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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EPHA1
EPH receptor A1
Chromosome 7 · 7q34-q35
NCBI Gene: 2041Ensembl: ENSG00000146904.10HGNC: HGNC:3385UniProt: P21709
84PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
KinaseReceptor
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
substrate adhesion-dependent cell spreadingephrin receptor activitypositive regulation of cell migrationnegative regulation of cell migrationAlzheimer diseasemedullary thyroid gland carcinomaneoplasmnon-small cell lung carcinoma
✦AI Summary

EPHA1 is a receptor tyrosine kinase that binds ephrin-A ligands (particularly EFNA1) on adjacent cells to initiate contact-dependent bidirectional signaling. Upon activation, EPHA1 promotes cell attachment to the extracellular matrix while inhibiting cell spreading and motility through ILK, RHOA, and RAC regulation 1. The receptor plays established roles in angiogenesis and cell proliferation 2. EPHA1 has emerged as a significant disease-relevant gene identified through genome-wide association studies. It is a confirmed Alzheimer's disease (AD) risk gene 3, with recent evidence identifying EPHA1 as one of seven proteins with structural alterations due to missense mutations in AD pathogenesis 4. Experimental studies in Drosophila demonstrate that EphA1 dysfunction affects sleep architecture, circadian rhythm, neuronal excitability, and memory—behavioral phenotypes relevant to AD 1. EPHA1 is also implicated in neuroinflammatory mechanisms linked to AD progression 5. Beyond neurodegeneration, EPHA1 represents a key oncogenic driver across multiple cancers including hepatocellular carcinoma, nasopharyngeal carcinoma, ovarian cancer, gastric cancer, and breast cancer, where it contributes to tumor progression and angiogenesis 678. EPHA1 expression changes serve as biomarkers for cancer diagnosis and prognosis, with potential as a therapeutic target through structural modification or receptor inhibition 6.

Sources cited
1
EPHA1 identified as a genetic risk factor for late-onset Alzheimer's disease
PMID: 24951455
2
EphA1 and ephrin-A1 functions related to tumor angiogenesis and lung metastasis
PMID: 30657619
3
EphA1 mis-expression affects sleep architecture, circadian rhythm, and neuronal excitability in Drosophila model
PMID: 35569721
4
EphA1 identified as oncoprotein in multiple tumor types and prognostic marker for cancer
PMID: 35996244
5
Eph receptor-ephrin signaling mechanisms in cancer progression, drug resistance, and tumor microenvironment interactions
PMID: 37996538
6
EPHA1 identified as protein with structural alterations due to missense mutations in Alzheimer's disease
PMID: 39637861
7
Ephrin ligands and receptors including EphA1 contribute to angiogenesis; Ephrin receptor blockers used in cancer treatment
PMID: 41077163
8
EPHA1 among genetic variants potentially linked to neuroinflammation in Alzheimer's disease
PMID: 32296418
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.58Moderate
medullary thyroid gland carcinomaOpen Targets
0.52Moderate
neoplasmOpen Targets
0.42Moderate
non-small cell lung carcinomaOpen Targets
0.39Weak
thyroid neoplasmOpen Targets
0.39Weak
thyroid carcinomaOpen Targets
0.37Weak
lung cancerOpen Targets
0.35Weak
Parkinson diseaseOpen Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.34Weak
lysosomal storage diseaseOpen Targets
0.34Weak
multiple sclerosisOpen Targets
0.34Weak
thyroid cancerOpen Targets
0.34Weak
late-onset Alzheimers diseaseOpen Targets
0.23Weak
pathological myopiaOpen Targets
0.21Weak
breast cancerOpen Targets
0.12Weak
bladder exstrophyOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
prostate cancerOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
response to xenobiotic stimulusOpen Targets
0.10Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
VANDETANIBApproved
Ephrin receptor inhibitor
Related Genes
ADAM10Protein interaction100%EFNA2Protein interaction100%EPHB1Protein interaction100%EFNA3Protein interaction100%EFNA4Protein interaction100%EFNB1Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Lung
29%
Bone Marrow
14%
Ovary
6%
Heart
3%
Brain
1%
Gene Interaction Network
Click a node to explore
EPHA1ADAM10EFNA2EPHB1EFNA3EFNA4EFNB1
PROTEIN STRUCTURE
Preparing viewer…
PDB3HIL · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.99LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.83 [0.70–0.99]
RankingsWhere EPHA1 stands among ~20K protein-coding genes
  • #5,664of 20,598
    Most Researched84
  • #961of 1,025
    FDA-Approved Drug Targets1
  • #9,483of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedEPHA1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Alzheimer's disease risk genes and mechanisms of disease pathogenesis.
PMID: 24951455
Biol Psychiatry · 2015
1.00
2
Eph receptors and ephrins in cancer progression.
PMID: 37996538
Nat Rev Cancer · 2024
0.90
3
Roles of EphA1/A2 and ephrin-A1 in cancer.
PMID: 30657619
Cancer Sci · 2019
0.80
4
Deciphering proteins in Alzheimer's disease: A new Mendelian randomization method integrated with AlphaFold3 for 3D structure prediction.
PMID: 39637861
Cell Genom · 2024
0.70
5
The Functions of EphA1 Receptor Tyrosine Kinase in Several Tumors.
PMID: 35996244
Curr Med Chem · 2023
0.60