GABRA6

Chr 5

gamma-aminobutyric acid type A receptor subunit alpha6

NCBI Gene: 2559ENSG00000145863UniProt: Q16445

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. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]

113
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GABRA6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 58 VUS of 113 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.
1.38LOEUF
pLI 0.000
Z-score 0.25
OE 0.94 (0.65–1.38)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.41Z-score
OE missense 1.07 (0.97–1.19)
257 obs / 239.2 exp
Tolerant

Tolerant to missense variation

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.0.94 (0.65–1.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.97–1.19)
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: 19 / 20.2Missense obs/exp: 257 / 239.2Syn Z: -1.47

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS58
Likely Benign21
Benign12
19
Pathogenic
3
Likely Pathogenic
58
VUS
21
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
3
0
3
VUS
3
45
10
0
58
Likely Benign
0
8
3
10
21
Benign
0
3
2
7
12
Total3563717113

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

View in ClinVar →

Protein Context — Lollipop Plot

GABRA6 · 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
Rare variants in neuronal excitability genes influence risk for bipolar disorder.
Ament SA et al.·Proc Natl Acad Sci U S A
2015
A new stress sensor and risk factor for suicide: the T allele of the functional genetic variant in the GABRA6 gene.
Gonda X et al.·Sci Rep
2017Functional
Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population.
Kumari R et al.·Clin Chim Acta
2011
Association of gamma-aminobutyric acid A receptor α2 gene (GABRA2) with alcohol use disorder.
Li D et al.·Neuropsychopharmacology
2014Meta-analysis
A novel antisense lncRNA, ARBAG harboring an RNA destabilizing GWAS variant for C-peptide dictates the transcript isoforms of GABRA6 in cerebellum.
Bandesh K et al.·Hum Mol Genet
2023
Sex differences in GABA(A) receptor subunit transcript expression are mediated by genotype in subjects with alcohol-related cirrhosis of the liver.
Ashton MK et al.·Genes Brain Behav
2022
Canavan disease: a monogenic trait with complex genomic interaction.
Surendran S et al.·Mol Genet Metab
2003Review
Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort.
Rochtus A et al.·Epilepsia
2020Cohort
Predictive Role of Cluster Bean (Cyamopsis tetragonoloba) Derived miRNAs in Human and Cattle Health.
Sahu S et al.·Genes (Basel)
2024
A novel variant in GABRB2 associated with intellectual disability and epilepsy.
Srivastava S et al.·Am J Med Genet A
2014
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