Palmoplantar keratoderma and erythrokeratodermas

Gene: GJB4

Green List (high evidence)

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

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.

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, 617524
OMIM
605425
Clinvar variants
Variants in GJB4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

15 Aug 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for GJB4 were set to Erythrokeratodermia variabilis et progressiva 2, 617524

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.

3 Apr 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).

16 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).

16 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).

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).

10 Jan 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for GJB4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

5 Jan 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for GJB4 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

5 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

GJB4 was created by rfoulger

5 Jan 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

GJB4 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Sources: Radboud University Medical Center, Nijmegen