GABRR3

Chr 3

gamma-aminobutyric acid type A receptor subunit rho3

NCBI Gene: 200959 ENSG00000183185 UniProt: A8MPY1 OMIM: 618668

The GABRR3 protein forms the rho subunit of pentameric GABA(C) receptors, which are ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain by allowing chloride flow when activated by GABA. A common polymorphism (rs832032) is predicted to inactivate the gene product in some individuals, though specific disease associations with GABRR3 mutations are not established in the current literature.

OMIM ResearchSummary from RefSeq, UniProt

The neurotransmitter gamma-aminobutyric acid (GABA) functions in the central nervous system to regulate synaptic transmission of neurons. This gene encodes one of three related subunits, which combine as homo- or hetero-pentamers to form GABA(C) receptors. In humans, some individuals contain a single-base polymorphism (dbSNP rs832032) that is predicted to inactivate the gene product. [provided by RefSeq, Jan 2012]

OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— GABRR3

📋

ClinVar Variants

83 VUS of 97 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.80top 25%

GOF

0.77top 25%

LOF

0.3453th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

VUS83

Likely Benign7

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	83	83
Likely Benign	7	7
Benign	0	0
Total	90	90

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap GABRR3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →