{"entity":{"id":"epha3","kind":"target","name":"EPHA3","aka":["EPH receptor A3","Ephrin type-A receptor 3","HEK4","ETK1","TYRO4"],"tldr":"EPHA3 (Ephrin type-A receptor 3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver and a tumour suppressor, and an approved or late-stage drug is recorded against it. Tied to Neuroendocrine tumours, Thyroid cancer, Breast cancer and 5 more.","summary":"Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signalling into neighboring cells. The signalling pathway downstream of the receptor is referred to as forward signalling while the signalling pathway downstream of the ephrin ligand is referred to as reverse signalling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5.\n\nOpen Targets scores its association with cancer at 0.69 (direct and indirect evidence; datatypes genetic literature 0.30, clinical 0.93, affected pathway 0.61, literature 0.96, genetic association 0.26, somatic mutation 0.47, animal model 0.39). IntOGen calls it a driver in 5 cohorts (3 activating, 2 loss-of-function), covering Invasive Breast Carcinoma, Oesophageal Adenocarcinoma, Melanoma, Prostate Adenocarcinoma, Stomach Adenocarcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:3387","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3387"},{"label":"UniProt P29320","url":"https://www.uniprot.org/uniprotkb/P29320/entry"},{"label":"NCBI Gene 2042","url":"https://www.ncbi.nlm.nih.gov/gene/2042"},{"label":"Ensembl ENSG00000044524","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000044524"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["neuroendocrine","thyroid","breast-cancer","esophageal","prostate","gastric","oesophageal-adenocarcinoma","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.93; IntOGen calls it an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"EPHA3","role":["drug-target","oncogene-driver","tumour-suppressor"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:3387","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3387","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P29320","url":"https://www.uniprot.org/uniprotkb/P29320/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000044524","url":"https://platform.opentargets.org/target/ENSG00000044524/associations","note":"association with cancer (MONDO_0004992) 0.69; per-cancer scores at or above 0.5: thyroid cancer 0.62, neuroendocrine neoplasm 0.62 (GraphQL API, CC0)"},{"label":"IntOGen EPHA3","url":"https://www.intogen.org/search?gene=EPHA3","note":"driver in 5 cohorts (Act 3, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA EPHA3: RNA tissue enhanced (prostate 30 nTPM); no normal tissue stained high. Distribution: 7 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Neuroendocrine tumours, Thyroid cancer, Breast cancer (all types), Oesophageal cancer, Prostate cancer, Gastric & gastro-oesophageal junction cancer, Skin cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (medullary thyroid gland carcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P29320","url":"https://www.uniprot.org/uniprotkb/P29320/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"IntOGen EPHA3","url":"https://www.intogen.org/search?gene=EPHA3","note":"driver in 5 cohorts (Act 3, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas EPHA3 tissue","url":"https://www.proteinatlas.org/ENSG00000044524-EPHA3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000044524 associations","url":"https://platform.opentargets.org/target/ENSG00000044524/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:3387","ensembl":"ENSG00000044524","uniprot":"P29320","entrez":"2042","firstDescribed":1992,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Wicks I.P. et al, Proc. Natl. Acad. Sci. U.S.A, 1992, \"Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1311845/","biology":"Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signalling into neighboring cells. The signalling pathway downstream of the receptor is referred to as forward signalling while the signalling pathway downstream of the ephrin ligand is referred to as reverse signalling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organisation and cell migration. Also activated by EFNA1, inhibiting epithelial-to-mesenchymal transition of cardiac cells and playing a role in heart development. Involved in the retinotectal mapping of neurons. Location: Cell membrane; Secreted (UniProt). Locus 3p11.1 (HGNC).","whereFound":["Neuroendocrine tumours: Open Targets association 0.62 with neuroendocrine neoplasm (MONDO_0019496)","Thyroid cancer: Open Targets association 0.62 with thyroid cancer (MONDO_0002108)","Breast cancer: IntOGen driver in 1 cohort (BRCA)","Oesophageal cancer: IntOGen driver in 1 cohort (ESCA)","Prostate cancer: IntOGen driver in 1 cohort (PRAD)","Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (STAD)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/epha3/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","route":"/cancers/oesophageal-adenocarcinoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}]}}