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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.
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'.
CIViC 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.
In plain words · 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.
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.
Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues.
No product in this corpus aims at FOXA1 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
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.)
Sources: UniProt P55317; CIViC gene FOXA1; IntOGen FOXA1; Human Protein Atlas FOXA1 tissue; Open Targets ENSG00000129514 associations
First described 1996. 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". Source.
Sources: HGNC HGNC:5021 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P55317 (protein name, function text, keywords and locations (REST API)); CIViC gene FOXA1 (1 evidence items, 0 assertions, 1 variants; diseases: Oestrogen Receptor-positive Breast Cancer (GraphQL API, CC0)); Open Targets ENSG00000129514 (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)); IntOGen FOXA1 (driver in 15 cohorts (Act 11, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
RNA: tissue enhanced (prostate 70 nTPM), detected in many normal tissues.
Medium: Bronchus, Nasopharynx, Stomach, Tonsil, Urinary bladder.
RNA group enriched: Breast Invasive Carcinoma 140 pTPM, Prostate Adenocarcinoma 201 pTPM.
Medium only: carcinoid, endometrial cancer, pancreatic cancer, stomach cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 2-16% | Mutation clustered in the forkhead domain, plus amplification | 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). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It separates two explanations that are usually run together. Some of the difference in prostate cancer outcomes by race is in the tumour genome and persists when access to the same centre is held constant, and some of it tracks with income rather than with ancestry, so equalising access alone would not eliminate the gap.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
The reference classification of prostate cancer as it presents, and the source of the two numbers that drive most molecular treatment decisions in the disease: a quarter with a PI3K or MAPK lesion, which is the rationale for capivasertib in PTEN-deficient disease, and a fifth with DNA repair inactivation, which is the rationale for PARP inhibitors.
It established the fusion-negative side of the prostate cancer taxonomy and made SPOP the disease's signature point mutation, in a ubiquitin ligase adaptor rather than in a kinase, which is part of why prostate cancer has so few druggable drivers.
The explanation for why prostate cancer has so few targeted drugs outside the hormone axis and the DNA-repair genes: it is a quiet genome with structural rather than point-mutational damage, and the recurrent changes sit in the machinery that reads DNA rather than in kinases.
Query for this target: (TITLE:"FOXA1" OR ABSTRACT:"FOXA1" OR TITLE:"forkhead box A1" OR ABSTRACT:"forkhead box A1" OR TITLE:"Hepatocyte nuclear factor 3-alpha" OR ABSTRACT:"Hepatocyte nuclear factor 3-alpha" OR TITLE:"HNF3A" OR ABSTRACT:"HNF3A") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FOXA1, not a curated reading list.
Shares Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, The long tail of oncogenic drivers in prostate cancer, TCGA: the molecular taxonomy of primary prostate cancer, CIViC.
Shares Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, The long tail of oncogenic drivers in prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, TCGA: the molecular taxonomy of primary prostate cancer.
Shares The long tail of oncogenic drivers in prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, CIViC, IntOGen.
Shares The long tail of oncogenic drivers in prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, Neuroendocrine tumours, CIViC.
Shares TCGA: the molecular taxonomy of primary prostate cancer, CIViC, IntOGen, Breast cancer (all types).
Shares Differences in prostate cancer genomes by self-reported race, IntOGen, Breast cancer (all types), Open Targets Platform.
Shares Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, The long tail of oncogenic drivers in prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, TCGA: the molecular taxonomy of primary prostate cancer.
Shares The mutational landscape of lethal castration-resistant prostate cancer, TCGA: the molecular taxonomy of primary prostate cancer, IntOGen, Open Targets Platform.