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25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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EPHA2
EPH receptor A2
Chromosome 1 Β· 1p36.13
NCBI Gene: 1969Ensembl: ENSG00000142627.14HGNC: HGNC:3386UniProt: P29317
453PubMed Papers
21Diseases
3Drugs
17Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinaseReceptor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
molecular function activator activityephrin receptor signaling pathwaypositive regulation of bicellular tight junction assemblycell motilityTotal congenital cataractPosterior polar cataractearly-onset non-syndromic cataractchronic myelogenous leukemia
✦AI Summary

EPHA2 (EPH receptor A2) is a receptor tyrosine kinase functioning as a multifaceted signaling hub in cancer biology and viral pathogenesis. Canonically, EPHA2 regulates cell migration, focal adhesion assembly, and growth factor signaling through ephrin-dependent mechanisms 1. Beyond classical ephrin signaling, EPHA2 acts as a viral entry receptor for both Epstein-Barr virus and cytomegalovirus in epithelial cells, interacting with viral glycoproteins gH/gL and gB to facilitate internalization 2. In glioblastoma, EPHA2 mediates platelet-derived growth factor A (PDGFA) activity independently of PDGFRA, contributing to malignant progression and therapeutic resistance 3. EPHA2 oncogenic activity extends across multiple cancer types through diverse mechanisms: m6A-methylated EPHA2 promotes vasculogenic mimicry in colorectal cancer via PI3K/AKT and ERK1/2 signaling 1; EPHA2 interaction with claudin-1 enhances cancer stemness and chemoresistance through AKT-CD44 axis activation 4; and hypoxia-induced TGFBI stabilizes EPHA2 protein to maintain glioma stem cell properties 5. In hepatic fibrosis, EPHA2/FAK/Src signaling regulates stellate cell glycolysis and activation 6. EPHA2 overexpression associates with poor prognosis across malignancies 7. Therapeutic strategies include dual EPHA2/PDGFRA inhibition, bicyclic peptide-based radiotheranostics 8, and emerging proteolysis-targeting chimera approaches 7.

Sources cited
1
Canonically, EPHA2 regulates cell migration, focal adhesion assembly, and growth factor signaling through ephrin-dependent mechanisms .
PMID: 35595748
2
Beyond classical ephrin signaling, EPHA2 acts as a viral entry receptor for both Epstein-Barr virus and cytomegalovirus in epithelial cells, interacting with viral glycoproteins gH/gL and gB to facilitate internalization .
PMID: 29292383
3
In glioblastoma, EPHA2 mediates platelet-derived growth factor A (PDGFA) activity independently of PDGFRA, contributing to malignant progression and therapeutic resistance .
PMID: 35105853
4
EPHA2 oncogenic activity extends across multiple cancer types through diverse mechanisms: m6A-methylated EPHA2 promotes vasculogenic mimicry in colorectal cancer via PI3K/AKT and ERK1/2 signaling ; EPHA2 interaction with claudin-1 enhances cancer stemness and chemoresistance through AKT-CD44 axis activation ; and hypoxia-induced TGFBI stabilizes EPHA2 protein to maintain glioma stem cell properties .
PMID: 37924938
5
EPHA2 oncogenic activity extends across multiple cancer types through diverse mechanisms: m6A-methylated EPHA2 promotes vasculogenic mimicry in colorectal cancer via PI3K/AKT and ERK1/2 signaling ; EPHA2 interaction with claudin-1 enhances cancer stemness and chemoresistance through AKT-CD44 axis activation ; and hypoxia-induced TGFBI stabilizes EPHA2 protein to maintain glioma stem cell properties .
PMID: 39346536
6
In hepatic fibrosis, EPHA2/FAK/Src signaling regulates stellate cell glycolysis and activation .
PMID: 39321687
7
EPHA2 overexpression associates with poor prognosis across malignancies .
PMID: 39596256
8
Therapeutic strategies include dual EPHA2/PDGFRA inhibition, bicyclic peptide-based radiotheranostics , and emerging proteolysis-targeting chimera approaches .
PMID: 39239524
Disease Associationsβ“˜21
Total congenital cataractOpen Targets
0.77Strong
Posterior polar cataractOpen Targets
0.77Strong
early-onset non-syndromic cataractOpen Targets
0.68Moderate
chronic myelogenous leukemiaOpen Targets
0.59Moderate
colorectal cancerOpen Targets
0.56Moderate
neurodegenerative diseaseOpen Targets
0.56Moderate
neoplasmOpen Targets
0.55Moderate
metastatic colorectal cancerOpen Targets
0.55Moderate
acute lymphoblastic leukemiaOpen Targets
0.53Moderate
medullary thyroid gland carcinomaOpen Targets
0.52Moderate
colorectal neoplasmOpen Targets
0.49Moderate
cataractOpen Targets
0.47Moderate
cholangiocarcinomaOpen Targets
0.44Moderate
genetic disorderOpen Targets
0.42Moderate
non-small cell lung carcinomaOpen Targets
0.41Moderate
hepatocellular carcinomaOpen Targets
0.41Moderate
early-onset nuclear cataractOpen Targets
0.39Weak
lymphoid leukemiaOpen Targets
0.39Weak
thyroid neoplasmOpen Targets
0.39Weak
Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveOpen Targets
0.39Weak
Cataract 6, multiple typesUniProt
Pathogenic Variants17
NM_004431.5(EPHA2):c.2826-9G>APathogenic
not provided|Cataract 6 multiple types|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025
NM_004431.5(EPHA2):c.2903_2904del (p.Gln968fs)Pathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2024β†’ Residue 968
NM_004431.5(EPHA2):c.2475+1G>ALikely pathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2023
NM_004431.5(EPHA2):c.2928_2929del (p.Ile976fs)Likely pathogenic
EPHA2-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 976
NM_004431.5(EPHA2):c.2426_2427dup (p.Val810fs)Pathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2022β†’ Residue 810
NM_004431.5(EPHA2):c.988dup (p.Ser330fs)Pathogenic
Cataract 6 multiple types|EPHA2-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 330
NM_004431.5(EPHA2):c.2353G>A (p.Ala785Thr)Likely pathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2022β†’ Residue 785
NM_004431.5(EPHA2):c.2825+2delPathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2022
NM_004431.5(EPHA2):c.2815_2825+9delPathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2021
NM_004431.5(EPHA2):c.41G>A (p.Trp14Ter)Pathogenic
Congenital aniridia;Cataract;Bilateral microphthalmos
β˜…β˜†β˜†β˜†2021β†’ Residue 14
NM_004431.5(EPHA2):c.2891del (p.Gly964fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 964
NM_004431.5(EPHA2):c.2915_2916del (p.Val972fs)Pathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2019β†’ Residue 972
NM_004431.5(EPHA2):c.759G>A (p.Trp253Ter)Pathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2018β†’ Residue 253
NM_004431.5(EPHA2):c.1582+1G>ALikely pathogenic
Cataract 6 multiple types
β˜…β˜†β˜†β˜†2018
NM_004431.5(EPHA2):c.2007G>T (p.Gln669His)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†β†’ Residue 669
NM_004431.5(EPHA2):c.2819C>T (p.Thr940Ile)Pathogenic
Cataract 6 multiple types
β˜†β˜†β˜†β˜†2009β†’ Residue 940
NM_004431.5(EPHA2):c.2842G>T (p.Gly948Trp)Pathogenic
Cataract 6 multiple types
β˜†β˜†β˜†β˜†2008β†’ Residue 948
View on ClinVar β†—
Drug Targets3
DASATINIB ANHYDROUSApproved
Bcr/Abl fusion protein inhibitor
acute lymphoblastic leukemia
REGORAFENIBApproved
Discoidin domain-containing receptor 2 inhibitor
colorectal cancer
VANDETANIBApproved
Ephrin receptor inhibitor
Related Genes
EFNA2Protein interaction100%CRKLProtein interaction100%PIK3R1Protein interaction100%EPHA4Protein interaction100%INPPL1Protein interaction97%FGF2Protein interaction96%
Tissue Expression6 tissues
Heart
100%
Liver
98%
Lung
81%
Ovary
34%
Brain
12%
Bone Marrow
7%
Gene Interaction Network
Click a node to explore
EPHA2EFNA2CRKLPIK3R1EPHA4INPPL1FGF2
PROTEIN STRUCTURE
Preparing viewer…
PDB6Q7D Β· 0.98 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.65LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.52 [0.42–0.65]
RankingsWhere EPHA2 stands among ~20K protein-coding genes
  • #605of 20,598
    Most Researched453 Β· top 5%
  • #449of 1,025
    FDA-Approved Drug Targets3
  • #2,309of 5,498
    Most Pathogenic Variants17
  • #4,738of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedEPHA2
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
EPHA2 mediates PDGFA activity and functions together with PDGFRA as prognostic marker and therapeutic target in glioblastoma.
PMID: 35105853
Signal Transduct Target Ther Β· 2022
1.00
2
m6A methylated EphA2 and VEGFA through IGF2BP2/3 regulation promotes vasculogenic mimicry in colorectal cancer via PI3K/AKT and ERK1/2 signaling.
PMID: 35595748
Cell Death Dis Β· 2022
0.90
3
Claudin-1 interacts with EPHA2 to promote cancer stemness and chemoresistance in colorectal cancer.
PMID: 37924938
Cancer Lett Β· 2023
0.80
4
Ephrin-A3/EphA2 axis regulates cellular metabolic plasticity to enhance cancer stemness in hypoxic hepatocellular carcinoma.
PMID: 35227773
J Hepatol Β· 2022
0.76
5
PTEN Loss Promotes PI3KΞ² Phosphorylation and EPHA2/SRC/p-PI3KΞ²Y962 Complex Assembly to Drive Tumorigenesis.
PMID: 41237375
Cancer Discov Β· 2026
0.72