GET3

Chr 19AR

guided entry of tail-anchored proteins factor 3, ATPase

Also known as: ARSA-I, ARSA1, ASNA-I, ASNA1, CMD2H, TRC40

NCBI Gene: 439 ENSG00000198356 UniProt: O43681 OMIM: 601913

The GET3 protein functions as an ATPase that delivers tail-anchored proteins from the cytosol to the endoplasmic reticulum by recognizing their transmembrane domains and facilitating their membrane insertion through ATP-dependent conformational changes. Biallelic mutations cause autosomal recessive dilated cardiomyopathy, though the complete phenotypic spectrum remains to be fully defined. The gene shows high constraint against loss-of-function variants, suggesting mutations predominantly cause disease through loss of function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene represents the human homolog of the bacterial arsA gene, encoding the arsenite-stimulated ATPase component of the arsenite transporter responsible for resistance to arsenicals. This protein is also a central component of a transmembrane domain (TMD) recognition complex (TRC) that is involved in the post-translational delivery of tail-anchored (TA) proteins from the cytosol to the endoplasmic reticulum (ER). It recognizes and selectively binds the TMD of TA proteins in the cytosol, and delivers them to the ER for insertion. [provided by RefSeq, Oct 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Cardiomyopathy, dilated, 2HMIM #620203

Clinical highlights

Gene-disease validity (ClinGen)

cardiomyopathy, dilated, 2H · ARLimitednot for standalone diagnostic reporting

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

0.35

LOEUF

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Mechanism