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Aliases for FOXO4 Gene

Aliases for FOXO4 Gene

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

External Ids for FOXO4 Gene

Previous HGNC Symbols for FOXO4 Gene

  • MLLT7

Previous GeneCards Identifiers for FOXO4 Gene

  • GC0XP070233
  • GC0XP070316
  • GC0XP064135

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 myeloid/lymphoid or mixed lineage leukemia and sarcomatoid squamous cell skin carcinoma. Among its related pathways are Signaling by GPCR and Immune System. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and enzyme binding. An important paralog of this gene is FOXO6.

UniProtKB/Swiss-Prot 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FOXO4 Gene

Genomics for FOXO4 Gene

Regulatory Elements for FOXO4 Gene

Promoters for FOXO4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around FOXO4 on UCSC Golden Path with GeneCards custom track

Genomic Location for FOXO4 Gene

Chromosome:
X
Start:
71,096,149 bp from pter
End:
71,103,535 bp from pter
Size:
7,387 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 StructureGene Density

RefSeq DNA sequence for FOXO4 Gene

Proteins for FOXO4 Gene

  • 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.

    Three dimensional structures from OCA and Proteopedia for FOXO4 Gene

    Alternative splice isoforms for FOXO4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FOXO4 Gene

Proteomics data for FOXO4 Gene at MOPED

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.
  • 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.
  • Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for FOXO4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for FOXO4 Gene

Domains & Families for FOXO4 Gene

Gene Families for FOXO4 Gene

Protein Domains for FOXO4 Gene

Suggested Antigen Peptide Sequences for FOXO4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P98177

UniProtKB/Swiss-Prot:

FOXO4_HUMAN :
  • Contains 1 fork-head DNA-binding domain.
Domain:
  • Contains 1 fork-head DNA-binding domain.
genes like me logo Genes that share domains with FOXO4: view

Function for FOXO4 Gene

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:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding IBA --
GO:0008013 beta-catenin binding IDA 15905404
GO:0008134 transcription factor binding IPI 16054032
GO:0042802 identical protein binding IPI 25609649
genes like me logo Genes that share ontologies with FOXO4: view
genes like me logo Genes that share phenotypes with FOXO4: view

Human Phenotype Ontology for FOXO4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for FOXO4 Gene

MGI Knock Outs for FOXO4:

Animal Model Products

CRISPR Products

miRNA for FOXO4 Gene

Transcription Factor Targets for FOXO4 Gene

Selected GeneGlobe predicted Target genes for FOXO4

No data available for Enzyme Numbers (IUBMB) 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
Jensen Localization Image for FOXO4 Gene COMPARTMENTS Subcellular localization image for FOXO4 gene
Compartment Confidence
cytosol 5
nucleus 5
cytoskeleton 2
lysosome 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for FOXO4 Gene

Pathways & Interactions for FOXO4 Gene

SuperPathways for FOXO4 Gene

Superpath Contained pathways
1 Interleukin-3, 5 and GM-CSF signaling
2 PI3K events in ERBB4 signaling
3 IL-7 Signaling Pathways
4 Immune System
5 Downstream signaling events of B Cell Receptor (BCR)
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 IEA,IDA 15126506
GO:0006366 transcription from RNA polymerase II promoter TAS 10783894
GO:0007095 mitotic G2 DNA damage checkpoint IEA --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0008286 insulin receptor signaling pathway IDA 10217147
genes like me logo Genes that share ontologies with FOXO4: view

Drugs & Compounds for FOXO4 Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NAD Pharma Full agonist, Agonist 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

Unigene Clusters for FOXO4 Gene

Forkhead box O4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Flow Cytometry Products

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
ECgene alternative splicing isoforms for
FOXO4

Expression for FOXO4 Gene

mRNA expression in normal human tissues 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, PaxDb, and MOPED for FOXO4 Gene



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.
genes like me logo Genes that share expression patterns with FOXO4: view

Protein tissue co-expression partners for FOXO4 Gene

Primer Products

In Situ Assay Products

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 36
  • 100 (a)
OneToOne
FOXO4 35
  • 97.77 (n)
  • 97.16 (a)
mouse
(Mus musculus)
Mammalia Foxo4 36
  • 89 (a)
OneToOne
Foxo4 16
Foxo4 35
  • 88.36 (n)
  • 88.69 (a)
oppossum
(Monodelphis domestica)
Mammalia FOXO4 36
  • 83 (a)
OneToOne
dog
(Canis familiaris)
Mammalia FOXO4 36
  • 92 (a)
OneToOne
FOXO4 35
  • 91.02 (n)
  • 92.08 (a)
cow
(Bos Taurus)
Mammalia FOXO4 36
  • 88 (a)
OneToOne
FOXO4 35
  • 90.5 (n)
  • 89.11 (a)
rat
(Rattus norvegicus)
Mammalia Foxo4 35
  • 88.36 (n)
  • 88.49 (a)
chicken
(Gallus gallus)
Aves FOXO4 36
  • 48 (a)
OneToOne
FOXO4 35
  • 60.19 (n)
  • 59.72 (a)
lizard
(Anolis carolinensis)
Reptilia FOXO4 36
  • 53 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100492831 35
  • 58.43 (n)
  • 59.82 (a)
zebrafish
(Danio rerio)
Actinopterygii FOXO4 36
  • 37 (a)
OneToOne
LOC563719 35
  • 58.46 (n)
  • 57.11 (a)
fruit fly
(Drosophila melanogaster)
Insecta foxo 36
  • 26 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea daf-16 36
  • 24 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HCM1 36
  • 12 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3143 36
  • 21 (a)
OneToMany
Species with no ortholog for FOXO4:
  • A. gosspyii yeast (Ashbya 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 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)

Paralogs for FOXO4 Gene

Paralogs for FOXO4 Gene

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

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

Variants for FOXO4 Gene

Sequence variations from dbSNP and Humsavar for FOXO4 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
rs1142823 -- 71,101,495(+) GGCTC(C/G)AGGCC reference, missense
rs4259556 -- 71,100,249(+) GGGCA(C/T)CCCCC intron-variant
rs4503258 -- 71,103,387(+) CTTTG(C/T)ATCGT utr-variant-3-prime
rs4489469 -- 71,100,139(+) AGGAG(A/C)ACGTC intron-variant
rs5936624 -- 71,094,283(+) AGAAA(A/G)AGAAA upstream-variant-2KB

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)

Relevant External Links for FOXO4 Gene

HapMap Linkage Disequilibrium report
FOXO4

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

Disorders for FOXO4 Gene

MalaCards: The human disease database

(5) MalaCards diseases for FOXO4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
myeloid/lymphoid or mixed lineage leukemia
  • mll
sarcomatoid squamous cell skin carcinoma
  • spindle cell squamous cell carcinoma
cutaneous leiomyosarcoma
  • leiomyosarcoma of the skin
connective tissue cancer
  • connective tissue neoplasm
branch retinal artery occlusion
  • arterial retinal branch occlusion
- 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.

Relevant External Links for FOXO4

Genetic Association Database (GAD)
FOXO4
Human Genome Epidemiology (HuGE) Navigator
FOXO4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
FOXO4
genes like me logo Genes that share disorders with FOXO4: view

No data available for Genatlas for FOXO4 Gene

Publications for FOXO4 Gene

  1. Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. (PMID: 7529552) Parry P. … Evans G. (Genes Chromosomes Cancer 1994) 2 3 4 67
  2. The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors. (PMID: 19244250) Essaghir A. … Demoulin J.B. (J. Biol. Chem. 2009) 3 23
  3. FoxO4 inhibits NF-kappaB and protects mice against colonic injury and inflammation. (PMID: 19560465) Zhou W. … Liu Z.P. (Gastroenterology 2009) 3 23
  4. Splice variants of the forkhead box protein AFX exhibit dominant negative activity and inhibit AFXalpha-mediated tumor cell apoptosis. (PMID: 18648506) Lee E.J. … Jameson J.L. (PLoS ONE 2008) 3 23
  5. Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. (PMID: 15688030) Yang H. … Lee M.-H. (Oncogene 2005) 3 23

Products for FOXO4 Gene

Sources for FOXO4 Gene

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