FOXO1 Gene

HGNC Family	Forkhead boxes (FOX)
Name	forkhead box O1
Description	This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FOXO1 is a multifaceted transcription factor that integrates nutrient, hormonal, and stress signals to orchestrate a broad range of physiological processes. In metabolic tissues, FOXO1 activity is modulated by energy sensors: for instance, its deacetylation by SIRT1 downstream of AMPK activation enhances the transcription of genes involved in oxidative metabolism, thereby adapting cellular energy homeostasis to low‐energy states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In skeletal muscle, FOXO1 is tightly regulated by the IGF-1/PI3K/Akt pathway; Akt-mediated phosphorylation normally restrains FOXO1 activity, and mutations that prevent this phosphorylation lead to the upregulation of atrophy-associated ubiquitin ligases, tipping the balance toward muscle catabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In the liver, FOXO1 cooperates with the coactivator PGC-1α to induce gluconeogenic gene expression—a process that is suppressed by insulin through Akt-dependent phosphorylation, thus serving as a key node in the regulation of hepatic glucose production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, additional layers of regulation arise from mTORC2 signaling, which influences FOXO1 phosphorylation and selectively modulates its downstream targets."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the immune system, FOXO1 activity is instrumental in determining cell fate; for example, in TH17 cells, SGK1 deactivates FOXO1 to lift its repression of the IL-23 receptor, thereby stabilizing a pathogenic phenotype"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while in T lymphocytes, IL-2 signaling evokes PI3K-dependent phosphorylation of FOXO1 to promote cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In adipocytes, FOXO1 helps mediate the transcriptional program governing differentiation and is subject to insulin-mediated inactivation, highlighting its role in adipose tissue development and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Its critical role is further underscored in vascular biology, where genetic ablation of FOXO1 disrupts vascular formation and leads to embryonic lethality, emphasizing its necessity for proper angiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, aberrant FOXO1 regulation contributes to metabolic diseases; for instance, improper insulin signaling that fails to inhibit FOXO1 activity in liver, adipose tissue, and pancreatic β-cells can exacerbate insulin resistance and hyperglycemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Beyond metabolism, FOXO1 is implicated in longevity and stress resistance as its transcriptional output is modulated by reversible acetylation through SIRT1 activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and in cancer, its tumor-suppressive function can be compromised by microRNAs that downregulate FOXO1 expression, thereby favoring oncogenic transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In addition, under nutrient or oxidative stress conditions, FOXO1 contributes to the regulation of autophagic flux by interacting with components of the autophagy machinery, a mechanism important for cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, in endothelial cells, FOXO1 is a key mediator linking cell–cell junction dynamics to vascular barrier integrity; Akt-dependent phosphorylation relieves FOXO1-mediated repression of tight junction proteins such as claudin-5, thereby coupling adherens and tight junction function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carles Cantó, Zachary Gerhart-Hines, Jerome N Feige, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07813"}], "href": "https://doi.org/10.1038/nature07813"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19262508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19262508"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Trevor N Stitt, Doreen Drujan, Brian A Clarke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(04)00211-4"}], "href": "https://doi.org/10.1016/s1097-2765(04"}, {"type": "t", "text": "00211-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15125842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15125842"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Pere Puigserver, James Rhee, Jerry Donovan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01667"}], "href": "https://doi.org/10.1038/nature01667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12754525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12754525"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Estela Jacinto, Valeria Facchinetti, Dou Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2006.08.033"}], "href": "https://doi.org/10.1016/j.cell.2006.08.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16962653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16962653"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chuan Wu, Nir Yosef, Theresa Thalhamer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11984"}], "href": "https://doi.org/10.1038/nature11984"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23467085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23467085"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marie Stahl, Pascale F Dijkers, Geert J P L Kops, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.168.10.5024"}], "href": "https://doi.org/10.4049/jimmunol.168.10.5024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11994454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11994454"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jun Nakae, Tadahiro Kitamura, Yukari Kitamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The forkhead transcription factor Foxo1 regulates adipocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1534-5807(02)00401-x"}], "href": "https://doi.org/10.1016/s1534-5807(02"}, {"type": "t", "text": "00401-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12530968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12530968"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Taisuke Hosaka, William H Biggs, David Tieu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0400093101"}], "href": "https://doi.org/10.1073/pnas.0400093101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14978268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14978268"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jun Nakae, William H Biggs, Tadahiro Kitamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng890"}], "href": "https://doi.org/10.1038/ng890"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12219087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12219087"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hiroaki Daitoku, Mitsutoki Hatta, Hitomi Matsuzaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0400593101"}], "href": "https://doi.org/10.1073/pnas.0400593101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15220471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15220471"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Irene K Guttilla, Bruce A White "}, {"type": "b", "children": [{"type": "t", "text": "Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.031427"}], "href": "https://doi.org/10.1074/jbc.M109.031427"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19574223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19574223"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ying Zhao, Jing Yang, Wenjuan Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2069"}], "href": "https://doi.org/10.1038/ncb2069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20543840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20543840"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Andrea Taddei, Costanza Giampietro, Annarita Conti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1752"}], "href": "https://doi.org/10.1038/ncb1752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18604199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18604199"}]}]}]}
Synonyms	FOXO1A, FKH1, FKHR
Proteins	FOXO1_HUMAN
NCBI Gene ID	2308
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FOXO1 has 16,863 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 140 datasets.

Click the + buttons to view associations for FOXO1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FOXO1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FOXO1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of FOXO1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of FOXO1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of FOXO1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of FOXO1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FOXO1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving FOXO1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of FOXO1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FOXO1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FOXO1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FOXO1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of FOXO1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with FOXO1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with FOXO1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with FOXO1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FOXO1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FOXO1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of FOXO1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing FOXO1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of FOXO1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FOXO1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FOXO1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing FOXO1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with FOXO1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with FOXO1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing FOXO1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of FOXO1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FOXO1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FOXO1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FOXO1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of FOXO1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by FOXO1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving FOXO1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving FOXO1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with FOXO1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with FOXO1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with FOXO1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with FOXO1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with FOXO1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FOXO1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.