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Aliases for FOXO3 Gene

Aliases for FOXO3 Gene

  • Forkhead Box O3 2 3 5
  • Forkhead In Rhabdomyosarcoma-Like 1 3 4
  • FKHRL1 3 4
  • FOXO3A 3 4
  • Forkhead, Drosophila, Homolog Of, In Rhabdomyosarcoma-Like 1 3
  • Forkhead Homolog (Rhabdomyosarcoma) Like 1 3
  • Forkhead Box Protein O3 3
  • Forkhead Box O3A 3
  • AF6q21 Protein 4
  • FKHRL1P2 3
  • AF6q21 3
  • FOXO2 3

External Ids for FOXO3 Gene

Previous HGNC Symbols for FOXO3 Gene

  • FKHRL1
  • FOXO3A

Previous GeneCards Identifiers for FOXO3 Gene

  • GC06P108988
  • GC06P108881
  • GC06P106448

Summaries for FOXO3 Gene

Entrez Gene Summary for FOXO3 Gene

  • 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]

GeneCards Summary for FOXO3 Gene

FOXO3 (Forkhead Box O3) is a Protein Coding gene. Diseases associated with FOXO3 include Chromosome 6Q Deletion and Rhabdomyosarcoma. Among its related pathways are Constitutive Signaling by AKT1 E17K in Cancer and NFAT and Cardiac Hypertrophy. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and protein kinase binding. An important paralog of this gene is FOXO1.

UniProtKB/Swiss-Prot for FOXO3 Gene

  • Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5-[AG]TAAA[TC]A-3. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3UTR of MYC transcript and prevent its translation.

Gene Wiki entry for FOXO3 Gene

Additional gene information for FOXO3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FOXO3 Gene

Genomics for FOXO3 Gene

GeneHancer (GH) Regulatory Elements for FOXO3 Gene

Promoters and enhancers for FOXO3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06I108555 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 565.2 +1.8 1839 11.9 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 ZNF143 ZNF548 SP3 NFYC FOXO3 PIR59886 ZBTB24 SMPD2 CD164 RNU6-653P ENSG00000271730 SEC63 LINC00222 SESN1
GH06I109453 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 9.8 +897.3 897337 7.8 HDGF PKNOX1 FOXA2 ARID4B ZBTB7B IRF4 ZNF143 SP3 REST SMARCA4 MICAL1 SMPD2 ZBTB24 METTL24 ENSG00000260273 LOC105377935 FOXO3 FIG4 PPIL6 CD164
GH06I108649 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 4.7 +93.8 93766 8.1 TFAP4 FOXA2 SAP130 CEBPG EBF1 RAD21 ZFHX2 POLR2A SCRT2 RCOR1 FOXO3 LINC00222 GC06P108702 GC06P108619
GH06I108620 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 5.3 +62.5 62461 3.1 CTCF ZNF449 ZIC2 FOSL1 ZNF335 CTBP1 PRDM6 ZSCAN5C FOS ZBTB33 FOXO3 GC06P108619 GC06P108702
GH06I108967 Enhancer 1.3 FANTOM5 Ensembl ENCODE 4.1 +408.1 408085 2.6 PKNOX1 BMI1 RFX5 ZNF335 GLIS2 EGR1 ZSCAN5C SCRT2 FOS EGR2 PIR34191 RNU6-653P ARMC2-AS1 ENSG00000271730 AK9 FOXO3 MICAL1 SMPD2 ARMC2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around FOXO3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the FOXO3 gene promoter:

Genomic Locations for FOXO3 Gene

Genomic Locations for FOXO3 Gene
chr6:108,559,823-108,684,774
(GRCh38/hg38)
Size:
124,952 bases
Orientation:
Plus strand
chr6:108,881,026-109,005,977
(GRCh37/hg19)

Genomic View for FOXO3 Gene

Genes around FOXO3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FOXO3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FOXO3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FOXO3 Gene

Proteins for FOXO3 Gene

  • Protein details for FOXO3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43524-FOXO3_HUMAN
    Recommended name:
    Forkhead box protein O3
    Protein Accession:
    O43524
    Secondary Accessions:
    • B4DVZ6
    • E1P5E6
    • O15171
    • Q5T2I7
    • Q9BZ04

    Protein attributes for FOXO3 Gene

    Size:
    673 amino acids
    Molecular mass:
    71277 Da
    Quaternary structure:
    • Interacts with SIRT2; the interaction occurs independently of SIRT2 deacetylase activity (By similarity). Interacts with YWHAB/14-3-3-beta and YWHAZ/14-3-3-zeta, which are required for cytosolic sequestration (PubMed:16751106). Upon oxidative stress, interacts with STK4/MST1, which disrupts interaction with YWHAB/14-3-3-beta and leads to nuclear translocation (PubMed:16751106). Interacts with PIM1 (PubMed:18593906). Interacts with DDIT3/CHOP (PubMed:22761832). Interacts (deacetylated form) with SKP2 (PubMed:21841822). Interacts with CHUK and IKBKB (PubMed:15084260, PubMed:22313691). Interacts with CAMK2A, CAMK2B and calcineurin A (By similarity).

    Three dimensional structures from OCA and Proteopedia for FOXO3 Gene

    Alternative splice isoforms for FOXO3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FOXO3 Gene

Post-translational modifications for FOXO3 Gene

  • Deacetylation by SIRT1 or SIRT2 stimulates interaction of FOXO3 with SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation (PubMed:21841822). Deacetylation by SIRT2 stimulates FOXO3-mediated transcriptional activity in response to oxidative stress (By similarity).
  • Heavily methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-271. Methylation doesnt affect subcellular location.
  • In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-253 by AKT1/PKB. This phosphorylated form then interacts with 14-3-3 proteins and is retained in the cytoplasm. Survival factor withdrawal induces dephosphorylation and promotes translocation to the nucleus where the dephosphorylated protein induces transcription of target genes and triggers apoptosis. Although AKT1/PKB doesnt appear to phosphorylate Ser-315 directly, it may activate other kinases that trigger phosphorylation at this residue. Phosphorylated by STK4/MST1 on Ser-209 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation. Phosphorylated by PIM1. Phosphorylation by AMPK leads to the activation of transcriptional activity without affecting subcellular localization. Phosphorylation by MAPKAPK5 promotes nuclear localization and DNA-binding, leading to induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3UTR of MYC transcript and prevent its translation (PubMed:10102273, PubMed:11154281, PubMed:16751106, PubMed:17711846, PubMed:18593906, PubMed:21329882). Phosphorylated by CHUK/IKKA and IKBKB/IKKB. TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-644 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:15084260). May be dephosphorylated by calcineurin A on Ser-299 which abolishes FOXO3 transcriptional activity (By similarity).
  • Polyubiquitinated. Ubiquitinated by a SCF complex containing SKP2, leading to proteasomal degradation.

No data available for DME Specific Peptides for FOXO3 Gene

Domains & Families for FOXO3 Gene

Gene Families for FOXO3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with FOXO3: view

No data available for UniProtKB/Swiss-Prot for FOXO3 Gene

Function for FOXO3 Gene

Molecular function for FOXO3 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5-[AG]TAAA[TC]A-3. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3UTR of MYC transcript and prevent its translation.

Phenotypes From GWAS Catalog for FOXO3 Gene

Gene Ontology (GO) - Molecular Function for FOXO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001047 core promoter binding ISS --
GO:0001221 transcription cofactor binding IEA --
GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding IDA 20371612
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding IEA --
GO:0003677 DNA binding IEA,IDA 21329882
genes like me logo Genes that share ontologies with FOXO3: view
genes like me logo Genes that share phenotypes with FOXO3: view

Animal Models for FOXO3 Gene

MGI Knock Outs for FOXO3:

Animal Model Products

miRNA for FOXO3 Gene

miRTarBase miRNAs that target FOXO3

Transcription Factor Targets for FOXO3 Gene

Selected GeneGlobe predicted Target genes for FOXO3
Targeted motifs for FOXO3 Gene
HOMER Transcription Factor Regulatory Elements motif FOXO3
  • Consensus sequence: DGTAAACA Submotif: canonical Cell Type: U2OS

Clone Products

  • Addgene plasmids for FOXO3

No data available for Enzyme Numbers (IUBMB) and Human Phenotype Ontology for FOXO3 Gene

Localization for FOXO3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FOXO3 Gene

Cytoplasm, cytosol. Nucleus. Note=Retention in the cytoplasm contributes to its inactivation. Translocates to the nucleus upon oxidative stress and in the absence of survival factors. {ECO:0000269 PubMed:10102273, ECO:0000269 PubMed:15084260, ECO:0000269 PubMed:16751106}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FOXO3 gene
Compartment Confidence
nucleus 5
cytosol 5
mitochondrion 4
plasma membrane 2
extracellular 2
lysosome 2
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for FOXO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IEA 10102273
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,IDA 10102273
GO:0005739 mitochondrion IEA --
GO:0005829 cytosol TAS,IDA --
genes like me logo Genes that share ontologies with FOXO3: view

Pathways & Interactions for FOXO3 Gene

genes like me logo Genes that share pathways with FOXO3: view

SIGNOR curated interactions for FOXO3 Gene

Gene Ontology (GO) - Biological Process for FOXO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 18787191
GO:0001542 ovulation from ovarian follicle IEA --
GO:0001544 initiation of primordial ovarian follicle growth IEA --
GO:0001547 antral ovarian follicle growth IEA --
GO:0001556 oocyte maturation IEA --
genes like me logo Genes that share ontologies with FOXO3: view

Drugs & Compounds for FOXO3 Gene

(14) Drugs for FOXO3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(6) Additional Compounds for FOXO3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with FOXO3: view

Transcripts for FOXO3 Gene

Unigene Clusters for FOXO3 Gene

Forkhead box O3:
Representative Sequences:

Clone Products

  • Addgene plasmids for FOXO3

Alternative Splicing Database (ASD) splice patterns (SP) for FOXO3 Gene

No ASD Table

Relevant External Links for FOXO3 Gene

GeneLoc Exon Structure for
FOXO3
ECgene alternative splicing isoforms for
FOXO3

Expression for FOXO3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for FOXO3 Gene

Protein differential expression in normal tissues from HIPED for FOXO3 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (27.6) and Cervix (21.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for FOXO3 Gene



NURSA nuclear receptor signaling pathways regulating expression of FOXO3 Gene:

FOXO3

SOURCE GeneReport for Unigene cluster for FOXO3 Gene:

Hs.220950

mRNA Expression by UniProt/SwissProt for FOXO3 Gene:

O43524-FOXO3_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for FOXO3 Gene

  • Muscle(4.6)
  • Nervous system(4.4)
  • Stomach(4.2)
  • Eye(3.4)
  • Heart(2.5)
  • Lung(2.5)
  • Bone marrow(2.4)
  • Blood(2.3)
  • Liver(2.2)
  • Adrenal gland(2)
  • Intestine(2)
  • Kidney(2)
genes like me logo Genes that share expression patterns with FOXO3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for FOXO3 Gene

Orthologs for FOXO3 Gene

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

Orthologs for FOXO3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FOXO3 33 34
  • 99.75 (n)
cow
(Bos Taurus)
Mammalia FOXO3 33 34
  • 91.17 (n)
dog
(Canis familiaris)
Mammalia FOXO3 33 34
  • 90.81 (n)
mouse
(Mus musculus)
Mammalia Foxo3 33 16 34
  • 89.68 (n)
rat
(Rattus norvegicus)
Mammalia Foxo3 33
  • 89.38 (n)
oppossum
(Monodelphis domestica)
Mammalia FOXO3 34
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia FOXO3 34
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves FOXO3 33 34
  • 79.24 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia foxo3 33
  • 70.79 (n)
Str.14701 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.2074 33
zebrafish
(Danio rerio)
Actinopterygii foxo3b 33 34
  • 62.34 (n)
foxo3a 34
  • 58 (a)
OneToMany
-- 33
fruit fly
(Drosophila melanogaster)
Insecta foxo 34
  • 32 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea daf-16 34
  • 28 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HCM1 34
  • 15 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3143 34
  • 25 (a)
OneToMany
Species where no ortholog for FOXO3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for FOXO3 Gene

ENSEMBL:
Gene Tree for FOXO3 (if available)
TreeFam:
Gene Tree for FOXO3 (if available)

Paralogs for FOXO3 Gene

Paralogs for FOXO3 Gene

(4) SIMAP similar genes for FOXO3 Gene using alignment to 2 proteins:

Pseudogenes.org Pseudogenes for FOXO3 Gene

genes like me logo Genes that share paralogs with FOXO3: view

Variants for FOXO3 Gene

Sequence variations from dbSNP and Humsavar for FOXO3 Gene

SNP ID Clin Chr 06 pos Variation AA Info Type
rs1000004149 -- 108,660,596(+) G/T intron_variant
rs1000006692 -- 108,616,153(+) A/G genic_upstream_transcript_variant, intron_variant
rs1000039915 -- 108,572,053(+) A/T genic_upstream_transcript_variant, intron_variant
rs1000077832 -- 108,560,322(+) C/T genic_upstream_transcript_variant, intron_variant, upstream_transcript_variant
rs1000087781 -- 108,603,216(+) G/A genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for FOXO3 Gene

Variant ID Type Subtype PubMed ID
dgv10904n54 CNV loss 21841781
esv22566 CNV loss 19812545
esv2651848 CNV deletion 19546169
nsv1017621 CNV gain 25217958
nsv1133101 OTHER inversion 24896259
nsv5433 CNV insertion 18451855
nsv604476 CNV gain 21841781
nsv604477 CNV gain 21841781
nsv604482 CNV gain 21841781
nsv823817 CNV gain 20364138
nsv830767 CNV gain 17160897
nsv950490 CNV duplication 24416366
nsv950491 CNV duplication 24416366
nsv981171 CNV duplication 23825009

Variation tolerance for FOXO3 Gene

Residual Variation Intolerance Score: 45.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.51; 55.40% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FOXO3 Gene

Human Gene Mutation Database (HGMD)
FOXO3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FOXO3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FOXO3 Gene

Disorders for FOXO3 Gene

MalaCards: The human disease database

(6) MalaCards diseases for FOXO3 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
chromosome 6q deletion
  • 6q deletion
rhabdomyosarcoma
cervix carcinoma
  • cancer of cervix
aging
suppurative cholangitis
- elite association - COSMIC cancer census association via MalaCards
Search FOXO3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FOXO3_HUMAN
  • Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with KMT2A/MLL1.

Additional Disease Information for FOXO3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with FOXO3: view

No data available for Genatlas for FOXO3 Gene

Publications for FOXO3 Gene

  1. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. (PMID: 9479491) Anderson MJ … Arden KC (Genomics 1998) 2 3 4 22 58
  2. Association of FOXO3A variation with human longevity confirmed in German centenarians. (PMID: 19196970) Flachsbart F … Nebel A (Proceedings of the National Academy of Sciences of the United States of America 2009) 3 22 44 58
  3. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. (PMID: 15084260) Hu MC … Hung MC (Cell 2004) 3 4 22 58
  4. Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). (PMID: 11154281) Brunet A … Greenberg ME (Molecular and cellular biology 2001) 3 4 22 58
  5. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. (PMID: 10102273) Brunet A … Greenberg ME (Cell 1999) 3 4 22 58

Products for FOXO3 Gene

  • Addgene plasmids for FOXO3

Sources for FOXO3 Gene

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