{"entity":{"id":"foxa1","kind":"target","name":"FOXA1","aka":["forkhead box A1","Hepatocyte nuclear factor 3-alpha","HNF3A"],"tldr":"FOXA1 (Hepatocyte nuclear factor 3-alpha) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Prostate cancer, Breast cancer, Neuroendocrine tumours and 1 more.","summary":"Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3'.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Aromatase Inhibitor. Open Targets scores its association with cancer at 0.79 (direct and indirect evidence; datatypes affected pathway 0.57, literature 1.00, genetic association 0.26, somatic mutation 0.97, animal model 0.30). IntOGen calls it a driver in 15 cohorts (11 activating, 4 loss-of-function), covering Invasive Breast Carcinoma, Prostate Adenocarcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:5021","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5021"},{"label":"UniProt P55317","url":"https://www.uniprot.org/uniprotkb/P55317/entry"},{"label":"NCBI Gene 3169","url":"https://www.ncbi.nlm.nih.gov/gene/3169"},{"label":"Ensembl ENSG00000129514","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000129514"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["prostate","breast-cancer","neuroendocrine","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["er-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-grasso-mutational-landscape-lethal-crpc-nature-2012","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015"],"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: CIViC lists 1 therapies; IntOGen calls it an activating (Act) driver in 11 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 4 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" 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":"FOXA1","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:5021","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5021","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P55317","url":"https://www.uniprot.org/uniprotkb/P55317/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene FOXA1","url":"https://civicdb.org/features/2662","note":"1 evidence items, 0 assertions, 1 variants; diseases: Oestrogen Receptor-positive Breast Cancer (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000129514","url":"https://platform.opentargets.org/target/ENSG00000129514/associations","note":"association with cancer (MONDO_0004992) 0.79; per-cancer scores at or above 0.5: prostate cancer 0.73, neuroendocrine neoplasm 0.51, breast cancer 0.72 (GraphQL API, CC0)"},{"label":"IntOGen FOXA1","url":"https://www.intogen.org/search?gene=FOXA1","note":"driver in 15 cohorts (Act 11, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"few-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 FOXA1: RNA tissue enhanced (prostate 70 nTPM); high antibody staining in 1 normal tissue; highest cancer staining breast cancer (10 of 11 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Prostate cancer, Breast cancer (all types), Neuroendocrine tumours); Open Targets associates it with 2 specific cancer types at or above 0.5 (prostate adenocarcinoma, breast adenocarcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P55317","url":"https://www.uniprot.org/uniprotkb/P55317/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene FOXA1","url":"https://civicdb.org/features/2662","note":"1 evidence items, 0 assertions, 1 variants; diseases: Oestrogen Receptor-positive Breast Cancer (GraphQL API, CC0)"},{"label":"IntOGen FOXA1","url":"https://www.intogen.org/search?gene=FOXA1","note":"driver in 15 cohorts (Act 11, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas FOXA1 tissue","url":"https://www.proteinatlas.org/ENSG00000129514-FOXA1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000129514 associations","url":"https://platform.opentargets.org/target/ENSG00000129514/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:5021","ensembl":"ENSG00000129514","uniprot":"P55317","entrez":"3169","firstDescribed":1996,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Bingle C.D. et al, Biochim. Biophys. Acta, 1996, \"Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8652662/","biology":"Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3'. Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Its differential recruitment to chromatin is dependent on distribution of histone H3 methylated at 'Lys-5' (H3K4me2) in oestrogen-regulated genes. Involved in the development of multiple endoderm-derived organ systems such as liver, pancreas, lung and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles. Location: Nucleus (UniProt). Locus 14q21.1 (HGNC).","whereFound":["Prostate cancer: Open Targets association 0.73 with prostate cancer (MONDO_0008315); IntOGen driver in 11 cohorts (PRAD)","Breast cancer: Open Targets association 0.72 with breast cancer (MONDO_0007254); IntOGen driver in 4 cohorts (BRCA)","Neuroendocrine tumours: Open Targets association 0.51 with neuroendocrine neoplasm (MONDO_0019496)","HR-positive / HER2-negative breast cancer: CIViC evidence names this disease","Prostate cancer: mutation clustered in the forkhead domain, plus amplification 2-16% depending on disease state"],"targetClass":"transcription","prevalence":[{"cancerId":"prostate","pct":"2-16","measure":"Mutation clustered in the forkhead domain, plus amplification","source":"https://www.cbioportal.org/study/summary?id=prostate_msk_2024","note":"cBioPortal mutation: 351 of 2,260, 15.5%, in prostate_msk_2024; 273 of 2,069, 13.2%, in prad_msk_stopsack_2021; 179 of 1,465, 12.2%, in prad_cdk12_mskcc_2020; 58 of 504, 11.5%, in prad_mskcc_2017; 50 of 424, 11.8%, in prad_mcspc_mskcc_2020; 69 of 1,013, 6.8%, in prad_p1000; 41 of 444, 9.2%, in prad_su2c_2019; 28 of 494, 5.7%, in prad_tcga_pan_can_atlas_2018; 11 of 477, 2.3%, in prad_cpcg_2017. Amplification adds 54 of 2,260 (2.4%) in prostate_msk_2024 and 21 of 149 (14.1%) in prad_fhcrc. It was first described as recurrent in 5 of 147 prostate cancers, 3.4%, across untreated and castration-resistant disease, where the mutant protein repressed androgen signalling and increased tumour growth (Grasso 2012)."}]},"route":"/targets/foxa1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"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":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"pathway":[{"id":"er-signaling","kind":"pathway","name":"Oestrogen receptor signalling","route":"/pathways/er-signaling/"}],"paper":[{"id":"paper-stopsack-prostate-genomes-by-race-ccr-2022","kind":"paper","name":"Differences in prostate cancer genomes by self-reported race","route":"/key-papers/paper-stopsack-prostate-genomes-by-race-ccr-2022/"},{"id":"paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012","kind":"paper","name":"Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer","route":"/key-papers/paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"},{"id":"paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018","kind":"paper","name":"The long tail of oncogenic drivers in prostate cancer","route":"/key-papers/paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018/"},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","route":"/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/"}]}}