GJB3
Chr 1ADARDigenic dominantgap junction protein beta 3
The encoded protein forms connexons that create gap junction channels allowing diffusion of small molecules between adjacent cells. Mutations cause autosomal dominant or digenic hearing loss (sometimes with peripheral neuropathy) and erythrokeratodermia variabilis et progressiva, a progressive skin disorder with variable erythematous and hyperkeratotic patches. The gene shows low constraint to loss-of-function variants, and inheritance patterns include autosomal dominant, autosomal recessive, and digenic mechanisms.
Disputed — evidence questions this relationship
2 total gene-disease associations curated
Some data sources returned errors (1)
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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 (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. 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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GJB3 · 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
External Resources
Links to major genomics databases and tools