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FOXO3 forkhead box O3 [ Homo sapiens (human) ]

Gene ID: 2309, updated on 4-Jan-2025

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
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Genomic context

See FOXO3 in Genome Data Viewer
Location:
6q21
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (108559825..108684774)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (109737167..109862124)
RS_2024_09 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: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 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
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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

General gene information

Clone Names

  • MGC12739, MGC31925, DKFZp781A0677

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding PubMed 
enables DNA-binding transcription activator activity, RNA polymerase II-specific  
enables DNA-binding transcription factor activity PubMed 
enables DNA-binding transcription factor activity, RNA polymerase II-specific  
enables DNA-binding transcription factor activity, RNA polymerase II-specific  
enables DNA-binding transcription repressor activity, RNA polymerase II-specific PubMed 
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding  
enables beta-catenin binding PubMed 
enables chromatin DNA binding  
enables mitochondrial transcription factor activity PubMed 
enables protein binding PubMed 
enables protein kinase binding PubMed 
enables sequence-specific DNA binding PubMed 
enables sequence-specific double-stranded DNA binding PubMed 
enables transcription cis-regulatory region binding  
enables transcription coregulator binding  
Items 1 - 25 of 45
Process Evidence Code Pubs
involved_in DNA damage response, signal transduction by p53 class mediator  
involved_in antral ovarian follicle growth  
involved_in brain morphogenesis  
involved_in canonical Wnt signaling pathway  
involved_in cellular response to amyloid-beta  
involved_in cellular response to corticosterone stimulus  
involved_in cellular response to glucose starvation PubMed 
involved_in cellular response to glucose stimulus  
involved_in cellular response to hypoxia  
involved_in cellular response to nerve growth factor stimulus  
involved_in cellular response to oxidative stress  
involved_in extrinsic apoptotic signaling pathway in absence of ligand  
involved_in initiation of primordial ovarian follicle growth  
involved_in mitochondrial transcription PubMed 
involved_in negative regulation of canonical Wnt signaling pathway  
involved_in negative regulation of cell migration PubMed 
involved_in negative regulation of neuron differentiation  
involved_in negative regulation of transcription by RNA polymerase II PubMed 
involved_in negative regulation of transcription by RNA polymerase II PubMed 
involved_in neuronal stem cell population maintenance  
involved_in oocyte maturation  
involved_in ovulation from ovarian follicle  
involved_in positive regulation of DNA-templated transcription PubMed 
involved_in positive regulation of apoptotic process PubMed 
involved_in positive regulation of autophagy  
involved_in positive regulation of endothelial cell apoptotic process  
acts_upstream_of_or_within positive regulation of erythrocyte differentiation PubMed 
involved_in positive regulation of hydrogen peroxide-mediated programmed cell death  
involved_in positive regulation of miRNA transcription  
involved_in positive regulation of muscle atrophy  
involved_in positive regulation of neuron apoptotic process PubMed 
involved_in positive regulation of reactive oxygen species biosynthetic process  
involved_in positive regulation of regulatory T cell differentiation PubMed 
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II PubMed 
involved_in positive regulation of transcription by RNA polymerase II PubMed 
involved_in regulation of neural precursor cell proliferation  
involved_in regulation of transcription by RNA polymerase II  
involved_in regulation of transcription by RNA polymerase II  
involved_in regulation of translation PubMed 
involved_in response to dexamethasone  
involved_in response to fatty acid  
involved_in response to starvation  
involved_in response to water-immersion restraint stress  
involved_in response to xenobiotic stimulus  
involved_in tumor necrosis factor-mediated signaling pathway PubMed 
Items 1 - 25 of 45
Component Evidence Code Pubs
part_of RNA polymerase II transcription repressor complex PubMed 
located_in chromatin  
located_in cytoplasm PubMed 
located_in cytosol PubMed 
located_in cytosol  
colocalizes_with mitochondrial matrix  
colocalizes_with mitochondrial matrix PubMed 
located_in mitochondrial outer membrane PubMed 
colocalizes_with mitochondrion PubMed 
located_in nucleoplasm  
located_in nucleoplasm  
is_active_in nucleus  
located_in nucleus PubMed 
located_in nucleus PubMed 
part_of protein-containing complex 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
    UniProtKB/TrEMBL
    Q68DV3
  2. NM_001415140.1NP_001402069.1  forkhead box protein O3 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL096818, AL365509, AL391646
    UniProtKB/TrEMBL
    Q68DV3
  3. NM_001415141.1NP_001402070.1  forkhead box protein O3 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL096818, AL365509, AL391646
    UniProtKB/TrEMBL
    Q68DV3
  4. NM_001415142.1NP_001402071.1  forkhead box protein O3 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL096818, AL365509, AL391646
    UniProtKB/TrEMBL
    Q68DV3
  5. NM_001415144.1NP_001402073.1  forkhead box protein O3 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL096818, AL365509
    UniProtKB/TrEMBL
    A0A856PRE8, Q68DV3
  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, Q68DV3
    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, Q68DV3
  8. NM_001415147.1NP_001402076.1  forkhead box protein O3 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL096818, AL365509, AL391646
    UniProtKB/TrEMBL
    A0A856PRE8, Q68DV3
  9. NM_001415148.1NP_001402077.1  forkhead box protein O3 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL096818, AL365509, AL391646
    UniProtKB/TrEMBL
    A0A856PRE8, Q68DV3
  10. NM_001415149.1NP_001402078.1  forkhead box protein O3 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL096818, AL365509, AL391646
    UniProtKB/TrEMBL
    A0A856PRE8, Q68DV3
  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_2024_08

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

    UniProtKB/TrEMBL
    Q68DV3
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