Palmoplantar keratoderma and erythrokeratodermas
Gene: GJB4

GJB4 (gap junction protein beta 4)
EnsemblGeneIds (GRCh38): ENSG00000189433
EnsemblGeneIds (GRCh37): ENSG00000189433
OMIM: 605425, Gene2Phenotype
GJB4 is in 5 panels

2 reviews

Edel O'Toole (Queen Mary University of London)

Green List (high evidence)

Lots of literature on GJB4 as a causative gene in EKV
Created: 14 Mar 2017, 7:17 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Erythrokeratoderma variabilis

Created: 14 Mar 2017, 7:17 p.m.

Panel version: 0.135

Rebecca Foulger (Genomics England curator)

Comment on phenotypes: Removed 'Erythrokeratodermia variabilis with erythema gyratum repens,133200' as a phenotype since a June 2017 OMIM update now associates GJB4 with 'Erythrokeratodermia variabilis et progressiva 2, 617524'.
Created: 15 Aug 2017, 2:19 p.m.

Comment when marking as ready: Discussed with Helen Brittain, who agrees with Green rating and monoallelic MOI (cases reported for GJB4 are heterozygous).
Created: 3 Apr 2017, 9:12 a.m.

Comment on list classification: Updated rating from Amber to green: 1 green review plus >3 cases supporting causation for 'Erythrokeratodermia variabilis et progressiva'.
Created: 16 Mar 2017, 4:29 p.m.

Although GJB4 is not a confirmed DD gene for EKVP (OMIM:133200) >3 GJB4 cases listed in OMIM for 'Erythrokeratodermia variabilis et progressiva (OMIM:133200)' and plenty of literature recording GJB4 causative variants for OMIM:133200.
Created: 16 Mar 2017, 4:07 p.m.

Comment on list classification: Updated rating from Red to Amber ready for External review: >3 cases linking GJB4 to EKVP (OMIM:133200).
Created: 10 Jan 2017, 3:39 p.m.

Comment on mode of inheritance: Updated mode of inheritance from 'Both monoallelic and biallelic' to just monoallelic. Although OMIM report both biallelic and monoallelic causes of EKVP (OMIM:133200) for GJA1, GJB3 and GJB4, for GJB4 the literature reports heterozygous (monoallelic) mutations. Rare biallelic forms of EKVP (OMIM:133200) have so far just been reported for GJB3.
Created: 10 Jan 2017, 3:38 p.m.

Comment on mode of inheritance: Mode of inheritance sourced from OMIM: Both monoallelic and biallelic mutations in GJB4 are recorded for Erythrokeratodermia variabilis with erythema gyratum repens' (OMIM:133200).
Created: 5 Jan 2017, 1:20 p.m.

Created: 9 Jan 2017, 11:41 a.m.

Panel version: 0.65

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Radboud University Medical Center, Nijmegen

Phenotypes

Erythrokeratodermia variabilis et progressiva 2, OMIM:617524

OMIM

605425

Clinvar variants

Variants in GJB4

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

5 Apr 2022, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: GJB4 were changed from Erythrokeratodermia variabilis et progressiva 2, 617524 to Erythrokeratodermia variabilis et progressiva 2, OMIM:617524

15 Aug 2017, Gel status: 4