GABRG3
Chr 15gamma-aminobutyric acid type A receptor subunit gamma3
The GABRG3 protein is a gamma subunit of GABA-A receptors, pentameric ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain and contain the benzodiazepine binding site. Mutations cause autosomal recessive epileptic encephalopathy with intellectual disability and developmental delays. This gene is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.39), indicating that such mutations are likely to have significant clinical consequences.
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
373 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 296 | 1 | 297 |
Likely Pathogenic | 0 | 0 | 8 | 0 | 8 |
VUS | 1 | 37 | 12 | 1 | 51 |
Likely Benign | 0 | 4 | 0 | 0 | 4 |
Benign | 0 | 0 | 1 | 3 | 4 |
| Total | 1 | 41 | 317 | 5 | 364 |
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.
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