GABRG1

Chr 4

gamma-aminobutyric acid type A receptor subunit gamma1

NCBI Gene: 2565ENSG00000163285UniProt: Q8N1C3

The protein encoded by this gene belongs to the ligand-gated ionic channel family. It is an integral membrane protein and plays an important role in inhibiting neurotransmission by binding to the benzodiazepine receptor and opening an integral chloride channel. This gene is clustered with three other family members on chromosome 4. [provided by RefSeq, Jul 2008]

83
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GABRG1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 63 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.81LOEUF
pLI 0.000
Z-score 2.22
OE 0.48 (0.29–0.81)
Tolerant

Typical tolerance to LoF variation

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.
0.52Z-score
OE missense 0.91 (0.81–1.01)
220 obs / 242.8 exp
Tolerant

Mild missense constraint

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.0.48 (0.29–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.81–1.01)
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.1.20
0≤1.21.6
LoF obs/exp: 10 / 21.0Missense obs/exp: 220 / 242.8Syn Z: -1.46

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS63
Likely Benign1
18
Pathogenic
1
Likely Pathogenic
63
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
58
5
0
63
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total05824183

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRG1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GABRG1-related epileptic encephalopathy

limited
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GABRG1 variant as a potential novel cause of epileptic encephalopathy, hypotonia, and global developmental delay.
Williams A et al.·Am J Med Genet A
2022Case report
Epilepsy associated with autism and attention deficit hyperactivity disorder: is there a genetic link?
Lo-Castro A et al.·Brain Dev
2014Review
Interpopulation linkage disequilibrium patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4.
Ittiwut C et al.·Genomics
2008
Exploring Neuronal Vulnerability to Head Trauma Using a Whole Exome Approach.
Ibrahim O et al.·J Neurotrauma
2020
Effects of Common and Rare Chromosome 4 GABAergic Gene Variation on Alcohol Use and Antisocial Behavior.
Deak JD et al.·J Stud Alcohol Drugs
2019
GABA(A) subunit single nucleotide polymorphisms show sex-specific association to alcohol consumption and mental distress in a Norwegian population-based sample.
Moe JS et al.·Psychiatry Res
2022
A novel variant in GABRB2 associated with intellectual disability and epilepsy.
Srivastava S et al.·Am J Med Genet A
2014
Neurotrophic tyrosine receptor kinase gene fusions in adult and pediatric patients with solid tumors: a clinicogenomic biobank and record linkage study of expression frequency and patient characteristics from Finland.
Zhang W et al.·Acta Oncol
2024Cohort
A GABRA2 variant is associated with increased stimulation and 'high' following alcohol administration.
Arias AJ et al.·Alcohol Alcohol
2014
Genetic association of recovery from eating disorders: the role of GABA receptor SNPs.
Bloss CS et al.·Neuropsychopharmacology
2011
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