EPHB4
Ephrin type-B receptor 4: a key regulator of vascular development, angiogenesis, and tumor progression
Gene Information Card
| Symbol | EPHB4 |
|---|---|
| Full Name | EPH receptor B4 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 2050 ncbi.nlm.nih.gov/gene/2050 |
| Ensembl ID | ENSG00000196411 |
| UniProt ID | P54760 |
| OMIM ID | 600011 |
| HGNC ID | 3395 |
| Aliases | HTK, MYK1, TYRO11 |
Description
EPHB4 encodes a member of the ephrin receptor subfamily of receptor tyrosine kinases. It binds specifically to ephrin-B2 and plays a critical role in vascular development, angiogenesis, and cell migration. EPHB4 is involved in both embryonic and postnatal vascular remodeling and has been implicated in tumor angiogenesis and progression. Mutations in EPHB4 are associated with hereditary hemorrhagic telangiectasia type 2 (HHT2) and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary hemorrhagic telangiectasia type 2 (HHT2) | Loss-of-function mutations impair vascular development, leading to telangiectases and arteriovenous malformations. | ClinVar, OMIM |
| Prostate cancer | EPHB4 overexpression promotes tumor growth and angiogenesis via ephrin-B2 signaling. | COSMIC, NCBI |
| Breast cancer | EPHB4 expression correlates with poor prognosis and metastasis. | COSMIC, NCBI |
| Colorectal cancer | EPHB4 mutations and altered expression contribute to tumor progression. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Placenta | 15.2 | Medium |
| Lung | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Brain | 6.7 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 18.5 | High expression |
| MCF7 (breast cancer) | 9.8 | Medium expression |
| PC3 (prostate cancer) | 14.2 | Medium-high expression |
| HEK293 (embryonic kidney) | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; associated with HHT2 |
| c.1567G>A (p.Gly523Arg) | Missense | <0.1% | Impaired kinase activity; HHT2 |
| c.2111A>G (p.Tyr704Cys) | Missense | <0.1% | Reduced ephrin-B2 binding; HHT2 |
| c.2450T>C (p.Ile817Thr) | Missense | <0.1% | Altered receptor dimerization; HHT2 |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish kinase activity or ligand binding, leading to HHT2.
Gain of Function (GOF)
Not well documented; some cancer-associated mutations may enhance signaling.
Dominant Negative (DN)
Some missense mutations may interfere with wild-type receptor function, contributing to HHT2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ephrin B reverse signaling
• Ephrin B forward signaling
• VEGF-VEGFR signaling pathway
• Angiogenesis
Protein Summary
EPHB4 is a 987-amino acid single-pass type I membrane protein with an N-terminal ephrin-binding domain, a cysteine-rich region, two fibronectin type III repeats, a transmembrane domain, and a cytoplasmic tyrosine kinase domain. It is activated by binding to ephrin-B2 ligands on adjacent cells, leading to autophosphorylation and downstream signaling that regulates cell repulsion, adhesion, and migration. EPHB4 is essential for vascular development and is implicated in tumor angiogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPHB4 Knockout HEK293 Cell Line | EDJ-KQ17792 | Human | 2050 | Details Get a Quote |
| EPHB4 Knockout A-549 Cell Line | EDJ-KQ19879 | Human | 2050 | Details Get a Quote |
| EPHB4 Knockout HCT 116 Cell Line | EDJ-KQ19880 | Human | 2050 | Details Get a Quote |
| EPHB4 Knockout HeLa Cell Line | EDJ-KQ19881 | Human | 2050 | Details Get a Quote |
