RGS14

Chr 5

regulator of G protein signaling 14

NCBI Gene: 10636 ENSG00000169220 UniProt: O43566 OMIM: 602513

This protein regulates G protein-coupled receptor signaling by acting as a GTPase activating protein and GDP-dissociation inhibitor, terminating G protein signals and modulating cellular processes including neurite outgrowth and learning/memory. Mutations cause autosomal recessive spinocerebellar ataxia with developmental delay and intellectual disability, typically presenting in childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.58), affecting primarily neurological and cerebellar systems.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [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)

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P/LP submissions

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P/LP missense

0.58

LOEUF

Multiple*

Mechanism· predicted