{"entity":{"id":"foxo3","kind":"target","name":"FOXO3","aka":["forkhead box O3","Forkhead box protein O3","AF6q21","FOXO2","FKHRL1","FOXO3A"],"tldr":"FOXO3 (Forkhead box protein O3) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Breast cancer, Skin cancer, Acute myeloid leukaemia and 1 more.","summary":"Transcriptional activator that recognises and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy. Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins. Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress.\n\nOpen Targets scores its association with cancer at 0.65 (direct and indirect evidence; datatypes literature 1.00, animal model 0.41, genetic association 0.05, somatic mutation 0.77). IntOGen calls it a driver in 2 cohorts (2 activating, 0 loss-of-function), covering Acute Myeloid Leukaemia, Medulloblastoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:3821","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3821"},{"label":"UniProt O43524","url":"https://www.uniprot.org/uniprotkb/O43524/entry"},{"label":"NCBI Gene 2309","url":"https://www.ncbi.nlm.nih.gov/gene/2309"},{"label":"Ensembl ENSG00000118689","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118689"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["breast-cancer","skin-cancer","aml","medulloblastoma"],"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: IntOGen calls it an activating (Act) driver in 2 cohorts; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier \"cohort-driver\" 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":"FOXO3","role":["oncogene-driver","fusion-partner"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:3821","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3821","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O43524","url":"https://www.uniprot.org/uniprotkb/O43524/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000118689","url":"https://platform.opentargets.org/target/ENSG00000118689/associations","note":"association with cancer (MONDO_0004992) 0.65; per-cancer scores at or above 0.5: skin cancer 0.52, breast cancer 0.54 (GraphQL API, CC0)"},{"label":"IntOGen FOXO3","url":"https://www.intogen.org/search?gene=FOXO3","note":"driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:3821","ensembl":"ENSG00000118689","uniprot":"O43524","entrez":"2309","biology":"Transcriptional activator that recognises and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy. Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins. Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation. In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Location: Cytoplasm, cytosol; Nucleus; Mitochondrion matrix; Mitochondrion outer membrane (UniProt). Locus 6q21 (HGNC).","whereFound":["Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254)","Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)","Acute myeloid leukaemia: IntOGen driver in 1 cohort (AML)","Medulloblastoma: IntOGen driver in 1 cohort (MBL)"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/foxo3/","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":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"medulloblastoma","kind":"cancer","name":"Medulloblastoma","route":"/cancers/medulloblastoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}