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GJB3 – Autosomal Dominant Nonsyndromic Hearing Loss

Evidence for GJB3 (Cx31) contribution to autosomal dominant nonsyndromic hearing loss is limited and primarily derives from digenic inheritance with GJB2. In a study of 108 Chinese GJB2 heterozygotes, three unrelated families were identified in which compound heterozygosity for GJB2 pathogenic alleles and a GJB3 variant co-segregated with non-syndromic hearing impairment, including GJB3 c.497A>G (p.Asn166Ser) ([PMID:19050930]). Functional assays demonstrated that Cx31 and Cx26 co-assemble into heteromeric connexons in vitro, providing biological plausibility for a digenic mechanism in these families ([PMID:19050930]).

References

  • Human genetics • 2009 • Digenic inheritance of non-syndromic deafness caused by mutations at the gap junction proteins Cx26 and Cx31. PMID:19050930

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

3 unrelated families with compound heterozygous GJB2/GJB3 variants ([PMID:19050930])

Genetic Evidence

Limited

Identification of three digenic heterozygotes in unrelated pedigrees

Functional Evidence

Supporting

In vitro co-assembly of Cx31 and Cx26 supports digenic interaction ([PMID:19050930])