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    FOXO3 forkhead box O3 [ Homo sapiens (human) ]

    Gene ID: 2309, updated on 13-May-2024

    Summary

    Official Symbol
    FOXO3provided by HGNC
    Official Full Name
    forkhead box O3provided by HGNC
    Primary source
    HGNC:HGNC:3821
    See related
    Ensembl:ENSG00000118689 MIM:602681; AllianceGenome:HGNC:3821
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FOXO2; AF6q21; FKHRL1; FOXO3A; FKHRL1P2
    Summary
    This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in fat (RPKM 14.1), bone marrow (RPKM 13.9) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See FOXO3 in Genome Data Viewer
    Location:
    6q21
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (108559825..108684774)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (109737167..109862124)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (108881028..109005977)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene AFG1 like ATPase Neighboring gene uncharacterized LOC124901370 Neighboring gene uncharacterized LOC124901372 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17451 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24914 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17452 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17453 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17454 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:108882597-108883097 Neighboring gene Sharpr-MPRA regulatory region 14072 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24915 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:108908380-108908581 Neighboring gene OCT4 hESC enhancer GRCh37_chr6:108960200-108960701 Neighboring gene Sharpr-MPRA regulatory region 11562 Neighboring gene SUMO2 pseudogene 8 Neighboring gene MPRA-validated peak6015 silencer Neighboring gene Sharpr-MPRA regulatory region 11560 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:109019778-109020977 Neighboring gene Sharpr-MPRA regulatory region 15105 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:109051727-109052654 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:109052989-109053781 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:109053782-109054573 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:109057555-109058224 Neighboring gene uncharacterized LOC107986629 Neighboring gene long intergenic non-protein coding RNA 222

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3.
    EBI GWAS Catalog
    Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.
    EBI GWAS Catalog
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of forkhead box O3 (FOXO3) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat expression in Jurkat T cells increases the amount and the translocation of FOXO3a from the cytoplasm to the nucleus, indicating that FOXO3a is no longer phosphorylated PubMed
    Vpr vpr HIV-1 Vpr inhibits insulin-induced association of 14-3-3 and Foxo3a in HeLa cells PubMed
    vpr HIV-1 Vpr inhibits insulin- and Akt-induced cytoplasmic translocation of Foxo3a, a subtype of the forkhead transcription factors PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC12739, MGC31925, DKFZp781A0677

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription activator activity, RNA polymerase II-specific ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
     
    enables DNA-binding transcription repressor activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables beta-catenin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables chromatin DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables mitochondrial transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables transcription cis-regulatory region binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables transcription coregulator binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in DNA damage response, signal transduction by p53 class mediator IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in antral ovarian follicle growth IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in brain morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in canonical Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to amyloid-beta IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to corticosterone stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to glucose starvation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to glucose stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to nerve growth factor stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to oxidative stress ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in extrinsic apoptotic signaling pathway in absence of ligand IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in initiation of primordial ovarian follicle growth IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in mitochondrial transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in neuronal stem cell population maintenance IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in oocyte maturation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in ovulation from ovarian follicle IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of autophagy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of endothelial cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within positive regulation of erythrocyte differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of hydrogen peroxide-mediated programmed cell death IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of miRNA transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of muscle atrophy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of neuron apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of reactive oxygen species biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of regulatory T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of neural precursor cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of translation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to dexamethasone IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to fatty acid ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to starvation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to water-immersion restraint stress IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to xenobiotic stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in tumor necrosis factor-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of RNA polymerase II transcription repressor complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of chromatin ISA
    Inferred from Sequence Alignment
    more info
     
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    colocalizes_with mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    colocalizes_with mitochondrial matrix IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in mitochondrial outer membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    colocalizes_with mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    forkhead box protein O3
    Names
    FOXO3A-
    forkhead box O3A
    forkhead homolog (rhabdomyosarcoma) like 1
    forkhead in rhabdomyosarcoma-like 1
    forkhead, Drosophila, homolog of, in rhabdomyosarcoma-like 1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001415139.1NP_001402068.1  forkhead box protein O3 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
    2. NM_001415140.1NP_001402069.1  forkhead box protein O3 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
    3. NM_001415141.1NP_001402070.1  forkhead box protein O3 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
    4. NM_001415142.1NP_001402071.1  forkhead box protein O3 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
    5. NM_001415144.1NP_001402073.1  forkhead box protein O3 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509
      UniProtKB/TrEMBL
      A0A856PRE8
    6. NM_001415145.1NP_001402074.1  forkhead box protein O3 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon relative to variant 1. The encoded isoform (4, also known as FOXO3A-S) has a shorter N-terminus compared to isoform 1. A SNP in the 5' UTR of this variant, rs9400239, has been associated with human longevity (PMID:36617632).
      Source sequence(s)
      AL096818, AL365509
      UniProtKB/TrEMBL
      A0A856PRE8
      Related
      ENSP00000446316.1, ENST00000540898.1
    7. NM_001415146.1NP_001402075.1  forkhead box protein O3 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
      UniProtKB/TrEMBL
      A0A856PRE8
    8. NM_001415147.1NP_001402076.1  forkhead box protein O3 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
      UniProtKB/TrEMBL
      A0A856PRE8
    9. NM_001415148.1NP_001402077.1  forkhead box protein O3 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
      UniProtKB/TrEMBL
      A0A856PRE8
    10. NM_001415149.1NP_001402078.1  forkhead box protein O3 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
      UniProtKB/TrEMBL
      A0A856PRE8
    11. NM_001415150.1NP_001402079.1  forkhead box protein O3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AL096818, AL365509, AL391646
    12. NM_001455.4NP_001446.1  forkhead box protein O3 isoform 1

      See identical proteins and their annotated locations for NP_001446.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' end and represents the longer transcript compared to variant 2. Both variants encode the same protein.
      Source sequence(s)
      AF032886, AK024103, AL096818, AL365509, CA389775
      Consensus CDS
      CCDS5068.1
      UniProtKB/Swiss-Prot
      B4DVZ6, E1P5E6, O15171, O43524, Q5T2I7, Q9BZ04
      Related
      ENSP00000385824.1, ENST00000406360.2
      Conserved Domains (3) summary
      cd00059
      Location:157237
      FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
      pfam16675
      Location:433508
      FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
      pfam16676
      Location:606644
      FOXO-TAD; Transactivation domain of FOXO protein family
    13. NM_201559.3NP_963853.1  forkhead box protein O3 isoform 1

      See identical proteins and their annotated locations for NP_963853.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' end compared to variant 1. Both variants encode the same protein.
      Source sequence(s)
      AK024103, AL096818, AL365509, BC020227, CD101760
      Consensus CDS
      CCDS5068.1
      UniProtKB/Swiss-Prot
      B4DVZ6, E1P5E6, O15171, O43524, Q5T2I7, Q9BZ04
      Related
      ENSP00000339527.6, ENST00000343882.10
      Conserved Domains (3) summary
      cd00059
      Location:157237
      FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
      pfam16675
      Location:433508
      FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
      pfam16676
      Location:606644
      FOXO-TAD; Transactivation domain of FOXO protein family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      108559825..108684774
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010585.2XP_016866074.1  forkhead box protein O3 isoform X1

      UniProtKB/TrEMBL
      Q68DV3
      Conserved Domains (3) summary
      pfam16675
      Location:244319
      FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
      pfam16676
      Location:417455
      FOXO-TAD; Transactivation domain of FOXO protein family
      cl00061
      Location:1750
      FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
    2. XM_017010586.2XP_016866075.1  forkhead box protein O3 isoform X2

      UniProtKB/TrEMBL
      A0A856PRE8, Q68DV3
      Conserved Domains (3) summary
      pfam16675
      Location:213287
      FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
      pfam16676
      Location:386424
      FOXO-TAD; Transactivation domain of FOXO protein family
      cl00061
      Location:125
      FH_FOX; Forkhead (FH) domain found in Forkhead box (FOX) family of transcription factors and similar proteins

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      109737167..109862124
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054354806.1XP_054210781.1  forkhead box protein O3 isoform X1