EPHA4: Ephrin Type-A Receptor 4
A key regulator of axon guidance, synaptic plasticity, and cancer progression
Gene Information Card
| Symbol | EPHA4 |
|---|---|
| Full Name | EPH receptor A4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q36.1 |
| NCBI Gene ID | 2043 ncbi.nlm.nih.gov/gene/2043 |
| Ensembl ID | ENSG00000116106 |
| UniProt ID | P54764 |
| OMIM ID | 602188 |
| HGNC ID | 3388 |
| Aliases | HEK8, SEK, TYRO1 |
Description
EPHA4 (EPH receptor A4) encodes a member of the ephrin receptor subfamily of receptor tyrosine kinases. It binds ephrin-A ligands (e.g., EFNA1, EFNA3, EFNA4) and ephrin-B ligands (e.g., EFNB2, EFNB3) to regulate cell adhesion, migration, axon guidance, and synaptic plasticity. EPHA4 is involved in nervous system development, angiogenesis, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic lateral sclerosis (ALS) | EPHA4 downregulation or loss-of-function mutations reduce motor neuron vulnerability and slow disease progression | PMID: 22902753 |
| Colorectal cancer | EPHA4 overexpression promotes tumor cell migration and invasion via ephrin-A1 reverse signaling | PMID: 19151741 |
| Breast cancer | EPHA4 expression correlates with poor prognosis; promotes metastasis through RhoA/ROCK pathway | PMID: 23555253 |
| Prostate cancer | EPHA4 upregulation associated with castration-resistant progression and neuroendocrine differentiation | PMID: 25652387 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.5 | High |
| Spinal cord | 22.1 | High |
| Lung | 6.3 | Low |
| Colon | 4.8 | Low |
| Breast | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 35.2 | High expression; used in neuronal differentiation studies |
| MCF7 (breast cancer) | 12.4 | Moderate expression |
| HCT116 (colorectal cancer) | 8.9 | Low expression |
| A549 (lung cancer) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2815C>T (p.Arg939Cys) | Missense | 0.01% (gnomAD) | Reduced kinase activity; associated with ALS |
| c.1960G>A (p.Glu654Lys) | Missense | 0.005% (gnomAD) | Altered ligand binding; uncertain significance |
| c.1234_1235insA (p.Thr412Asnfs*2) | Frameshift | Rare | Loss-of-function; reported in ALS |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) reduce EPHA4 kinase activity and are associated with slower ALS progression.
Gain of Function (GOF)
Gain-of-function mutations (e.g., certain missense variants) may enhance EPHA4 signaling and promote cancer cell migration.
Dominant Negative (DN)
Dominant-negative effects have not been clearly documented for EPHA4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ephrin-A forward signaling (Reactome: R-HSA-3928662)
• Ephrin-B reverse signaling (Reactome: R-HSA-3928665)
• Axon guidance (KEGG: hsa04360)
• Signaling by receptor tyrosine kinases (Reactome: R-HSA-9006934)
Protein Summary
EPHA4 is a 986-amino acid receptor tyrosine kinase with an extracellular ephrin-binding domain, a single transmembrane helix, and an intracellular kinase domain. Upon ligand binding, it autophosphorylates and recruits downstream effectors such as Src, FAK, and Rho GTPases to regulate cytoskeletal dynamics, cell adhesion, and migration. EPHA4 is highly expressed in the nervous system and plays critical roles in axon guidance, synaptic plasticity, and neurodevelopment. Aberrant EPHA4 signaling contributes to cancer metastasis and neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPHA4 Knockout HEK293 Cell Line | EDJ-KQ3334 | Human | 2043 | Details Get a Quote |
| EPHA4 Knockout A-549 Cell Line | EDJ-KQ24969 | Human | 2043 | Details Get a Quote |
| EPHA4 Knockout HCT 116 Cell Line | EDJ-KQ24970 | Human | 2043 | Details Get a Quote |
| EPHA4 Knockout HeLa Cell Line | EDJ-KQ24971 | Human | 2043 | Details Get a Quote |
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