SORBS2

Chr 4

sorbin and SH3 domain containing 2

Also known as: ARGBP2, PRO0618

NCBI Gene: 8470 ENSG00000154556 UniProt: O94875 OMIM: 616349

The SORBS2 protein functions as an adapter that assembles signaling complexes linking ABL kinases to the actin cytoskeleton and regulates pancreatic cell adhesion. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, suggesting that complete protein loss is not well tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. They interact with the Arg/Abl binding proteins via the SH3 domains present in the carboxy end of the latter group of proteins. This gene encodes the sorbin and SH3 domain containing 2 protein. It has three C-terminal SH3 domains and an N-terminal sorbin homology (SoHo) domain that interacts with lipid raft proteins. The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that it functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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)

—

P/LP submissions

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P/LP missense

0.40

LOEUF

Multiple*

Mechanism· predicted