GABRA6
Chr 5gamma-aminobutyric acid type A receptor subunit alpha6
The GABRA6 protein is an alpha subunit of GABA-A receptors, heteropentameric ligand-gated chloride channels that mediate the major inhibitory neurotransmission in the brain and are found at both synaptic and extrasynaptic sites including glutamatergic synapses. Mutations in GABRA6 cause autosomal recessive early infantile epileptic encephalopathy with febrile seizures plus, characterized by seizure onset in infancy. This gene is not highly constrained against loss-of-function variation, which is consistent with the recessive inheritance pattern observed in associated disorders.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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.
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
0 submitted variants 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools