ClinGen Dosage Sensitivity Curation Page

GJB6

  • Curation Status: Complete

Location Information

Select assembly: (NC_000013.10) (NC_000013.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Mutations in GJB6 have been associated with nonsyndromic hearing loss (both autosomal recessive, autosomal dominant, and digenic inheritance with mutations in GJB2), as well as Clouston syndrome (autosomal dominant). Autosomal recessive nonsyndromic hearing loss (DFNB1): A recurrent ~342kb deletion of GJB6 has been noted amongst individuals with phenotypes consistent with DFNB1 (PMID: 11807148). This deletion has been seen in individuals of Spanish, French, and Israeli ancestry (OMIM 604418). Affected individuals have either been homozygous for the deletion, compound heterozygotes for other GJB6 mutations, or heterozygous for a GJB2 mutation. See GeneReviews for more information: http://www.ncbi.nlm.nih.gov/books/NBK1272/ Autosomal dominant nonsyndromic hearing loss (DFNA3B): At this time, only two variants in GJB6 have been reported as pathogenic for autosomal dominant nonsyndromic hearing loss - p.Thr5Met and p.Ala40Val (Grifa et al. 1999, Yang et al. 2007). These are believed to act in a dominant negative manner (PMID: 10471490). See GeneReviews for more information: http://www.ncbi.nlm.nih.gov/books/NBK1536/ Clouston syndrome: Four missense changes in GJB6 have been reported in association with Clouston syndrome, an autosomal dominant hidrotic ectodermal dysplasia syndrome. These changes are believed to cause this phenotype through a gain-of-function phenotype (PMID: 15213106). See GeneReviews for more information: http://www.ncbi.nlm.nih.gov/books/NBK1200/

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity