FOXO4 Gene (Protein Coding)

Forkhead Box O4

GC0XP071095
GIFtS:
43
This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located... See more...

Aliases for FOXO4 Gene

Aliases for FOXO4 Gene

  • Forkhead Box O4 2 3 5
  • AFX1 2 3 4
  • Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila); Translocated To, 7 2 3
  • Fork Head Domain Transcription Factor AFX1 3 4
  • Forkhead Box Protein O4 3 4
  • MLLT7 3 4
  • AFX 3 4
  • Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax (Drosophila) Homolog); Translocated To, 7 2
  • FOXO4 5

External Ids for FOXO4 Gene

Previous HGNC Symbols for FOXO4 Gene

  • MLLT7

Previous GeneCards Identifiers for FOXO4 Gene

  • GC0XP070233
  • GC0XP070316
  • GC0XP064135
  • GC0XP071096

Summaries for FOXO4 Gene

Entrez Gene Summary for FOXO4 Gene

  • This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

GeneCards Summary for FOXO4 Gene

FOXO4 (Forkhead Box O4) is a Protein Coding gene. Diseases associated with FOXO4 include Rhabdomyosarcoma 2. Among its related pathways are RET signaling and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and enzyme binding. An important paralog of this gene is FOXO1.

UniProtKB/Swiss-Prot Summary for FOXO4 Gene

  • Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity.

Gene Wiki entry for FOXO4 Gene

Additional gene information for FOXO4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FOXO4 Gene

Genomics for FOXO4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for FOXO4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FOXO4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FOXO4

Top Transcription factor binding sites by QIAGEN in the FOXO4 gene promoter:
  • c-Myb
  • E47
  • Evi-1
  • GR
  • GR-alpha
  • GR-beta
  • HFH-1
  • IRF-2
  • Tal-1

Genomic Locations for FOXO4 Gene

Latest Assembly
chrX:71,095,851-71,103,534
(GRCh38/hg38)
Size:
7,684 bases
Orientation:
Plus strand

Previous Assembly
chrX:70,315,701-70,323,382
(GRCh37/hg19 by Entrez Gene)
Size:
7,682 bases
Orientation:
Plus strand

chrX:70,316,047-70,323,385
(GRCh37/hg19 by Ensembl)
Size:
7,339 bases
Orientation:
Plus strand

Genomic View for FOXO4 Gene

Genes around FOXO4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FOXO4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FOXO4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for FOXO4 Gene

Proteins for FOXO4 Gene

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  3. Assay products for research

  • Protein details for FOXO4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P98177-FOXO4_HUMAN
    Recommended name:
    Forkhead box protein O4
    Protein Accession:
    P98177
    Secondary Accessions:
    • B7WPJ7
    • O43821
    • Q13720
    • Q3KPF1
    • Q8TDK9

    Protein attributes for FOXO4 Gene

    Size:
    505 amino acids
    Molecular mass:
    53684 Da
    Quaternary structure:
    • Interacts with CREBBP/CBP, CTNNB1, MYOCD, SIRT1, SRF and YWHAZ. Acetylated by CREBBP/CBP and deacetylated by SIRT1. Binding of YWHAZ inhibits DNA-binding. Interacts with USP7; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of TP53. Interacts with NLK, and this inhibits monoubiquitination and transcriptional activity. Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (By similarity).

    Three dimensional structures from OCA and Proteopedia for FOXO4 Gene

    Alternative splice isoforms for FOXO4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FOXO4 Gene

Protein Expression for FOXO4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for FOXO4 Gene

  • Acetylation by CREBBP/CBP, which is induced by peroxidase stress, inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity.
  • Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK.
  • Monoubiquitinated; monoubiquitination is induced by oxidative stress and reduced by deacetylase inhibitors; results in its relocalization to the nucleus and its increased transcriptional activity. Deubiquitinated by USP7; deubiquitination is induced by oxidative stress; enhances its interaction with USP7 and consequently, deubiquitination; increases its translocation to the cytoplasm and inhibits its transcriptional activity. Hydrogene-peroxide-induced ubiquitination and USP7-mediated deubiquitination have no major effect on its protein stability.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for FOXO4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

No data available for DME Specific Peptides for FOXO4 Gene

Domains & Families for FOXO4 Gene

Gene Families for FOXO4 Gene

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

Protein Domains for FOXO4 Gene

InterPro:

Suggested Antigen Peptide Sequences for FOXO4 Gene

GenScript: Design optimal peptide antigens:
  • Fork head domain transcription factor AFX1 (FOXO4_HUMAN)
genes like me logo Genes that share domains with FOXO4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for FOXO4 Gene

Function for FOXO4 Gene

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  6. Cell Lines for research

Molecular function for FOXO4 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity.

Gene Ontology (GO) - Molecular Function for FOXO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 11689711
GO:0003677 DNA binding IEA,IDA 10783894
GO:0003700 DNA-binding transcription factor activity IDA 10783894
genes like me logo Genes that share ontologies with FOXO4: view
genes like me logo Genes that share phenotypes with FOXO4: view

Animal Models for FOXO4 Gene

MGI Knock Outs for FOXO4:

Animal Models for research

  • Taconic Biosciences Mouse Models for FOXO4

Transcription Factor Targets for FOXO4 Gene

Selected GeneGlobe predicted Target genes for FOXO4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FOXO4

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Human Phenotype Ontology and HOMER Transcription for FOXO4 Gene

Localization for FOXO4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FOXO4 Gene

Cytoplasm. Nucleus. Note=When phosphorylated, translocated from nucleus to cytoplasm. Dephosphorylation triggers nuclear translocation. Monoubiquitination increases nuclear localization. When deubiquitinated, translocated from nucleus to cytoplasm.

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 FOXO4 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nuclear speckles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FOXO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IBA,TAS 22972301
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,IDA 16964248
GO:0005829 cytosol TAS 22972301
genes like me logo Genes that share ontologies with FOXO4: view

Pathways & Interactions for FOXO4 Gene

genes like me logo Genes that share pathways with FOXO4: view

SIGNOR curated interactions for FOXO4 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for FOXO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IDA 15126506
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007049 cell cycle IEA --
GO:0007050 cell cycle arrest IDA 10783894
GO:0007095 mitotic G2 DNA damage checkpoint IEA --
genes like me logo Genes that share ontologies with FOXO4: view

Drugs & Compounds for FOXO4 Gene

Products:

  1. Drug products for research

(2) Drugs for FOXO4 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NAD Experimental Pharma 0

(2) Additional Compounds for FOXO4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with FOXO4: view

Transcripts for FOXO4 Gene

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mRNA/cDNA for FOXO4 Gene

2 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FOXO4

Alternative Splicing Database (ASD) splice patterns (SP) for FOXO4 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5
SP1: -
SP2: -
SP3:

Relevant External Links for FOXO4 Gene

GeneLoc Exon Structure for
FOXO4

Expression for FOXO4 Gene

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  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FOXO4 Gene

mRNA expression in normal human tissues for FOXO4 Gene
mRNA expression by GTEx for FOXO4 GenemRNA expression by BioGPS for FOXO4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for FOXO4 Gene

This gene is overexpressed in Fetal ovary (51.3), Placenta (8.9), and Fetal testis (8.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for FOXO4 Gene



Protein tissue co-expression partners for FOXO4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FOXO4

SOURCE GeneReport for Unigene cluster for FOXO4 Gene:

Hs.584654

mRNA Expression by UniProt/SwissProt for FOXO4 Gene:

P98177-FOXO4_HUMAN
Tissue specificity: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform zeta is most abundant in the liver, kidney, and pancreas.

Evidence on tissue expression from TISSUES for FOXO4 Gene

  • Blood(4.5)
  • Bone marrow(4.5)
  • Muscle(2.9)
  • Nervous system(2.7)
  • Heart(2.6)
  • Liver(2.5)
  • Intestine(2.4)
  • Kidney(2.4)
  • Spleen(2.2)
  • Skin(2.2)
  • Lung(2.1)
  • Pancreas(2.1)
  • Adrenal gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FOXO4 Gene

Germ Layers:
  • mesoderm
Systems:
  • cardiovascular
Regions:
General:
  • blood
  • bone marrow
  • white blood cell
genes like me logo Genes that share expression patterns with FOXO4: view

Primer products for research

No data available for mRNA differential expression in normal tissues for FOXO4 Gene

Orthologs for FOXO4 Gene

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

Orthologs for FOXO4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia FOXO4 29 30
  • 97.77 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia FOXO4 29 30
  • 91.02 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia FOXO4 29 30
  • 90.5 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Foxo4 29 16 30
  • 88.36 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Foxo4 29
  • 88.36 (n)
Oppossum
(Monodelphis domestica)
 Mammalia FOXO4 30
  • 83 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves FOXO4 29 30
  • 60.19 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia FOXO4 30
  • 53 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia LOC100492831 29
  • 58.43 (n)
Zebrafish
(Danio rerio)
 Actinopterygii LOC563719 29
  • 58.46 (n)
FOXO4 30
  • 37 (a)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta foxo 30
  • 26 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea daf-16 30
  • 24 (a)
 OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes HCM1 30
  • 12 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea CSA.3143 30
  • 21 (a)
 OneToMany
Species where no ortholog for FOXO4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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 FOXO4 Gene

ENSEMBL:
Gene Tree for FOXO4 (if available)
TreeFam:
Gene Tree for FOXO4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FOXO4: view image
Alliance of Genome Resources:
Additional Orthologs for FOXO4

Paralogs for FOXO4 Gene

Paralogs for FOXO4 Gene

(4) SIMAP similar genes for FOXO4 Gene using alignment to 1 proteins:

  • FOXO4_HUMAN
genes like me logo Genes that share paralogs with FOXO4: view

Variants for FOXO4 Gene

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  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FOXO4 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
993788 Uncertain Significance: none provided 71,096,913(+) G/T
NM_005938.4(FOXO4):c.385G>T (p.Glu129Ter) 		NONSENSE
rs142962975 Benign: not provided 71,100,917(+) G/A
NM_005938.4(FOXO4):c.687G>A (p.Thr229=) 		SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for FOXO4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for FOXO4 Gene

Variant ID Type Subtype PubMed ID
esv1584074 OTHER inversion 17803354
esv33082 CNV loss 17666407

Variation tolerance for FOXO4 Gene

Residual Variation Intolerance Score: 43% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.53; 11.45% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FOXO4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
FOXO4
Leiden Open Variation Database (LOVD)
FOXO4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FOXO4 Gene

Disorders for FOXO4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for FOXO4 Gene - From: COP

Disorder Aliases PubMed IDs
rhabdomyosarcoma 2
  • rms2
- elite association - COSMIC cancer census association via MalaCards
Search FOXO4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FOXO4_HUMAN
  • Note=A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23) with KMT2A/MLL1. The result is a rogue activator protein.

Additional Disease Information for FOXO4

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with FOXO4: view

No data available for Genatlas for FOXO4 Gene

Publications for FOXO4 Gene

  1. Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. (PMID: 15688030) Yang H … Lee MH (Oncogene 2005) 3 4 22
  2. Regulation of intracellular localization and transcriptional activity of FOXO4 by protein kinase B through phosphorylation at the motif sites conserved among the FOXO family. (PMID: 16272144) Matsuzaki H … Kikkawa U (Journal of biochemistry 2005) 3 4 22
  3. Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin. (PMID: 16054032) Liu ZP … Olson EN (Developmental cell 2005) 3 4 22
  4. Solution structure of the DNA binding domain of the human forkhead transcription factor AFX (FOXO4). (PMID: 11352721) Weigelt J … Wikström M (Biochemistry 2001) 3 4 22
  5. Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. (PMID: 10518537) Takaishi H … Nishizuka Y (Proceedings of the National Academy of Sciences of the United States of America 1999) 3 4 22

ExternalLinks

View latest publications for FOXO4 gene in Mastermind

Products for FOXO4 Gene

  • Addgene plasmids for FOXO4

Sources for FOXO4 Gene