FOXA1
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues.
- 3 · How drugs use it
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.
External identifiers
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)
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).
- 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
Notes
top- 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.
Latest papers
topQuery 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.
Similar pages
not linked directly; found by shared links- PairingCDK4/6 inhibitor + endocrine therapy
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