INSIG1

Chr 7

insulin induced gene 1

Also known as: CL6

NCBI Gene: 3638 ENSG00000186480 UniProt: O15503

The encoded protein is an endoplasmic reticulum membrane protein that regulates cholesterol synthesis by controlling the transport and degradation of key cholesterol regulatory proteins including SCAP and HMG-CoA reductase. INSIG1 mutations cause autosomal dominant familial hypercholesterolemia, resulting in elevated cholesterol levels and increased cardiovascular risk. This gene shows low constraint against loss-of-function variants (pLI 0.001, LOEUF 1.12), suggesting tolerance to complete protein loss.

ResearchSummary from RefSeq, UniProt

This gene encodes an endoplasmic reticulum membrane protein that regulates cholesterol metabolism, lipogenesis, and glucose homeostasis. The encoded protein has six transmembrane helices which contain an effector protein binding site. It binds the sterol-sensing domains of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and is essential for the sterol-mediated trafficking of these two proteins. It promotes the endoplasmic reticulum retention of SCAP and the ubiquitin-mediated degradation of HMG-CoA reductase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.12

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

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