GABRG3

Chr 15

gamma-aminobutyric acid type A receptor subunit gamma3

This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.39
Clinical SummaryGABRG3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
1 unique Pathogenic / Likely Pathogenic· 39 VUS of 57 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.39LOEUF
pLI 0.847
Z-score 3.76
OE 0.17 (0.080.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.52Z-score
OE missense 0.56 (0.490.64)
145 obs / 259.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.17 (0.080.39)
00.351.4
Missense OE?0.56 (0.490.64)
00.61.4
Synonymous OE?1.02
01.21.6
LoF obs/exp: 4 / 23.8Missense obs/exp: 145 / 259.1Syn Z: -0.17

This gene — mechanism propensity

DN
0.6840th %ile
GOF
0.72top 25%
LOF
0.4135th %ile

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

GOFprediction above median
DNprediction 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

57 submitted variants in ClinVar

Classification Summary

Pathogenic1
VUS39
Likely Benign4
Benign4
1
Pathogenic
39
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
1
1
Likely Pathogenic
0
0
0
0
0
VUS
1
37
0
1
39
Likely Benign
0
4
0
0
4
Benign
0
0
1
3
4
Total1411548

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

View in ClinVar →

305 pathogenic / likely-pathogenic (of 317) ClinVar copy-number / structural variants overlap GABRG3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

GABRG3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →