GenAge entry for FOXO3 (Homo sapiens)

Gene name (HAGRID: 123)

HGNC symbol
FOXO3 
Aliases
AF6q21; FOXO2; FKHRL1; FOXO3A 
Common name
forkhead box O3 

Potential relevance to the human ageing process

Main reason for selection
Entry selected based on evidence linking the gene or its product to human longevity and/or multiple age-related phenotypes
Description

A transcription factor of the Fox family, FOXO3, is crucial in development [802]. It also appears to regulate apoptotic signals in conjunction with FAS and AKT1.

A homologue of FOXO3, daf-16, has been associated with ageing in roundworms [628], and overexpression of another homologue, dFOXO, in adult fat body of fruit flies increased longevity in females [1238]. Female mice without FOXO3 showed an ovarian phenotype of follicular activation leading to oocyte death, early depletion of functional ovarian follicles, and secondary infertility [625].

Two studies of genetic variation within FOXO3, have found it to be associated with exceptional human longevity, among people of Japanese [1987] and German [1983] origin. The G allele of FOXO3 single nucleotide polymorphism (SNP) rs2802292 has been associated with longevity in multiple populations. G-allele carriers among combined Japanese, white and black populations have a risk reduction of 10% for total mortality [4357].

Cytogenetic information

Cytogenetic band
6q21
Location
108,560,866 bp to 108,684,768 bp
Orientation
Plus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0000122; negative regulation of transcription from RNA polymerase II promoter
GO:0001542; ovulation from ovarian follicle
GO:0001544; initiation of primordial ovarian follicle growth
GO:0001547; antral ovarian follicle growth
GO:0001556; oocyte maturation
GO:0006357; regulation of transcription from RNA polymerase II promoter
GO:0006366; transcription from RNA polymerase II promoter
GO:0006417; regulation of translation
GO:0007568; aging
GO:0030330; DNA damage response, signal transduction by p53 class mediator
GO:0031667; response to nutrient levels
GO:0033209; tumor necrosis factor-mediated signaling pathway
GO:0034599; cellular response to oxidative stress
GO:0042493; response to drug
GO:0043065; positive regulation of apoptotic process
GO:0043525; positive regulation of neuron apoptotic process
GO:0045648; positive regulation of erythrocyte differentiation
GO:0045665; negative regulation of neuron differentiation
GO:0045893; positive regulation of transcription, DNA-templated
GO:0045944; positive regulation of transcription from RNA polymerase II promoter
GO:0048854; brain morphogenesis
GO:0071333; cellular response to glucose stimulus
GO:0071386; cellular response to corticosterone stimulus
GO:0071456; cellular response to hypoxia
GO:0071548; response to dexamethasone
GO:0090090; negative regulation of canonical Wnt signaling pathway
GO:0097150; neuronal stem cell population maintenance
GO:0097192; extrinsic apoptotic signaling pathway in absence of ligand
GO:1901300; positive regulation of hydrogen peroxide-mediated programmed cell death
GO:1903428; positive regulation of reactive oxygen species biosynthetic process
GO:1904646; cellular response to beta-amyloid
GO:1990090; cellular response to nerve growth factor stimulus
GO:1990785; response to water-immersion restraint stress
GO:2000177; regulation of neural precursor cell proliferation
GO:2000353; positive regulation of endothelial cell apoptotic process
Cellular component: GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005737; cytoplasm
GO:0005739; mitochondrion
GO:0005829; cytosol
GO:0016020; membrane
Function: GO:0001047; core promoter binding
GO:0001221; transcription cofactor binding
GO:0001227; transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0001228; transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003677; DNA binding
GO:0003700; transcription factor activity, sequence-specific DNA binding
GO:0005515; protein binding
GO:0008013; beta-catenin binding
GO:0019901; protein kinase binding
GO:0031490; chromatin DNA binding
GO:0043565; sequence-specific DNA binding
Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
TP53, TERT, ATM, AKT1, MYC, BRCA1, CREBBP, EP300, PCNA, RB1, SIRT1, YWHAZ, MDM2, H2AFX, CTNNB1, SIRT3, IKBKB
STRING interaction network
Protein-Protein network diagram for FOXO3

Retrieve sequences for FOXO3

ORF
ORF
CDS
CDS

Homologs in model organisms

Danio rerio
foxo3a
Mus musculus
Foxo3
Rattus norvegicus
Foxo3

In other databases

GenDR gene manipulations
  • A homolog of this gene for Mus musculus is present as Foxo3
LongevityMap
  • This gene is present as FOXO3
CellAge
  • This gene is present as FOXO3

Selected references

External links

EPD
ORF Accession
NM_001455
CDS Accession
NP_001446
OMIM
602681
HPRD
04061
Ensembl
FOXO3
UniProt/Swiss-Prot
FOXO3_HUMAN
GeneCards
FOXO3
Entrez Gene
2309
UniGene
220950
GenAtlas
FOXO3
Internet
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