FOXO3 forkhead box O3 [Homo sapiens (human)] - Gene

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: mouse all
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Genomic context

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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer.
Title: The role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer.
Genetic Profile of FOXO3 Single-Nucleotide Polymorphism in Colorectal Cancer Patients.
Title: Genetic Profile of FOXO3 Single-Nucleotide Polymorphism in Colorectal Cancer Patients.
Helicobacter pylori CagA protein induces gastric cancer stem cell-like properties through the Akt/FOXO3a axis.
Title: Helicobacter pylori CagA protein induces gastric cancer stem cell-like properties through the Akt/FOXO3a axis.
CircFOXO3 mediates hypoxia-induced autophagy of endometrial stromal cells in endometriosis.
Title: CircFOXO3 mediates hypoxia-induced autophagy of endometrial stromal cells in endometriosis.
FOXO3a-interacting proteins' involvement in cancer: a review.
Title: FOXO3a-interacting proteins' involvement in cancer: a review.
FOXO3a functions as a transcriptional and co-transcriptional splicing regulator in vascular endothelial cell lines.
Title: FOXO3a functions as a transcriptional and co-transcriptional splicing regulator in vascular endothelial cell lines.
FOXO3 longevity genotype attenuates the impact of hypertension on cerebral microinfarct risk.
Title: FOXO3 longevity genotype attenuates the impact of hypertension on cerebral microinfarct risk.
The Role of microRNA-23a-3p in the Progression of Human Aging Process by Targeting FOXO3a.
Title: The Role of microRNA-23a-3p in the Progression of Human Aging Process by Targeting FOXO3a.
ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis.
Title: ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis.
FOXO3a-regulated arginine metabolic plasticity adaptively promotes esophageal cancer proliferation and metastasis.
Title: FOXO3a-regulated arginine metabolic plasticity adaptively promotes esophageal cancer proliferation and metastasis.

Submit: New GeneRIF Correction See all GeneRIFs (705)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A008N03 (e-PCR)
- UniSTS:42785

D11S2560 (e-PCR)
- UniSTS:37928

RH75343 (e-PCR)
- UniSTS:85845

SHGC-36190 (e-PCR)
- UniSTS:59989

FOXO3A_4088 (e-PCR)
- UniSTS:464480

MARC_14315-14316:1007670343:1 (e-PCR)
- UniSTS:267641

RH78823 (e-PCR)
- UniSTS:89240

SGC33792 (e-PCR)
- UniSTS:78746

Foxo3 (e-PCR), detects polymorphism
- UniSTS:547229

D17S1454E (e-PCR)
- UniSTS:150494

RH65484 (e-PCR)
- UniSTS:54240

D6S2431 (e-PCR), detects polymorphism
- UniSTS:3814

RH79704 (e-PCR)
- UniSTS:91367

RH69580 (e-PCR)
- UniSTS:83688

RH67795 (e-PCR)
- UniSTS:92406

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

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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)

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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)

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

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646
NM_001415140.1 → NP_001402069.1 forkhead box protein O3 isoform 3

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646
NM_001415141.1 → NP_001402070.1 forkhead box protein O3 isoform 3

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646
NM_001415142.1 → NP_001402071.1 forkhead box protein O3 isoform 3

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646
NM_001415144.1 → NP_001402073.1 forkhead box protein O3 isoform 4

Status: REVIEWED

Source sequence(s)

AL096818, AL365509

UniProtKB/TrEMBL

A0A856PRE8
NM_001415145.1 → NP_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
NM_001415146.1 → NP_001402075.1 forkhead box protein O3 isoform 4

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646

UniProtKB/TrEMBL

A0A856PRE8
NM_001415147.1 → NP_001402076.1 forkhead box protein O3 isoform 4

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646

UniProtKB/TrEMBL

A0A856PRE8
NM_001415148.1 → NP_001402077.1 forkhead box protein O3 isoform 4

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646

UniProtKB/TrEMBL

A0A856PRE8
NM_001415149.1 → NP_001402078.1 forkhead box protein O3 isoform 4

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646

UniProtKB/TrEMBL

A0A856PRE8
NM_001415150.1 → NP_001402079.1 forkhead box protein O3 isoform 5

Status: REVIEWED

Source sequence(s)

AL096818, AL365509, AL391646
NM_001455.4 → NP_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:157 → 237

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:433 → 508

FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2

pfam16676
Location:606 → 644

FOXO-TAD; Transactivation domain of FOXO protein family
NM_201559.3 → NP_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:157 → 237

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:433 → 508

FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2

pfam16676
Location:606 → 644

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

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

108559825..108684774

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

Q68DV3

Conserved Domains (3) summary

pfam16675
Location:244 → 319

FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2

pfam16676
Location:417 → 455

FOXO-TAD; Transactivation domain of FOXO protein family

cl00061
Location:17 → 50

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 ...
XM_017010586.2 → XP_016866075.1 forkhead box protein O3 isoform X2

UniProtKB/TrEMBL

A0A856PRE8, Q68DV3

Conserved Domains (3) summary

pfam16675
Location:213 → 287

FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2

pfam16676
Location:386 → 424

FOXO-TAD; Transactivation domain of FOXO protein family

cl00061
Location:1 → 25

FH_FOX; Forkhead (FH) domain found in Forkhead box (FOX) family of transcription factors and similar proteins