GJB6 (Gap junction beta-6 protein) variants and mutations

GJB6 (also known as Gap junction beta-6 protein) is a human protein-coding gene encoding a gap junction beta-6 protein. It forms connexin 30 gap junctions in the cochlea, skin, and other epithelia and contributes to intercellular ion and metabolite exchange. Deletions or pathogenic variants can cause nonsyndromic hearing loss or ectodermal dysplasia syndromes. This analysis covers 639 GJB6 variants and mutations. Of these, 93% have computational variant effect predictions. Disease context includes Clouston syndrome, autosomal recessive nonsyndromic hearing loss 1B, and autosomal dominant nonsyndromic hearing loss 3B. Example GJB6 variants include M1?, M1V, and D2N.

Variant analysis overview

Gene: GJB6
Protein: Gap junction beta-6 protein
UniProt accession: O95452
Organism: Homo sapiens
Variants analyzed: 639
Variant scope: all variants
Completed: 2026-08-21

Variant and mutation evidence

Variant composition: 347 unspecified-consequence records; 1 stop retained variant; 120 missense variants; 126 synonymous variants; 27 frameshift variants; 6 in-frame deletions; 2 in-frame insertions; 8 stop-gained variants; 3 substitution
Prediction scores: 592 variants have prediction scores (93% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Clouston syndrome, autosomal recessive nonsyndromic hearing loss 1B, autosomal dominant nonsyndromic hearing loss 3B, hearing loss, autosomal recessive, autosomal recessive nonsyndromic hearing loss 1A, X-linked hypohidrotic ectodermal dysplasia, neurodegenerative disease, X-linked mixed deafness with perilymphatic gusher, X-linked mixed hearing loss with perilymphatic gusher, autosomal dominant nonsyndromic hearing loss, KID syndrome, Palmoplantar hyperkeratosis.

Protein structure and variant hotspots

Protein features: 4 transmembrane segments.
Structural context: 233 variants have structural context.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable GJB6 variants

Examples include M1?, M1V, D2N, p.Asp2 Trp3insThrThrTyrGlnSerIle, D2D, D2A, W3*, G4G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

GJB6 analysis run — GJB6 (639 variants) — completed 2026-08-21