FOXO1
FOXO1 (Forkhead box protein O1) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Non-Hodgkin lymphoma, Ovarian cancer and 4 more.
Overview
Transcription factor that is the main target of insulin signalling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin.
CIViC holds 2 clinical evidence items and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.71 (direct and indirect evidence; datatypes genetic literature 0.30, affected pathway 0.26, literature 0.99, genetic association 0.38, somatic mutation 0.83). IntOGen calls it a driver in 6 cohorts (5 activating, 1 loss-of-function), covering Burkitt Lymphoma, Lung Squamous Cell Carcinoma, Malignant Lymphoma, Non-Hodgkin Lymphoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · FOXO1 (Forkhead box protein O1) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Non-Hodgkin lymphoma, Ovarian cancer and 4 more.
- 1 · What it is
FOXO1 (Forkhead box protein O1) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Non-Hodgkin lymphoma, Ovarian cancer and 4 more.
- 2 · What goes wrong in cancer
Transcription factor that is the main target of insulin signalling and regulates metabolic homeostasis in response to oxidative stress.
- 3 · How drugs use it
No product in this corpus aims at FOXO1 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:3819 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q12778 (protein name, function text, keywords and locations (REST API)); CIViC gene FOXO1 (2 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma, Burkitt Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000150907 (association with cancer (MONDO_0004992) 0.71; per-cancer scores at or above 0.5: ovarian cancer 0.50, sarcoma 0.65, non-Hodgkin lymphoma 0.58, rhabdomyosarcoma 0.62 (GraphQL API, CC0)); IntOGen FOXO1 (driver in 6 cohorts (Act 5, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcription factor that is the main target of insulin signalling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation. Location: Cytoplasm; Nucleus (UniProt). Locus 13q14.11 (HGNC).
- Sarcomas: Open Targets association 0.65 with sarcoma (MONDO_0005089)
- Non-Hodgkin lymphoma: Open Targets association 0.58 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 3 cohorts (MLYM, NHL)
- Ovarian cancer: Open Targets association 0.50 with ovarian cancer (MONDO_0008170)
- Rhabdomyosarcoma: Open Targets association 0.62 with rhabdomyosarcoma (MONDO_0005212)
- Diffuse large B-cell lymphoma: CIViC evidence names this disease
- Burkitt lymphoma: CIViC evidence names this disease; IntOGen driver in 2 cohorts (BL)
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: IntOGen calls it an activating (Act) driver in 5 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 2 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. 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:"FOXO1" OR ABSTRACT:"FOXO1" OR TITLE:"forkhead box O1" OR ABSTRACT:"forkhead box O1" OR TITLE:"Forkhead box protein O1" OR ABSTRACT:"Forkhead box protein O1" OR TITLE:"FKH1" OR ABSTRACT:"FKH1" OR TITLE:"FOXO1A" OR ABSTRACT:"FOXO1A") 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 FOXO1, not a curated reading list.
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