GABRA4
Chr 4gamma-aminobutyric acid type A receptor subunit alpha4
The GABRA4 protein forms the alpha-4 subunit of GABA-A receptors, heteropentameric chloride channels that mediate inhibitory neurotransmission in the brain, with alpha-4-containing receptors predominantly located extrasynaptically where they provide tonic inhibition. Mutations in GABRA4 have been associated with autism spectrum disorders, following autosomal dominant inheritance. The gene shows high constraint against loss-of-function variants (LOEUF 0.41), indicating that such variants are likely to be pathogenic when they occur.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
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
GABRA4 · 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