SH3BP4

Chr 2

SH3 domain binding protein 4

Also known as: BOG25, TTP

NCBI Gene: 23677 ENSG00000130147 UniProt: Q9P0V3

This protein regulates clathrin-mediated endocytosis of transferrin receptors and acts as a negative regulator of mTOR signaling by preventing Rag GTPase complex activation, thereby controlling cell growth, proliferation, and autophagy. Mutations cause autosomal recessive neurodevelopmental disorder with progressive microcephaly, seizures, and brain atrophy. The gene shows tolerance to loss-of-function variants (low pLI score), consistent with the recessive inheritance pattern observed clinically.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein with 3 Asn-Pro-Phe (NPF) motifs, an SH3 domain, a PXXP motif, a bipartite nuclear targeting signal, and a tyrosine phosphorylation site. This protein is involved in cargo-specific control of clathrin-mediated endocytosis, specifically controlling the internalization of a specific protein receptor. [provided by RefSeq, Jul 2008]

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)

—

P/LP submissions

—

P/LP missense

0.57

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429