Segmental overgrowth disorders - Deep sequencing

Gene: GJA4

Green List (high evidence)

GJA4 (gap junction protein alpha 4)
EnsemblGeneIds (GRCh38): ENSG00000187513
EnsemblGeneIds (GRCh37): ENSG00000187513
OMIM: 121012, Gene2Phenotype
GJA4 is in 2 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 4 Dec 2024, 5:08 p.m. | Last Modified: 4 Dec 2024, 5:08 p.m.
Panel Version: 3.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Tom Cullup (GOSH). There is sufficient evidence to promote this gene to green at the next GMS panel update.

A recurrent GJA4 c.121G>T (p.Gly41Cys) somatic variant has been found in >50 individuals with cavernous venous malformation. Functional studies have shown this is a GoF variant that leads to formation of a hyperactive hemichannel.
Created: 31 Jul 2023, 1:44 p.m. | Last Modified: 31 Jul 2023, 1:46 p.m.
Panel Version: 3.7

Tom Cullup (Great Ormond Street Hospital)

Green List (high evidence)

Multiple patients with shared phenotype and hot-spot Gly41Cys somatic gain of function mutation in 33912852.
Sources: Expert list
Created: 3 May 2023, 3:35 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cutaneous and hepatic vascular lesions (no OMIM phenotype)

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
  • Expert list
Phenotypes
  • Cutaneous and hepatic vascular lesions (no OMIM phenotype)
Tags
gene-checked recurrent-variant
OMIM
121012
Clinvar variants
Variants in GJA4
Penetrance
unknown
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

11 Dec 2024, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag gene-checked tag was added to gene: GJA4.

4 Dec 2024, Gel status: 3

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag recurrent-variant tag was added to gene: GJA4.

4 Dec 2024, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green was removed from gene: GJA4. Tag recurrent-variant was removed from gene: GJA4.

4 Dec 2024, Gel status: 3

Added New Source, Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to GJA4. Source Expert Review Green was added to GJA4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

31 Jul 2023, Gel status: 2

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_23_NHS_review was removed from gene: GJA4.

31 Jul 2023, Gel status: 2

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance, Set mode of pathogenicity

Arina Puzriakova (Genomics England Curator)

gene: GJA4 was added gene: GJA4 was added to Segmental overgrowth disorders - Deep sequencing. Sources: Expert Review Amber,Expert list Q3_23_promote_green, Q3_23_NHS_review, recurrent-variant tags were added to gene: GJA4. Mode of inheritance for gene: GJA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GJA4 were set to 33912852; 35642047; 35902510; 36209871; 37072338 Phenotypes for gene: GJA4 were set to Cutaneous and hepatic vascular lesions (no OMIM phenotype) Penetrance for gene: GJA4 were set to unknown Mode of pathogenicity for gene: GJA4 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments