Ichthyosis and erythrokeratoderma

Gene: GJB2

Green List (high evidence)

GJB2 (gap junction protein beta 2)
EnsemblGeneIds (GRCh38): ENSG00000165474
EnsemblGeneIds (GRCh37): ENSG00000165474
OMIM: 121011, Gene2Phenotype
GJB2 is in 12 panels

2 reviews

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Green rating agreed by Helen Brittain: cases found from 3 unrelated families with AD deafness and PPK. Helen notes that is possible that the mutational spectrum may be limited (to date, the mutations affect codons 59, 73 and 75).
Created: 3 Apr 2017, 9:07 a.m.
Mode of inheritance is listed as monoallelic. Although biallelic GJB2 mutations have been reported with 'Deafness, autosomal recessive 1A (OMIM:220290)' OMIM:220290 does not present with keratodermas, and therefore the mode of inheritance is recorded only for GJB2 disorders relevant to this skin disorder panel.
Created: 10 Jan 2017, 2:15 p.m.
GJB2 is a confirmed DD gene for 'palmoplantar keratoderma with deafness' (OMIM:148350), amongst other disorders.
Created: 9 Jan 2017, 12:07 p.m.
3 GJB2 variants listed in OMIM for palmoplantar keratoderma with deafness (OMIM:148350): In a family with autosomal dominant deafness and palmoplantar keratoderma (OMIM:148350), Heathcote et al. (2000, PMID:10633135) identified a G-to-C transversion at nucleotide 175 of the GJB2 gene resulting in the substitution G59A. In a 4-generation Turkish family segregating for autosomal dominant deafness and palmoplantar keratoderma (148350), Uyguner et al. (2002, PMID:12372058) identified a 224G-A transition in the GJB2 gene resulting in an R75Q mutation. In a 40-year-old German woman and her 2 children with palmoplantar keratoderma and sensorineural deafness, de Zwart-Storm et al. (2008, PMID:17993581) identified heterozygosity for a mutation in the GJB2 gene (H73R).
Created: 9 Jan 2017, 12:05 p.m.
Comment on list classification: Updated rating from Red to Green because GJB2 is included in the Eligibility statement gene list for 'Prior genetic testing' for patients with Keratoderma with deafness.
Created: 9 Jan 2017, 11:56 a.m.


Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Expert Review Green
  • Hystrix-like ichthyosis with deafness, 602540
  • Keratoderma, palmoplantar, with deafness, 148350
  • Deafness, autosomal recessive 1A, 220290
  • Deafness, autosomal dominant 3A, 601544
  • Keratitis-ichthyosis-deafness syndrome, 148210
  • Vohwinkel syndrome, 124500
  • Keratoderma with deafness
  • Bart-Pumphrey syndrome, 149200
Clinvar variants
Variants in GJB2
Panels with this gene

History Filter Activity

3 Jan 2019, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: GJB2 was added gene: GJB2 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: GJB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: GJB2 were set to Hystrix-like ichthyosis with deafness, 602540; Keratoderma, palmoplantar, with deafness, 148350; Deafness, autosomal recessive 1A, 220290; Deafness, autosomal dominant 3A, 601544; Keratitis-ichthyosis-deafness syndrome, 148210; Vohwinkel syndrome, 124500; Keratoderma with deafness; Bart-Pumphrey syndrome, 149200