Cerebral vascular malformations

Gene: EPHB4

Amber List (moderate evidence)

EPHB4 (EPH receptor B4)
EnsemblGeneIds (GRCh38): ENSG00000196411
EnsemblGeneIds (GRCh37): ENSG00000196411
OMIM: 600011, Gene2Phenotype
EPHB4 is in 9 panels

2 reviews

Alexandra Njegic (Leeds Teaching Hospital Trust)

Green List (high evidence)

37978175 and 30578106: 5/114 probands with VOGM with EPHB4 variants. All variants transmitted, phenotype absent or milder in the parent carriers, suggests incomplete penetrance and variable expressivity. In vitro modelling of R838W, K650N and F867L in COS-7 (PMID 37978175) and HEK (PMID 30578106) cells showed reduced or absent protein tyrosine kinase activity of EPHB4.
29444212: Vein of Galen aneurysmal malformation, 5/51 patients with EPHB4 variant (only 2 had cutaneous CMs as an associated phenotype); 4 transmitted, suggests wide clinical spectrum. In vivo zebrafish ephb4a morphants show vascular abnormalities, rescuable by WT EPHB4 mRNA but not with an EPHB4 frameshift mimic mRNA.
39367533: 59 participants with CV-AVM, 1 patient with a brain AVM had an EPHB4 and an ACVRL1 variant.
35852613: Case report of an EPHB4 germline variant in patient with sporadic cavernous malformation.
Created: 8 Apr 2025, 9 a.m. | Last Modified: 8 Apr 2025, 9 a.m.
Panel Version: 3.18

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Capillary malformation-arteriovenous malformation 2, 618196

Publications

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: New Amber gene - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations
Created: 29 Nov 2019, 3:44 p.m. | Last Modified: 29 Nov 2019, 3:44 p.m.
Panel Version: 1.60
New gene rated Amber - deemed relevant to the GMS panel R336 Cerebral vascular malformations
Created: 29 Nov 2019, 3:43 p.m. | Last Modified: 29 Nov 2019, 3:43 p.m.
Panel Version: 1.59
Review from clinical expert (Vijeya Ganesan: GOSH / ICH): consider for this panel. GEL clinical team (Helen Brittain) Review of PMID 28687708 suggests that 3/110 patients had CNS lesions - therefore rated as amber pending further evidence
Sources: Expert list
Created: 29 Nov 2019, 3:43 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Capillary malformation-arteriovenous malformation 2, 618196

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Yorkshire and North East GLH
  • NHS GMS
  • Expert Review Amber
  • Expert list
Phenotypes
  • Capillary malformation-arteriovenous malformation 2, OMIM:618196
OMIM
600011
Clinvar variants
Variants in EPHB4
Penetrance
None
Panels with this gene

History Filter Activity

25 Mar 2021, Gel status: 2

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2, 618196 to Capillary malformation-arteriovenous malformation 2, OMIM:618196

29 Nov 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to EPHB4.

29 Nov 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to EPHB4.

29 Nov 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ephb4 has been classified as Amber List (Moderate Evidence).

29 Nov 2019, Gel status: 1

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

Louise Daugherty (Genomics England Curator)

gene: EPHB4 was added gene: EPHB4 was added to Cerebral vascular malformations. Sources: Expert list Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2, 618196 Review for gene: EPHB4 was set to AMBER