GABRG3

Chr 15

gamma-aminobutyric acid type A receptor subunit gamma3

NCBI Gene: 2567ENSG00000182256UniProt: Q99928

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]

360
ClinVar variants
302
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— GABRG3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
302 Pathogenic / Likely Pathogenic· 50 VUS of 360 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.39LOEUF
pLI 0.847
Z-score 3.76
OE 0.17 (0.08–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.52Z-score
OE missense 0.56 (0.49–0.64)
145 obs / 259.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.08–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.56 (0.49–0.64)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 4 / 23.8Missense obs/exp: 145 / 259.1Syn Z: -0.17

ClinVar Variant Classifications

360 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic295
Likely Pathogenic7
VUS50
Likely Benign4
Benign4
295
Pathogenic
7
Likely Pathogenic
50
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
294
1
295
Likely Pathogenic
0
0
7
0
7
VUS
1
36
12
1
50
Likely Benign
0
4
0
0
4
Benign
0
0
1
3
4
Total1403145360

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRG3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding the clinico-molecular spectrum of Angelman syndrome phenotype with the GABRG3 gene: Evidence from methylation and sequencing studies.
Iyer GR et al.·Ann Hum Genet
2022
Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders.
Ranieri A et al.·Genes (Basel)
2024Cohort
Association of GABRG3, GABRB3, HTR2A gene variants with autism spectrum disorder.
Coskunpinar EM et al.·Gene
2023
SNP-PCR genotyping links alterations in the GABAA receptor (GABRG3: rs208129) and RELN (rs73670) genes to autism spectrum disorder among peadiatric Iraqi Arabs.
Ali ZA et al.·Mol Biol Rep
2022
Genetic Determinants for Leisure-Time Physical Activity.
Lin X et al.·Med Sci Sports Exerc
2018
Atypical absence seizures and gene variants: A gene-based review of etiology, electro-clinical features, and associated epilepsy syndrome.
Zhao X et al.·Epilepsy Behav
2024Review
Association study and mutation sequencing of genes on chromosome 15q11-q13 identified GABRG3 as a susceptibility gene for autism in Chinese Han population.
Wang L et al.·Transl Psychiatry
2018
An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population.
Hou SJ et al.·BMC Med Genomics
2021
Characterization of breakpoints in the GABRG3 and TSPY genes in a family with a t(Y;15)(p11.2;q12).
Gole L et al.·Am J Med Genet A
2004Case report
Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes.
Frohlich J et al.·Biol Psychiatry
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools