SH3RF1

Chr 4

SH3 domain containing ring finger 1

Also known as: POSH, RNF142, SH3MD2

NCBI Gene: 57630 ENSG00000154447 UniProt: Q7Z6J0

The protein functions as an E3 ubiquitin ligase involved in protein sorting at the trans-Golgi network and acts as a scaffold protein coordinating JNK signaling pathway components, playing a crucial role in neocortical neuron migration during brain development. Mutations cause autosomal recessive intellectual disability with neuronal migration defects. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.505), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein containing an N-terminus RING-finger, four SH3 domains, and a region implicated in binding of the Rho GTPase Rac. Via the RING-finger, the encoded protein has been shown to function as an ubiquitin-protein ligase involved in protein sorting at the trans-Golgi network. The encoded protein may also act as a scaffold for the c-Jun N-terminal kinase signaling pathway, facilitating the formation of a functional signaling module. [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)

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P/LP submissions

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P/LP missense

0.51

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

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