FOXO1
Forkhead box protein O1
Also known as: FKH1, FKHR, FOXO1_HUMAN, FOXO1A
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q12778
- Gene
- FOXO1
- Ensembl
- ENSG00000150907
- Chromosome
- 13
- Canonical length
- 655 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Cytosol
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
655 residues, UniProt reviewed canonical sequence.
>Q12778|FOXO1
1 MAEAPQVVEI DPDFEPLPRP RSCTWPLPRP EFSQSNSATS SPAPSGSAAA NPDAAAGLPS
61 ASAAAVSADF MSNLSLLEES EDFPQAPGSV AAAVAAAAAA AATGGLCGDF QGPEAGCLHP
121 APPQPPPPGP LSQHPPVPPA AAGPLAGQPR KSSSSRRNAW GNLSYADLIT KAIESSAEKR
181 LTLSQIYEWM VKSVPYFKDK GDSNSSAGWK NSIRHNLSLH SKFIRVQNEG TGKSSWWMLN
241 PEGGKSGKSP RRRAASMDNN SKFAKSRSRA AKKKASLQSG QEGAGDSPGS QFSKWPASPG
301 SHSNDDFDNW STFRPRTSSN ASTISGRLSP IMTEQDDLGE GDVHSMVYPP SAAKMASTLP
361 SLSEISNPEN MENLLDNLNL LSSPTSLTVS TQSSPGTMMQ QTPCYSFAPP NTSLNSPSPN
421 YQKYTYGQSS MSPLPQMPIQ TLQDNKSSYG GMSQYNCAPG LLKELLTSDS PPHNDIMTPV
481 DPGVAQPNSR VLGQNVMMGP NSVMSTYGSQ ASHNKMMNPS SHTHPGHAQQ TSAVNGRPLP
541 HTVSTMPHTS GMNRLTQVKT PVQVPLPHPM QMSALGGYSS VSSCNGYGRM GLLHQEKLPS
601 DLDGMFIERL DCDMESIIRN DLMDGDTLDF NFDNVLPNQS FPHSVKTTTH SWVSGLocalizationUniProt · AlphaFold · HPA
Whether an antibody against FOXO1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.68
- Highest tissue expression
- 84 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 84 nTPM
- ovary: 48 nTPM
- adipose tissue: 41 nTPM
- liver: 36 nTPM
- endometrium: 35 nTPM
- breast: 27 nTPM
Single-cell type
- adipocytes: 983 nCPM
- somatotrophs: 976 nCPM
- thymic myoid cells: 922 nCPM
- renal collecting duct intercalated cells: 873 nCPM
- endometrial stromal cells: 609 nCPM
- decidual stromal cells: 606 nCPM
Immune cell
- naive B-cell: 5.9 nTPM
- naive CD4 T-cell: 5.5 nTPM
- T-reg: 5.1 nTPM
- naive CD8 T-cell: 4.3 nTPM
- memory B-cell: 3.7 nTPM
- memory CD4 T-cell: 3.6 nTPM
Brain region
- choroid plexus: 35 nTPM
- basal ganglia: 33 nTPM
- medulla oblongata: 30 nTPM
- white matter: 28 nTPM
- midbrain: 26 nTPM
- hypothalamus: 25 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about FOXO1.
Disease | AllUniProt
Conditions FOXO1 is implicated in, by any mechanism.
- Rhabdomyosarcoma 2 (RMS2) MIM:268220
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 95 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.17
- gnomAD pLI
- 1
- gnomAD missense Z
- 1.71
- DepMap mean gene effect
- -0.15
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process
- autophagy
- blood vessel development
- canonical Wnt signaling pathway
- cellular response to cold
- cellular response to hyperoxia
- cellular response to insulin stimulus
- cellular response to nitric oxide
- cellular response to oxidative stress
- cellular response to starvation
- DNA damage response
- energy homeostasis
- fat cell differentiation
- gene expression
- insulin receptor signaling pathway
- intracellular glucose homeostasis
- negative regulation of apoptotic process
- negative regulation of canonical Wnt signaling pathway
- negative regulation of cardiac muscle hypertrophy in response to stress
- negative regulation of DNA-templated transcription
- negative regulation of fat cell differentiation
- negative regulation of insulin secretion
- negative regulation of stress-activated MAPK cascade
- neuronal stem cell population maintenance
- positive regulation of apoptotic process
- positive regulation of autophagy
- positive regulation of DNA-templated transcription
- positive regulation of gluconeogenesis
- positive regulation of protein catabolic process
- positive regulation of smooth muscle cell apoptotic process
- positive regulation of transcription by RNA polymerase II
- protein acetylation
- regulation of neural precursor cell proliferation
- regulation of reactive oxygen species metabolic process
- regulation of transcription by RNA polymerase II
- regulation of transcription initiation by RNA polymerase II
- response to fatty acid
- temperature homeostasis
Molecular functions
- beta-catenin binding
- chromatin binding
- chromatin DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- nucleic acid binding
- promoter-specific chromatin binding
- protein phosphatase 2A binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- ubiquitin protein ligase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Fork head domain
- Fork head domain conserved site 2
- FOXO protein, transactivation domain
- FOXO protein, KIX-binding domain
- Winged helix-like DNA-binding domain superfamily
- Winged helix DNA-binding domain superfamily
- Forkhead domain
- KIX-binding domain of forkhead box O, CR2
- Transactivation domain of FOXO protein family
- Forkhead box protein O1, forkhead domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of FOXO1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads FOXO1 as an antibody target. Whether an autoantibody or antibody against FOXO1 could matter depends on whether native FOXO1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
FOXO1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label FOXO1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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