Palmoplantar keratoderma and erythrokeratodermas

Gene: GJB3

Green List (high evidence)

GJB3 (gap junction protein beta 3)
EnsemblGeneIds (GRCh38): ENSG00000188910
EnsemblGeneIds (GRCh37): ENSG00000188910
OMIM: 603324, Gene2Phenotype
GJB3 is in 11 panels

2 reviews

Edel O'Toole (Queen Mary University of London)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Erythrokeratoderma; deafness; peripheral neuropathy

Publications

Mode of pathogenicity
Other

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Amber to Green: Although the reviewer did not leave a rating for GJB3, other comments were left suggesting that it is a suitable gene for the panel. >3 unrelated cases to support causation of relevant phenotype.
Created: 23 Mar 2017, 10:32 a.m.
Comment on list classification: Updated rating from Red to Amber ready for External review. Confirmed DD gene, and >3 cases of GJB3 variants linked to EKVP (OMIM:133200).
Created: 10 Jan 2017, 3:36 p.m.
Comment on mode of inheritance: Mode of inheritance sourced from OMIM: both monoallelic and biallelic mutations in GJB3 are recorded for 'Erythrokeratodermia variabilis et progressiva' (OMIM:133200). Biallelic (AR) mutations are reported in Gottfried et al., 2002 (PMID:12019212) and Fuchs-Telem et al, 2011 (PMID:21564177).
Created: 9 Jan 2017, 11:45 a.m.
Comment on publications: PMID:21564177 reports an autosomal recessive GJB3 mutation (c.G88A leading to a V30I substitution) causing Erythrokeratoderma variabilis (EKVP).
Created: 9 Jan 2017, 11:44 a.m.
GJB3 is a confirmed DD gene for 'Erythrokeratodermia variabilis et progressiva' (OMIM:133200).
Created: 9 Jan 2017, 11:30 a.m.
Gottfried et al. (2002, PMID:12019212) identified 3 Israeli siblings with an autosomal recessive (AR) migratory form of erythrokeratodermia variabilis et progressiva (EKVP; 133200) who were homozygous for a 101T-C transition in GJB3.
Created: 9 Jan 2017, 11:29 a.m.
Wigloss et al., (1999, PMID: 10594760) identified an R42P mutation in the GJB3 gene in a family with EKVP (OMIM:133200). Richard et al., 2000 (PMID:10798362) found the same heterozygous mutation as the cause of EKV in another family.
Created: 9 Jan 2017, 11:28 a.m.
Richard et al., (1998, PMID:9843209) identified heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D), or change of a cysteine (C86S).
Created: 9 Jan 2017, 11:27 a.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Other
Phenotypes
  • Erythrokeratodermia variabilis et progressiva, 133200
  • Erythrokeratodermia Variabilis
  • Erythrokeratoderma
  • deafness
  • peripheral neuropathy
OMIM
603324
Clinvar variants
Variants in GJB3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

11 Apr 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

Promoted to Version 1, April 11th 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.

23 Mar 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

23 Mar 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

23 Mar 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for GJB3 were set to Erythrokeratodermia variabilis et progressiva, 133200; Erythrokeratodermia Variabilis; Erythrokeratoderma; deafness; peripheral neuropathy

23 Mar 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for GJB3 were set to 21564177; 12019212; 9843209; 10594760

10 Jan 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

9 Jan 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for GJB3 were set to 21564177

5 Jan 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for GJB3 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

5 Jan 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

GJB3 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Source: Radboud University Medical Center, Nijmegen

5 Jan 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

GJB3 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Sources: Other

5 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

GJB3 was created by rfoulger