GPR146

Chr 7

G protein-coupled receptor 146

Also known as: PGR8

NCBI Gene: 115330 ENSG00000164849 UniProt: Q96CH1

GPR146 encodes a G-protein coupled receptor that regulates plasma cholesterol levels by binding the gut hormone cholesin, which inhibits hepatic cholesterol synthesis in response to intestinal cholesterol absorption. Mutations cause autosomal recessive familial hypercholesterolemia, presenting with elevated cholesterol levels and increased cardiovascular risk. The gene shows tolerance to loss-of-function variants in the general population.

ResearchSummary from RefSeq, UniProt

Enables G protein-coupled receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and regulation of cholesterol biosynthetic process. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

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

1.06

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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