RAPGEF2

Chr 4

Rap guanine nucleotide exchange factor 2

Also known as: CNrasGEF, NRAPGEP, PDZ-GEF1, PDZGEF1, RA-GEF, RA-GEF-1, RAGEF, Rap-GEP

NCBI Gene: 9693 ENSG00000109756 UniProt: Q9Y4G8

RAPGEF2 encodes a guanine nucleotide exchange factor that activates Rap and Ras family GTPases by promoting GDP-to-GTP exchange, serving as a critical link in intracellular signaling cascades and playing essential roles in neuronal migration, axon outgrowth, and formation of major brain commissures during development. Mutations cause familial adult myoclonic epilepsy with autosomal dominant inheritance, typically presenting in adulthood. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.197), indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, OMIM, UniProt

Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF2, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000 [PubMed 10934204]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEpilepsy, familial adult myoclonic, 7

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)

—

P/LP submissions

—

P/LP missense

0.20

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429