent signals. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with midbrain and hindbrain malformations

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

0.16

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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