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FOXO4 Gene

protein-coding   GIFtS: 61
GCID: GC0XP070316

Forkhead Box O4

(Previous names: myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila)...)
(Previous symbol: MLLT7)
  See FOXO4-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 O41 2     Fork Head Domain Transcription Factor AFX12 3
MLLT71 2 3 5     AFX2 3
AFX12 3 5     Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax (Drosophila)
Homolog); Translocated To, 71
Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog,
Drosophila); Translocated To, 71 2
     Forkhead Box Protein O42

External Ids:    HGNC: 71391   Entrez Gene: 43032   Ensembl: ENSG000001844817   OMIM: 3000335   UniProtKB: P981773   

Export aliases for FOXO4 gene to outside databases

Previous GC identifers: GC0XP070233 GC0XP064135


(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 FOXO4 Gene:
This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded
by this class are regulated by factors involved in growth and differentiation indicating they play a role in
these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax
gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript
variants encoding different isoforms have been found for this gene. (provided by RefSeq, Jan 2010)

GeneCards Summary for FOXO4 Gene:
FOXO4 (forkhead box O4) is a protein-coding gene. Diseases associated with FOXO4 include spinocerebellar ataxia type 3, and cutaneous fibrous histiocytoma. GO annotations related to this gene include transcription factor binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is FOXM1.

UniProtKB/Swiss-Prot: FOXO4_HUMAN, P98177
Function: Transcription factor involved in the regulation of the insulin signaling pathway. Binds to
insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and
suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative
regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by
activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher
proteasome activity

Gene Wiki entry for FOXO4 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 at NCBI GenBank:
NC_000023.10  NC_018934.2  NT_011651.18  
Regulatory elements:
   Regulatory transcription factor binding sites in the FOXO4 gene promoter:
         GR   Tal-1   GR-beta   E47   Evi-1   IRF-2   HFH-1   c-Myb   GR-alpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidFOXO4 promoter sequence
   Search Chromatin IP Primers for FOXO4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat FOXO4


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

Entrez Gene cytogenetic band: Xq13.1   Ensembl cytogenetic band:  Xq13.1   HGNC cytogenetic band: Xq13.1

FOXO4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FOXO4 gene location

GeneLoc information about chromosome X         GeneLoc Exon Structure

GeneLoc location for GC0XP070316:  view genomic region     (about GC identifiers)

Start:
70,315,999 bp from pter      End:
70,323,385 bp from pter
Size:
7,387 bases      Orientation:
plus 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: FOXO4_HUMAN, P98177 (See protein sequence)
Recommended Name: Forkhead box protein O4  
Size: 505 amino acids; 53684 Da
Subunit: Interacts with CREBBP/CBP, CTNNB1, MYOCD, SIRT1, SRF and YWHAZ. Acetylated by CREBBP/CBP and deacetylated
by SIRT1. Binding of YWHAZ inhibits DNA-binding. Interacts with USP7; the interaction is enhanced in presence of
hydrogen peroxide and occurs independently of TP53. Interacts with NLK, and this inhibits monoubiquitination and
transcriptional activity
2 PDB 3D structures from and Proteopedia for FOXO4:
1E17 (3D)        3L2C (3D)    
Secondary accessions: B7WPJ7 O43821 Q13720 Q3KPF1 Q8TDK9
Alternative splicing: 2 isoforms:  P98177-1   P98177-2   

Explore the universe of human proteins at neXtProt for FOXO4: NX_P98177

Explore proteomics data for FOXO4 at MOPED

Post-translational modifications: 

  • Acetylation by CREBBP/CBP, which is induced by peroxidase stress, inhibits transcriptional activity. Deacetylation
    by SIRT1 is NAD-dependent and stimulates transcriptional activity1
  • Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May
    be phosphorylated at multiple sites by NLK1
  • Monoubiquitinated; monoubiquitination is induced by oxidative stress and reduced by deacetylase inhibitors;
    results in its relocalization to the nucleus and its increased transcriptional activity. Deubiquitinated by USP7;
    deubiquitination is induced by oxidative stress; enhances its interaction with USP7 and consequently,
    deubiquitination; increases its translocation to the cytoplasm and inhibits its transcriptional activity.
    Hydrogene-peroxide-induced ubiquitination and USP7-mediated deubiquitination have no major effect on its protein
    stability1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See FOXO4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001164402.1  NP_005929.2  

    ENSEMBL proteins: 
     ENSP00000363377   ENSP00000342209  

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    Cloud-Clone Corp. Proteins for FOXO4

     
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    antibodies-online proteins for FOXO4 (2 products) 

     
    antibodies-online peptides for FOXO4

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    (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 P98177

    ProtoNet protein and cluster: P98177

    UniProtKB/Swiss-Prot: FOXO4_HUMAN, P98177
    Similarity: Contains 1 fork-head DNA-binding domain


    Find genes that share domains with FOXO4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: FOXO4_HUMAN, P98177
    Function: Transcription factor involved in the regulation of the insulin signaling pathway. Binds to
    insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and
    suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative
    regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by
    activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher
    proteasome activity

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677DNA binding IDA10783894
    GO:0003700sequence-specific DNA binding transcription factor activity IDA10783894
    GO:0005515protein binding IPI15126506
    GO:0008134transcription factor binding IPI16054032
    GO:0008301DNA binding, bending IBA--
         
    Find genes that share ontologies with FOXO4           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for FOXO4:
     Reduced beta-catenin activity  

         3 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Foxo4):
     mortality/aging  normal  tumorigenesis 

    Find genes that share phenotypes with FOXO4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for FOXO4: Foxo4tm1Kca Foxo4tm1.1Rdp

       genOway: Develop your customized and physiologically relevant rodent model for FOXO4

    miRNA
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    hsa-mir-615-3p (MIRT039705), hsa-mir-499a-5p (MIRT006698), hsa-mir-335-5p (MIRT018590)

    Block miRNA regulation of human, mouse, rat FOXO4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate FOXO4 (see all 76):
    hsa-miR-640 hsa-miR-1321 hsa-miR-193a-3p hsa-miR-605 hsa-miR-128 hsa-miR-637 hsa-miR-149 hsa-miR-508-5p
    SwitchGear 3'UTR luciferase reporter plasmidFOXO4 3' UTR sequence
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    Addgene plasmids for FOXO4 

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    (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
    FOXO4_HUMAN, P98177: Cytoplasm. Nucleus. Note=When phosphorylated, translocated from nucleus to cytoplasm.
    Dephosphorylation triggers nuclear translocation. Monoubiquitination increases nuclear localization. When
    deubiquitinated, translocated from nucleus to cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol5
    nucleus5
    cytoskeleton2
    extracellular1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus TAS--
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm IDA16964248
    GO:0005829cytosol TAS--

    Find genes that share ontologies with FOXO4           About GenesLikeMe


    (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 FOXO4 About   (see all 18)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1PI-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
    2Signaling 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
    3IL-9 Signaling Pathways
    IL-9 Signaling Pathways0.90
    IL-2 Signaling Pathways0.88
    IL-7 Signaling Pathways0.90
    IL-15 Signaling Pathways0.88
    IL-21 Signaling Pathways0.90
    IL-4 Signaling Pathways0.84
    Common Cytokine Receptor Gamma-Chain Family Signaling Pathways0.90
    4Downstream Signaling Events Of B Cell Receptor (BCR)
    Downstream Signaling Events Of B Cell Receptor (BCR)0.79
    Signaling by the B Cell Receptor (BCR)0.79
    5Signaling by GPCR
    Signal Transduction0.58


    Find genes that share SuperPaths with FOXO4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for FOXO4 (see all 7)
        IL-21 Signaling Pathways
    IL-2 Signaling Pathways
    IL-9 Signaling Pathways
    IL-4 Signaling Pathways
    IL-15 Signaling Pathways


    1 Cell Signaling Technology (CST) Pathway for FOXO4
        PI3K / Akt Signaling

    Selected BioSystems Pathways for FOXO4 (see all 8)
        AGE/RAGE pathway
    Signaling Pathways in Glioblastoma
    TGF-beta Receptor Signaling Pathway
    IL-6 Signaling Pathway
    Regulation of nuclear SMAD2/3 signaling


    2 Kegg Pathways  (Kegg details for FOXO4):
        Ras signaling pathway
    FoxO signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Array including FOXO4: 
              Angiogenic Growth Factors in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for FOXO4

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

    Selected Interacting proteins for FOXO4 (P981771, 2, 3 ENSP000003633774) via UniProtKB, MINT, STRING, and/or I2D (see all 61)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SIRT1Q96EB61, 3, ENSP000002120154EBI-4481939,EBI-1802965 I2D: score=1 STRING: ENSP00000212015
    YWHAZP631042, 3, ENSP000003095034MINT-8006602 MINT-8006595 I2D: score=4 STRING: ENSP00000309503
    OGTO152942, 3, ENSP000003628244MINT-7299691 I2D: score=1 STRING: ENSP00000362824
    SMAD3P840223, ENSP000003329734I2D: score=4 STRING: ENSP00000332973
    MDM2Q009873, ENSP000004172814I2D: score=1 STRING: ENSP00000417281
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 23):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006355regulation of transcription, DNA-templated IDA15126506
    GO:0006366transcription from RNA polymerase II promoter TAS10783894
    GO:0007050cell cycle arrest IDA10783894
    GO:0007095mitotic G2 DNA damage checkpoint IBA--
    GO:0007173epidermal growth factor receptor signaling pathway TAS--

    Find genes that share ontologies with FOXO4           About GenesLikeMe



    (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)
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    Browse Small Molecules at EMD Millipore
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    Browse Tocris compounds for FOXO4

    UniProtKB/Swiss-Prot: FOXO4_HUMAN, P98177
    Pharmaceutical: A constitutively active FOXO4 mutant where phosphorylation sites Thr-32, Ser-197 and Ser-262 have
    been mutated to alanine may have therapeutic potential in ERBB2/HER2-overexpressing cancers as it inhibits
    ERBB2-mediated cell survival, transformation and tumorigenicity

    1 HMDB Compound for FOXO4    About this table
    CompoundSynonyms CAS #PubMed Ids
    NAD3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)53-84-9--

    3 Novoseek inferred chemical compound relationships for FOXO4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    wortmannin 51.9 2 10518537 (2)
    phosphatidylinositol 50.8 1 10518537 (1)
    glycogen 24 1 16973122 (1)



    Find genes that share compounds with FOXO4           About GenesLikeMe



    (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, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for FOXO4 gene (2 alternative transcripts): 
    NM_001170931.1  NM_005938.3  

    Unigene Cluster for FOXO4:

    Forkhead box O4
    Hs.584654  [show with all ESTs]
    Unigene Representative Sequence: NM_005938
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000374259(uc004dyt.2 uc004dys.2) ENST00000466874 ENST00000341558
    ENST00000464598
    miRNA
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    hsa-miR-640 hsa-miR-1321 hsa-miR-193a-3p hsa-miR-605 hsa-miR-128 hsa-miR-637 hsa-miR-149 hsa-miR-508-5p
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      QuantiFast Probe-based Assays in human, mouse, rat FOXO4

    Additional mRNA sequence: 

    AF384029.1 AK300142.1 BC026735.1 BC106761.2 U10072.1 X93996.1 

    2 DOTS entries:

    DT.109928  DT.95141199 

    Selected AceView cDNA sequences (see all 57):

    AL532357 CR596165 CR620527 BM672472 BM724728 AL552503 CK430063 AW292413 
    BE732899 T54418 AW027741 CR595958 BQ278065 BQ021921 AL541001 BC026735 
    BP349083 AW075830 AL544994 BX402597 AI761711 BM985221 BE350669 AL575789 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for FOXO4    About this scheme

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


    ECgene alternative splicing isoforms for FOXO4

    (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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    FOXO4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TGCTAGATTG
    FOXO4 Expression
    About this image


    FOXO4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Inner Cell Mass (Early Embryonic Tissues)    fully expand to see all 2 entries
             Human embryonic stem cells (family)
     
     Blood (Hematopoietic System)
             Erythroblasts Hematopoietic Bone Marrow
     
     Placenta (Extraembryonic Tissues)
    FOXO4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    FOXO4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.584654

    UniProtKB/Swiss-Prot: FOXO4_HUMAN, P98177
    Tissue specificity: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform zeta is
    most abundant in the liver, kidney, and pancreas

        Pathway & Disease-focused RT2 Profiler PCR Array including FOXO4: 
              Angiogenic Growth Factors in human mouse rat

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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FOXO4

    (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)
    About This Section

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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for FOXO4 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Foxo41 , 5 forkhead box O41, 5 88.36(n)1
    88.69(a)1
      X (43.89 cM)5
    546011  NM_018789.21  NP_061259.11 
     1012545285 
    chicken
    (Gallus gallus)
    Aves FOXO41 forkhead box O4 60.19(n)
    59.72(a)
      428703  XM_426261.4  XP_426261.4 
    lizard
    (Anolis carolinensis)
    Reptilia FOXO46
    forkhead box O4
    53(a)
    1 ↔ 1
    GL343758.1(160087-175421)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia LOC1004928311 forkhead box protein O4-like 58.43(n)
    59.82(a)
      100492831  XM_004916822.1  XP_004916879.1 
    zebrafish
    (Danio rerio)
    Actinopterygii LOC5637191 forkhead box protein O4-like 58.46(n)
    57.11(a)
      563719  XM_687076.6  XP_692168.4 
    fruit fly
    (Drosophila melanogaster)
    Insecta foxo6
    forkhead box, sub-group O
    26(a)
    1 → many
    3R(9882690-9913700)
    worm
    (Caenorhabditis elegans)
    Secernentea daf-166
    Protein DAF-16, isoform h
    24(a)
    1 → many
    I(10750343-10776700) WBGene00000912
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes HCM16
    Forkhead transcription factor that drives S-phase ...
    12(a)
    1 → many
    III(229310-231004) YCR065W


    ENSEMBL Gene Tree for FOXO4 (if available)
    TreeFam Gene Tree for FOXO4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for FOXO4 gene
    FOXM12  FOXO62  FOXO32  FOXO12  
    4 SIMAP similar genes for FOXO4 using alignment to 1 protein entry:     FOXO4_HUMAN:
    FOXO6    DKFZp781A0677    FOXO1    FOXO3

    Find genes that share paralogs with FOXO4           About GenesLikeMe



    (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 FOXO4 (see all 132)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr X posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs59807401,2
    C--70314204(+) AGGAAA/GGAAAG 2 -- us2k1 trp30--------
    rs726288941,2
    C--70314657(+) ACCTCC/TTGGGT 2 -- us2k10--------
    rs582640361,2
    C--70319453(+) AACCA-/TTAAGC 2 -- int10--------
    rs1820333421,2
    --70321896(+) AGGAAA/GGAAGG 2 -- us2k10--------
    rs2001582191,2
    C--70321939(+) GAAGG-/AGGGAAG 2 -- us2k10--------
    rs59810701,2
    C,A,H--70322018(+) aagaaA/Ggaagg 2 -- us2k1 tfbs3 trp30--------
    rs2005806101,2
    --70322019(+) GAAAG-/AAAGGA 2 -- us2k10--------
    rs2016907081,2
    C--70322037(+) AAGAA-/GAAG  
            
    AAGGA
    2 -- us2k10--------
    rs1490578881,2
    C--70322166(+) GTTAGC/TGTCTT 2 -- us2k10--------
    rs59807411,2
    C,F,H--70322271(+) AATTTG/TCACAG 2 -- us2k112Minor allele frequency- T:0.17NS EA WA NA 1648

    HapMap Linkage Disequilibrium report for FOXO4 (70315999 - 70323385 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for FOXO4:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv33082CNV Loss17666407
    esv1584074OTHER Inversion17803354

    Locus Specific Mutation Databases (LSDB): FOXO4

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing FOXO4
    DNA2.0 Custom Variant and Variant Library Synthesis for FOXO4

    (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: 300033    OMIM disorders: --

    UniProtKB/Swiss-Prot: FOXO4_HUMAN, P98177
  • Note=A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23)
    with KMT2A/MLL1. The result is a rogue activator protein

  • 4 diseases for FOXO4:    
    About MalaCards
    spinocerebellar ataxia type 3    cutaneous fibrous histiocytoma    malignant fibroxanthoma    leukemia

    7 diseases from the University of Copenhagen DISEASES database for FOXO4:
    Malignant fibroxanthoma     Dermatofibrosarcoma     Cutaneous fibrous histiocytoma     Squamous cell carcinoma
    Fibrous histiocytoma     Melanoma     Leiomyosarcoma

    Find genes that share disorders with FOXO4           About GenesLikeMe

    3 Novoseek inferred disease relationships for FOXO4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    acute leukemia 33.6 3 9010221 (3)
    tumors 0 4 18648506 (2), 17599731 (1)
    cancer 0 7 15688030 (2), 11353388 (1), 9010221 (1)

    Genetic Association Database (GAD): FOXO4
    Human Genome Epidemiology (HuGE) Navigator: FOXO4 (2 documents)

    Export disorders for FOXO4 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 FOXO4 gene, integrated from 10 sources (see all 83):
    (articles sorted by number of sources associating them with FOXO4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. (PubMed id 7529552)1, 2, 3 Parry P.... Evans G. (Genes Chromosomes Cancer 1994)
    2. Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23). (PubMed id 9010221)1, 2, 9 Borkhardt A.... Lampert F. (Oncogene 1997)
    3. Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. (PubMed id 15688030)1, 2, 9 Yang H.... Lee M.-H. (Oncogene 2005)
    4. Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin. (PubMed id 16054032)1, 2, 9 Liu Z.-P.... Olson E.N. (Dev. Cell 2005)
    5. Solution structure of the DNA binding domain of the human forkhead transcription factor AFX (FOXO4). (PubMed id 11352721)1, 2, 9 Weigelt J.... Wikstrom M. (Biochemistry 2001)
    6. Regulation of intracellular localization and transcriptional activity of FOXO4 by protein kinase B through phosphorylation at the motif sites conserved among the FOXO family. (PubMed id 16272144)1, 2, 9 Matsuzaki H.... Kikkawa U. (J. Biochem. 2005)
    7. Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. (PubMed id 10518537)1, 2, 9 Takaishi H.... Nishizuka Y. (Proc. Natl. Acad. Sci. U.S.A. 1999)
    8. Oxidative stress-dependent regulation of Forkhead box O4 activity by nemo-like kinase. (PubMed id 20874444)1, 2 Szypowska A.A....Burgering B.M.T. (Antioxid. Redox Signal. 2011)
    9. Polymorphisms in FOXO gene family and association analysis with BMI. (PubMed id 16571842)1, 4 Kim J.R....Shin H.D. (Obesity (Silver Spring) 2006)
    10. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. (PubMed id 16964248)1, 2 van der Horst A.... Burgering B.M. (Nat. Cell Biol. 2006)

    (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: 4303 HGNC: 7139 AceView: MLLT7 Ensembl:ENSG00000184481 euGenes: HUgn4303
    ECgene: FOXO4 Kegg: 4303 H-InvDB: FOXO4

    (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 FOXO4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for FOXO4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for FOXO4 gene:
    Search GeneIP for patents involving FOXO4

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



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