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FOXO1 Gene

protein-coding   GIFtS: 63
GCID: GC13M041129

Forkhead Box O1

(Previous name: forkhead homolog in rhabdomyosarcoma)
(Previous symbols: FKHR, FOXO1A)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Forkhead Box O11 2     FKH12
FKHR1 2 3 5     Forkhead Box Protein O12
FOXO1A1 2 3 5     Forkhead, Drosophila, Homolog Of, In Rhabdomyosarcoma2
Forkhead Box Protein O1A2 3     Forkhead In Rhabdomyosarcoma3
Forkhead Homolog In Rhabdomyosarcoma1     

External Ids:    HGNC: 38191   Entrez Gene: 23082   Ensembl: ENSG000001509077   OMIM: 1365335   UniProtKB: Q127783   

Export aliases for FOXO1 gene to outside databases

Previous GC identifers: GC13M040028 GC13M021931


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for FOXO1 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)

GeneCards Summary for FOXO1 Gene:
FOXO1 (forkhead box O1) is a protein-coding gene. Diseases associated with FOXO1 include rhabdomyosarcoma 2, alveolar, and rhabdomyosarcoma. GO annotations related to this gene include DNA binding, bending and sequence-specific DNA binding. An important paralog of this gene is FOXM1.

UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778
Function: Transcription factor that is the main target of insulin signaling 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. Acts
syngernistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering
glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream
activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A to
activate the expression of genes such as IGFBP1, G6PC and PPCK1. Important regulator of cell death acting
downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose.
Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte
size and adipose tissue-specific gene expression in response to excessive calorie intake. Regulates the
transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells

Gene Wiki entry for FOXO1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000013.11  NC_018924.2  NT_024524.15  
Regulatory elements:
   Regulatory transcription factor binding sites in the FOXO1 gene promoter:
         COUP-TF1   COUP-TF   AP-1   COUP   HNF-4alpha1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): FOXO1 promoter sequence
   Search Chromatin IP Primers for FOXO1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat FOXO1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 13q14.1   Ensembl cytogenetic band:  13q14.11   HGNC cytogenetic band: 13q14.1

FOXO1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FOXO1 gene location

GeneLoc information about chromosome 13         GeneLoc Exon Structure

GeneLoc location for GC13M041129:  view genomic region     (about GC identifiers)

Start:
41,129,801 bp from pter      End:
41,240,734 bp from pter
Size:
110,934 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778 (See protein sequence)
Recommended Name: Forkhead box protein O1  
Size: 655 amino acids; 69662 Da
Subunit: Interacts with LRPPRC. Interacts with RUNX2; the interaction inhibits RUNX2 transcriptional activity and
mediates the IGF1/insulin-dependent BGLAP expression in osteoblasts Interacts with PPP2R1A; the interaction
regulates the dephosphorylation of FOXO1 at Thr-24 and Ser-256 leading to its nuclear import (By similarity).
Interacts with NLK. Interacts with SIRT1; the interaction results in the deacetylation of FOXO1 leading to
activation of FOXO1-mediated transcription of genes involved in DNA repair and stress resistance. Binds to CDK1.
Interacts with the 14-3-3 proteins, YWHAG and YWHAZ; the interactions require insulin-stimulated phosphorylation
on Thr-24, promote nuclear exit and loss of transcriptional activity. Interacts with SKP2; the interaction
ubiquitinates FOXO1 leading to its proteosomal degradation. The interaction requires the presence of KRIT1.
Interacts (via the C-terminal half) with ATF4 (via its DNA-binding domain); the interaction occurs in
osteoblasts, regulates glucose homeostasis via suppression of beta-cell proliferation and subsequent decrease in
insulin production. Interacts with PRMT1; the interaction methylates FOXO1, prevents PKB/AKT1 phosphorylation and
retains FOXO1 in the nucleus. Interacts with EP300 and CREBBP; the interactions acetylate FOXO1
3 PDB 3D structures from and Proteopedia for FOXO1:
3CO6 (3D)        3CO7 (3D)        3COA (3D)    
Secondary accessions: O43523 Q5VYC7 Q6NSK6

Explore the universe of human proteins at neXtProt for FOXO1: NX_Q12778

Explore proteomics data for FOXO1 at MOPED

Post-translational modifications: 

  • Phosphorylation by NLK promotes nuclear export and inhibits the transcriptional activity. In response to growth
    factors, phosphorylation on Thr-24, Ser-256 and Ser-322 by PKB/AKT1 promotes nuclear export and inactivation of
    transactivational activity. Phosphorylation on Thr-24 is required for binding 14-3-3 proteins. Phosphorylation of
    Ser-256 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-319, permitting
    phosphorylation of Ser-322 and Ser-325, probably by CDK1, leading to nuclear exclusion and loss of function.
    Stress signals, such as response to oxygen or nitric oxide, attenuate the PKB/AKT1-mediated phosphorylation
    leading to nuclear retention. Phosphorylation of Ser-329 is independent of IGF1 and leads to reduced function.
    Dephosphorylated on Thr-24 and Ser-256 by PP2A in beta-cells under oxidative stress leading to nuclear retention
    (By similarity). Phosphorylation of Ser-249 by CDK1 disrupts binding of 14-3-3 proteins leading to nuclear
    accumulation and has no effect on DNA-binding nor transcriptional activity. Phosphorylation by STK4/MST1 on
    Ser-212, upon oxidative stress, inhibits binding to 14-3-3 proteins and nuclear export1
  • Ubiquitinated by SRT2. Ubiquitination leads to proteasomal degradation1
  • Methylation inhibits AKT1-mediated phosphorylation at Ser-256 and is increased by oxidative stress (By similarity)1
  • Once in the nucleus, acetylated by CREBBP/EP300. Acetylation diminishes the interaction with target DNA and
    attenuates the transcriptional activity. It increases the phosphorylation at Ser-256. Deacetylation by SIRT1
    results in reactivation of the transcriptional activity. Oxidative stress by hydrogen peroxide treatment appears
    to promote deacetylation and uncoupling of insulin-induced phosphorylation. By contrast, resveratrol acts
    independently of acetylation1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See FOXO1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_002006.2  
    ENSEMBL proteins: 
     ENSP00000368880  
    Reactome Protein details: Q12778

    FOXO1 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant FOXO1 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for FOXO1
    OriGene Protein Over-expression Lysate for FOXO1
    OriGene MassSpec for FOXO1
    OriGene Custom Protein Services for FOXO1
    GenScript Custom Purified and Recombinant Proteins Services for FOXO1
    Novus Biologicals FOXO1 Proteins
    Novus Biologicals FOXO1 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for FOXO1

    FOXO1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of FOXO1
    R&D Systems Antibodies for FOXO1 (FoxO1/FKHR)
    Cell Signaling Technology (CST) Antibodies for FOXO1  (FOXO1A)
    OriGene Antibodies for FOXO1
    OriGene Custom Antibody Services for FOXO1
    Novus Biologicals FOXO1 Antibodies
    Abcam antibodies for FOXO1 (P98177, Q12778)
    Cloud-Clone Corp. Antibodies for FOXO1
    ThermoFisher Antibody for FOXO1
    LSBio Antibodies in human, mouse, rat for FOXO1

    FOXO1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for FOXO1
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for FOXO1
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for FOXO1
    Cloud-Clone Corp. CLIAs for FOXO1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    FOX: Forkhead boxes

    3 InterPro protein domains:
     IPR011991 WHTH_DNA-bd_dom
     IPR018122 TF_fork_head_CS
     IPR001766 TF_fork_head

    Graphical View of Domain Structure for InterPro Entry Q12778

    ProtoNet protein and cluster: Q12778

    UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778
    Similarity: Contains 1 fork-head DNA-binding domain


    FOXO1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
    About This Section

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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: FOXO1_HUMAN, Q12778
    Function: Transcription factor that is the main target of insulin signaling 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. Acts
    syngernistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering
    glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream
    activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A to
    activate the expression of genes such as IGFBP1, G6PC and PPCK1. Important regulator of cell death acting
    downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose.
    Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte
    size and adipose tissue-specific gene expression in response to excessive calorie intake. Regulates the
    transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells
    Induction: Expression is regulated by KRIT1. Levels of expression also regulated by FOXC1 which binds to a
    conserved element in the FOXO1 promoter

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001078RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription IEA--
    GO:0003677DNA binding ----
    GO:0003682chromatin binding ISS--
    GO:0003700sequence-specific DNA binding transcription factor activity ----
    GO:0005515protein binding IPI11237865
         
    FOXO1 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for FOXO1:
     Decreased viability with carbo  Increased cell death in breast 

         Selected MGI mutant phenotypes (inferred from 13 alleles(MGI details for Foxo1) (see all 21):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  craniofacial 
     digestive/alimentary  embryogenesis  endocrine/exocrine gland  growth/size/body  hematopoietic system 
     homeostasis/metabolism  immune system  integument  limbs/digits/tail  liver/biliary system 

    FOXO1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for FOXO1: Foxo1tm1.1Mrc Foxo1tm1.1Rdp Foxo1tm1Tf

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for FOXO1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for FOXO1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for FOXO1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for FOXO1

    Transcription Factor Targeting: 
    Selected GeneGlobe predicted Target genes for FOXO1 (see all 686):
    A1CF,  A4GNT,  AADACL2,  ABHD3,  ABT1,  ACAT1,  ACE2,  ACO1,  ACPP,  ACSF2

    Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer 
                                          Consensus sequence:  CTGTTTAC 

    miRNA
    Products:
        
    miRTarBase miRNAs that target FOXO1:
    hsa-mir-153-3p (MIRT003299), hsa-mir-223-3p (MIRT006733), hsa-mir-182-5p (MIRT001086), hsa-mir-9-5p (MIRT003300), hsa-mir-183-5p (MIRT003298), hsa-mir-186-5p (MIRT003297), hsa-mir-132-3p (MIRT045840), hsa-mir-96-5p (MIRT001087), hsa-mir-15a-5p (MIRT051345), hsa-mir-196a-5p (MIRT048219), hsa-mir-335-5p (MIRT016933), hsa-mir-106b-3p (MIRT038575), hsa-mir-98-5p (MIRT027447), hsa-mir-27a-3p (MIRT001088)

    Block miRNA regulation of human, mouse, rat FOXO1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate FOXO1 (see all 114):
    hsa-miR-411* hsa-miR-26a-2* hsa-miR-3607-3p hsa-miR-300 hsa-miR-411 hsa-miR-15a hsa-miR-128 hsa-miR-578
    SwitchGear 3'UTR luciferase reporter plasmidFOXO1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for FOXO1
    Predesigned siRNA for gene silencing in human, mouse, rat FOXO1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for FOXO1

    Clone
    Products:
         
    OriGene clones in human, mouse for FOXO1 (see all 6)
    OriGene ORF clones in mouse, rat for FOXO1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: FOXO1 (NM_002015)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for FOXO1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FOXO1

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for FOXO1
    Browse ESI BIO Cell Lines and PureStem Progenitors for FOXO1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FOXO1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    FOXO1_HUMAN, Q12778: Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and nucleus. Largely nuclear in
    unstimulated cells. In osteoblasts, colocalizes with ATF4 and RUNX2 in the nucleus (By similarity).
    Insulin-induced phosphorylation at Ser-256 by PKB/AKT1 leads, via stimulation of Thr-24 phosphorylation, to
    binding of 14-3-3 proteins and nuclear export to the cytoplasm where it is degraded by the ubiquitin-proteosomal
    pathway. Phosphorylation at Ser-249 by CDK1 disrupts binding of 14-3-3 proteins and promotes nuclear
    accumulation. Phosphorylation by NLK results in nuclear export. Translocates to the nucleus upon oxidative
    stress-induced phosphorylation at Ser-212 by STK4/MST1. SGK1-mediated phosphorylation also results in nuclear
    translocation. Retained in the nucleus under stress stimuli including oxidative stress, nutrient deprivation or
    nitric oxide. Retained in the nucleus on methylation
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol4
    mitochondrion4
    peroxisome2
    cytoskeleton1
    endoplasmic reticulum1
    extracellular1
    plasma membrane1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA11311120
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm IDA11237865
    GO:0005739mitochondrion ISS--
    GO:0005829cytosol TAS--

    FOXO1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for FOXO1 About   (see all 46)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1IL-9 Signaling Pathways
    IL-9 Signaling Pathways0.90
    IL-15 Signaling Pathways0.88
    IL-7 Signaling Pathways0.90
    IL-4 Signaling Pathways0.84
    IL-21 Signaling Pathways0.90
    IL-7 Signaling Pathway0.40
    Common Cytokine Receptor Gamma-Chain Family Signaling Pathways0.90
    Development Thrombopoietin regulated cell processes0.38
    2Immune response IL 23 signaling pathway
    Development Angiopoietin Tie2 signaling0.38
    Angiopoietin receptor Tie2-mediated signaling0.32
    Angiopoietin-TIE2 Signaling0.36
    3Glioma
    Prostate cancer0.39
    Signaling Pathways in Glioblastoma0.36
    4PI-3K cascade
    PI3K/AKT activation0.93
    PI3K events in ERBB4 signaling0.88
    GAB1 signalosome0.93
    Role of LAT2/NTAL/LAB on calcium mobilization0.80
    Constitutive PI3K/AKT Signaling in Cancer0.88
    Signaling by SCF-KIT0.72
    PIP3 activates AKT signaling0.88
    Signaling by ERBB40.66
    5Signaling by FGFR
    Signaling by FGFR0.91
    DAP12 interactions0.89
    Signaling by FGFR in disease0.91
    Signaling by PDGF0.87
    Downstream signaling of activated FGFR0.91
    Signaling by EGFR0.83
    Downstream signal transduction0.90
    Signaling by EGFR in Cancer0.82

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for FOXO1 (see all 11)
        IL-21 Signaling Pathways
    IL-2 Signaling Pathways
    IL-4 Signaling Pathways
    Adipocytokines & Insulin Signaling
    Akt Signaling Pathway

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for FOXO1 (see all 6)
        DHA Signaling
    Molecular Mechanisms of Cancer
    ErbB Family Pathway
    Glioblastoma Multiforme
    Akt Signaling

    1 Cell Signaling Technology (CST) Pathway for FOXO1
        PI3K / Akt Signaling

    2 GeneGo (Thomson Reuters) Pathways for FOXO1
        Development Thrombopoietin-regulated cell processes
    Development Angiopoietin - Tie2 signaling

    Selected BioSystems Pathways for FOXO1 (see all 24)
        EGFR1 Signaling Pathway
    Adipogenesis
    Insulin Signaling
    ErbB signaling pathway
    Integrated Breast Cancer Pathway

    4 Reactome Pathways for FOXO1
        Regulation of gene expression in beta cells
    AKT phosphorylates targets in the nucleus
    AKT-mediated inactivation of FOXO1A
    Constitutive PI3K/AKT Signaling in Cancer


    Selected Kegg Pathways  (Kegg details for FOXO1) (see all 6):
        FoxO signaling pathway
    Insulin signaling pathway
    Thyroid hormone signaling pathway
    Pathways in cancer
    Transcriptional misregulation in cancer


    FOXO1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including FOXO1 (see all 7): 
              PI3K-AKT Signaling Pathway in human mouse rat
              Transcription Factors in human mouse rat
              Skeletal Muscle: Myogenesis & Myopathy in human mouse rat
              Prostate Cancer in human mouse rat
              Apoptosis 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for FOXO1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for FOXO1 (Q127781, 2, 3 ENSP000003688804) via UniProtKB, MINT, STRING, and/or I2D (see all 112)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SIRT1Q96EB61, 3, ENSP000002120154EBI-1108782,EBI-1802965 I2D: score=4 STRING: ENSP00000212015
    CDK1P064931, 3EBI-1108782,EBI-444308 I2D: score=1 
    YWHAZP631042, 3, ENSP000003095034MINT-8005539 MINT-8005546 I2D: score=5 STRING: ENSP00000309503
    CREBBPQ927931, 3, ENSP000002623674EBI-1108782,EBI-81215 I2D: score=4 STRING: ENSP00000262367
    ESR1P033721, 3, ENSP000002062494EBI-1108782,EBI-78473 I2D: score=4 STRING: ENSP00000206249
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 34):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001568blood vessel development IBA--
    GO:0001659temperature homeostasis ISS--
    GO:0001678cellular glucose homeostasis ISS--
    GO:0006355regulation of transcription, DNA-templated ----
    GO:0006357regulation of transcription from RNA polymerase II promoter ----

    FOXO1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for FOXO1

    Selected Novoseek inferred chemical compound relationships for FOXO1 gene (see all 21)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    ly294002 69 9 11030146 (1), 17408630 (1), 16133873 (1), 11593406 (1) (see all 6)
    phosphatidylinositol 67.3 16 11672436 (1), 15778376 (1), 17202144 (1), 12606579 (1) (see all 9)
    glycogen 51.5 10 15494423 (1), 15574783 (1), 12702569 (1), 16973122 (1) (see all 10)
    phosphoenolpyruvate 50.9 1 10913147 (1)
    phosphoinositide 44.9 2 12150827 (1), 17986386 (1)
    rapamycin 42.1 4 15494423 (1), 12782577 (1), 17077083 (1), 18202777 (1)
    leptomycin b 36.2 2 16133873 (1)
    threonine 33.8 6 12359217 (1), 13679577 (1), 11733864 (1), 18211894 (1)
    glucose 24.3 14 19141580 (3), 10960473 (2), 13679577 (1), 16670091 (1) (see all 8)
    serine 24 5 13679577 (1), 11733864 (1), 18211894 (1)



    FOXO1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for FOXO1 gene: 
    NM_002015.3  

    Unigene Cluster for FOXO1:

    Forkhead box O1
    Hs.370666  [show with all ESTs]
    Unigene Representative Sequence: NM_002015
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000379561(uc010acc.1 uc001uxl.4) ENST00000473775
    miRNA
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    Additional mRNA sequence: 

    AF032885.1 AK310511.1 BC021981.2 BC070065.1 BT007455.1 BX648278.1 HQ824715.1 U02310.1 
    U36922.1 

    7 DOTS entries:

    DT.317826  DT.92454302  DT.40105832  DT.120780767  DT.95151680  DT.101958152  DT.92454306 

    Selected AceView cDNA sequences (see all 263):

    BC021981 CA413963 AI246476 AW072902 CA309741 CB069714 CA503017 AI474214 
    AI804396 T85080 AI813640 AA172023 BF733006 BF439016 U36922 AI188507 
    BQ941361 AA306562 AI494178 BF057343 AW274481 AI346535 CA437000 AA130464 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for FOXO1    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6
    SP1:        -     -     -                           
    SP2:              -                                 
    SP3:              -     -                           
    SP4:                    -                           


    ECgene alternative splicing isoforms for FOXO1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    FOXO1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CCTCCTGCAT
    FOXO1 Expression
    About this image


    FOXO1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 10) fully expand
     
     Bone (Muscoskeletal System)    fully expand to see all 4 entries
             Bone marrow-derived mesenchymal stem cells
             HyStem+TGFbeta3+GDF5-induced SK11 cells
     
     Ovary (Reproductive System)    fully expand to see all 3 entries
             Granulosa Cells Primary Follicle
     
     Brain (Nervous System)    fully expand to see all 3 entries
             Thalamus
     
     Inner Cell Mass (Early Embryonic Tissues)    fully expand to see all 2 entries
             Human embryonic stem cells (family)
     
     Gonad
             Primary Oocyte Primary Follicle
    FOXO1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    FOXO1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.370666

    UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778
    Tissue specificity: Ubiquitous

        Pathway & Disease-focused RT2 Profiler PCR Arrays including FOXO1 (see all 7): 
              PI3K-AKT Signaling Pathway in human mouse rat
              Transcription Factors in human mouse rat
              Skeletal Muscle: Myogenesis & Myopathy in human mouse rat
              Prostate Cancer in human mouse rat
              Apoptosis 384HT in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for FOXO1 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Foxo11 , 5 forkhead box O11, 5 89.21(n)1
    92.91(a)1
      3 (23.19 cM)5
    564581  NM_019739.31  NP_062713.21 
     522683375 
    chicken
    (Gallus gallus)
    Aves FOXO11 forkhead box O1 77.85(n)
    77.48(a)
      374231  NM_204328.1  NP_989659.1 
    lizard
    (Anolis carolinensis)
    Reptilia FOXO16
    forkhead box O1
    69(a)
    1 ↔ 1
    1(132471532-132519420)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia Str.146252 Transcribed sequence with weak similarity to protein more 82.1(n)    BX702088.1 
    zebrafish
    (Danio rerio)
    Actinopterygii foxo1a1 forkhead box O1 a 64.67(n)
    63.95(a)
      768121  NM_001077257.2  NP_001070725.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta foxo6
    forkhead box, sub-group O
    30(a)
    1 → many
    3R(9882690-9913700)
    worm
    (Caenorhabditis elegans)
    Secernentea daf-166
    Protein DAF-16, isoform h
    30(a)
    1 → many
    I(10750343-10776700) WBGene00000912
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes HCM16
    Forkhead transcription factor that drives S-phase ...
    16(a)
    1 → many
    III(229310-231004) YCR065W


    ENSEMBL Gene Tree for FOXO1 (if available)
    TreeFam Gene Tree for FOXO1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for FOXO1 gene
    FOXM12  FOXO62  FOXO42  FOXO32  
    3 SIMAP similar genes for FOXO1 using alignment to 2 protein entries:     FOXO1_HUMAN (see all proteins):
    DKFZp781A0677    FOXO3    FOXO4

    FOXO1 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for FOXO1
    PGOHUM00000235489


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for FOXO1 (see all 2128)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 13 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs720082451,2
    C--21999943(+) GCTTA-/AAAA  
      A
    /TAAA
    AAAAA
    1 -- int10--------
    rs113449391,2
    C,F--22029946(+) ATACT-/A/AAAAA
    /AAAAAAAAA
    AAAAA
    2 -- int1 cds1 trp32NA 4
    rs740445321,2
    C,F--22074579(+) CCTCAG/AACATC 1 -- ds50012Minor allele frequency- A:0.15WA 120
    rs762126941,2
    C,F--22074827(+) AGTAAT/CTACTG 1 -- ds50011Minor allele frequency- C:0.05WA 118
    rs1873818981,2
    C--22074836(+) TGAACC/TGGATG 1 -- ds50010--------
    rs95770651,2
    C,F,A,H--22074921(+) ACTATA/GGTTTG 1 -- ds500115Minor allele frequency- G:0.06NS EA NA WA 1864
    rs342412431,2
    C,F--22075113(-) GCCATA/GAATGT 1 -- ut312Minor allele frequency- G:0.00NA 4
    rs1834082691,2
    --22075139(+) CAAAGA/GTTGTT 1 -- ut310--------
    rs1866128601,2
    --22075228(+) ACTCGA/GGTAGC 1 -- ut310--------
    rs1445737091,2
    C--22075234(+) GTAGCG/TAAATG 1 -- ut310--------

    HapMap Linkage Disequilibrium report for FOXO1 (41129801 - 41240734 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for FOXO1:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2747290CNV Deletion23290073
    nsv525547CNV Loss19592680

    Site Specific Mutation Identification with PCR Assays
    2 Copy Number PCR Panels containing FOXO1:
    Oncogenes & Tumor Suppressor Genes 384HC
    Gastric Cancer
    SeqTarget long-range PCR primers for resequencing FOXO1
    DNA2.0 Custom Variant and Variant Library Synthesis for FOXO1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 136533    OMIM disorders: --

    UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778
  • Rhabdomyosarcoma 2 (RMS2) [MIM:268220]: A form of rhabdomyosarcoma, a highly malignant tumor of striated
    muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines.
    Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It
    occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. Note=The gene
    represented in this entry may be involved in disease pathogenesis. Chromosomal aberrations involving FOXO1 are
    found in rhabdomyosarcoma. Translocation (2;13)(q35;q14) with PAX3 and translocation t(1;13)(p36;q14) with PAX7.
    The resulting protein is a transcriptional activator

  • Selected diseases for FOXO1 (see all 72):    
    About MalaCards
    rhabdomyosarcoma 2, alveolar    rhabdomyosarcoma    botryoid rhabdomyosarcoma    alveolar rhabdomyosarcoma
    embryonal rhabdomyosarcoma    nonalcoholic steatohepatitis    nephroblastoma    hyperinsulinism
    dwarfism    premature ovarian failure    glucose intolerance    clear cell renal cell carcinoma
    soft tissue sarcoma    insulin resistance    keratoconus    autism spectrum disorder
    acne    leiomyoma    glioblastoma multiforme    renal cell carcinoma

    4 diseases from the University of Copenhagen DISEASES database for FOXO1:
    Rhabdomyosarcoma     Diabetes mellitus     Hyperglycemia     Muscular atrophy

    FOXO1 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for FOXO1 gene (see all 19)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    rhabdomyosarcoma alveolar 92.2 20 11171995 (2), 7630639 (1), 8875708 (1), 8889501 (1) (see all 18)
    muscle cancer 87.4 1 16140913 (1)
    rhabdomyosarcoma 74.1 14 11672436 (1), 12196101 (1), 12456685 (1), 19408047 (1) (see all 10)
    sarcoma 38.9 5 19408047 (2), 18303411 (1)
    tumors 32.4 21 12351634 (2), 19704258 (1), 8634710 (1), 15688409 (1) (see all 18)
    childhood cancer 28 2 10700864 (1), 15184910 (1)
    hyperinsulinemia 24.4 4 17408630 (1), 19563779 (1), 16670091 (1), 17317207 (1)
    insulin resistance 23.7 8 19490822 (2), 10912522 (1), 15910615 (1), 16041833 (1) (see all 7)
    fatty liver 19.5 1 17408630 (1)
    insulin sensitivity 15.5 4 16670091 (1), 16041833 (1), 17317207 (1)

    Genetic Association Database (GAD): FOXO1
    Human Genome Epidemiology (HuGE) Navigator: FOXO1 (16 documents)

    Export disorders for FOXO1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for FOXO1 gene, integrated from 10 sources (see all 457):
    (articles sorted by number of sources associating them with FOXO1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The DNA sequence and analysis of human chromosome 13. (PubMed id 15057823)1, 2, 3 Dunham A.... Ross M.T. (Nature 2004)
    2. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. (PubMed id 8275086)1, 2, 3 Galili N.... Barr F.G. (Nat. Genet. 1993)
    3. Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding. (PubMed id 12228231)1, 2, 9 Zhang X.... Unterman T.G. (J. Biol. Chem. 2002)
    4. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. (PubMed id 9479491)1, 2, 9 Anderson M.J.... Arden K.C. (Genomics 1998)
    5. The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. (PubMed id 15890677)1, 2, 9 Perrot V. and Rechler M.M. (Mol. Endocrinol. 2005)
    6. Association of common genetic variation in the FOXO1 gene with beta-cell dysfunction, impaired glucose tolerance, and type 2 diabetes. (PubMed id 19141580)1, 4, 9 MA1ssig K....HAoring H.U. (J. Clin. Endocrinol. Metab. 2009)
    7. Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. (PubMed id 18951090)1, 2, 9 Yamagata K.... Fukamizu A. (Mol. Cell 2008)
    8. Analysis of FOXO1A as a candidate gene for type 2 diabetes. (PubMed id 16497530)1, 4, 9 Karim M.A....Elbein S.C. (Mol. Genet. Metab. 2006)
    9. Two novel phosphorylation sites on FKHR that are critical for its nuclear exclusion. (PubMed id 11980723)1, 2, 9 Rena G.... Cohen P. (EMBO J. 2002)
    10. Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification. (PubMed id 18786403)1, 2, 9 Brent M.M.... Marmorstein R. (Structure 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2308 HGNC: 3819 AceView: FOXO1A Ensembl:ENSG00000150907 euGenes: HUgn2308
    ECgene: FOXO1 Kegg: 2308 H-InvDB: FOXO1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for FOXO1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for FOXO1 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for FOXO1 gene:
    Search GeneIP for patents involving FOXO1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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