EPHB4
Chr 7ADEPH receptor B4
Also known as: CMAVM2, HFASD, HTK, LMPHM7, MYK1, TYRO11
EPHB4 encodes a receptor tyrosine kinase that binds ephrin-B ligands and controls cellular repulsion, segregation, and migration, playing a central role in vascular development and angiogenesis. Mutations cause autosomal dominant capillary malformation-arteriovenous malformation and lymphatic malformation, affecting vascular and lymphatic system development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.422), and these vascular malformations can present from infancy through childhood.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
EPHB4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools