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FOXO4 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7)

Written1998-04Olivier Bernard
Unite Inserm U434, CNRS, Institut de Genetique Moleculaire, Paris, France
Updated2001-08Stig E. Bojesen
Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark

(Note : for Links provided by Atlas : click)

Identity

Other namesAFX1 (ALL1 fused gene from chromosome X, 1)
MLLT7 (myeloid/lymphoid leukemia translocated to, 7)
AFX
FOXO4
HGNC (Hugo) FOXO4
LocusID (NCBI) 4303
Atlas_Id 57
Location Xq13.1  [Link to chromosome band Xq13]
Location_base_pair Starts at 70315999 and ends at 70323384 bp from pter ( according to hg19-Feb_2009)  [Mapping FOXO4.png]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
CIC (19q13.2) / FOXO4 (Xq13.1)FOXO4 (Xq13.1) / FOXO4 (Xq13.1)FOXO4 (Xq13.1) / KMT2A (11q23.3)
FOXO4 (Xq13.1) / VAV3 (1p13.3)KMT2A (11q23.3) / FOXO4 (Xq13.1)PAX3 (2q36.1) / FOXO4 (Xq13.1)

DNA/RNA

Transcription 7,5kb consisting of 3 exons. RNA App. 3.5 kb mRNA; coding sequence. Placental secondary transcript: App. 2.8kb Expression pattern: Heavily expressed in skeletal muscle, placenta and ovary

Protein

Description 504 amino acids; NH2 -- similarity region with AF6q21 and FHKR -- forkhead motif -- COOH
Expression wide
Localisation nuclear
Function Transcription factor binding to the motive TTGTTTAC. Target genes: Akt, AFX is able to induce Rb-independent, p27kip1-mediated G1-arrest. Phosphorylation of AFX by protein kinase B inhibits its transcriptional activity.
Homology daf-16 (C.elegans) and other forkhead-transcription factors (i.e. FKHR, FKHRL1, FKHRP1, FKHRL1P1) and AF6q21, involved in the t(6;11)(q21;q23). In the fusion protein AFX/MLL, AFX fuses to MLL in the same aminoacid as FHKR fuses to PAX3 in the PAX3/FKHR-fusion protein of alveolar rabdomyosarcoma.

Implicated in

Note
Entity t(X;11)(q13q23)/acute leukaemias --> MLL - AFX
Disease AML, T-ALL
Prognosis very poor
Hybrid/Mutated Gene 5' MLL-3' AFX as well as the reciprocal 5' AFX-3' MLL on DNA and mRNA level
Abnormal Protein comprises about 1400 amino acids from N-term MLL and 354 amino acids from AFX C-term; the reciprocal may be expressed
  

Breakpoints

 

Bibliography

Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23).
Borkhardt A, Repp R, Haas OA, Leis T, Harbott J, Kreuder J, Hammermann J, Henn T, Lampert F
Oncogene. 1997 ; 14 (2) : 195-202.
PMID 9010221
 
Direct control of the Forkhead transcription factor AFX by protein kinase B.
Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM
Nature. 1999 ; 398 (6728) : 630-634.
PMID 10217147
 
AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.
Medema RH, Kops GJ, Bos JL, Burgering BM
Nature. 2000 ; 404 (6779) : 782-787.
PMID 10783894
 
Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.
Parry P, Wei Y, Evans G
Genes, chromosomes & cancer. 1994 ; 11 (2) : 79-84.
PMID 7529552
 
AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism.
Peters U, Haberhausen G, Kostrzewa M, Nolte D, Müller U
Human genetics. 1997 ; 100 (5-6) : 569-572.
PMID 9341872
 

Citation

This paper should be referenced as such :
Bojesen, SE
MLLT7 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):247-248.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/AFX1ID57.html
History of this paper:
Bernard, O. AFX1 (ALL1 fused gene from chromosome X, 1). Atlas Genet Cytogenet Oncol Haematol. 1998;2(3):74-74.
http://documents.irevues.inist.fr/bitstream/handle/2042/37428/04-1998-AFX1ID57.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  11q23 rearrangements (KMT2A) in leukaemia
t(X;11)(q13;q23) KMT2A/FOXO4
t(X;11)(q22;q23) KMT2A/?

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ]
  Soft Tissues: Alveolar rhabdomyosarcoma
Soft Tissues: Rhabdomyosarcoma
Soft tissue tumors: an overview
Soft Tissues: Alveolar rhabdomyosarcoma with t(2;13)(q35;q14) PAX3/FOXO1

External links

Nomenclature
HGNC (Hugo)FOXO4   7139
Cards
AtlasAFX1ID57
Entrez_Gene (NCBI)FOXO4  4303  forkhead box O4
AliasesAFX; AFX1; MLLT7
GeneCards (Weizmann)FOXO4
Ensembl hg19 (Hinxton)ENSG00000184481 [Gene_View]  chrX:70315999-70323384 [Contig_View]  FOXO4 [Vega]
Ensembl hg38 (Hinxton)ENSG00000184481 [Gene_View]  chrX:70315999-70323384 [Contig_View]  FOXO4 [Vega]
ICGC DataPortalENSG00000184481
TCGA cBioPortalFOXO4
AceView (NCBI)FOXO4
Genatlas (Paris)FOXO4
WikiGenes4303
SOURCE (Princeton)FOXO4
Genomic and cartography
GoldenPath hg19 (UCSC)FOXO4  -     chrX:70315999-70323384 +  Xq13.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)FOXO4  -     Xq13.1   [Description]    (hg38-Dec_2013)
EnsemblFOXO4 - Xq13.1 [CytoView hg19]  FOXO4 - Xq13.1 [CytoView hg38]
Mapping of homologs : NCBIFOXO4 [Mapview hg19]  FOXO4 [Mapview hg38]
OMIM300033   
Gene and transcription
Genbank (Entrez)AF384029 AK300142 AW292413 BC026735 BC106761
RefSeq transcript (Entrez)NM_001170931 NM_005938
RefSeq genomic (Entrez)NC_000023 NC_018934 NG_016418 NT_011651 NW_004929443
Consensus coding sequences : CCDS (NCBI)FOXO4
Cluster EST : UnigeneHs.584654 [ NCBI ]
CGAP (NCI)Hs.584654
Alternative Splicing GalleryENSG00000184481
Gene ExpressionFOXO4 [ NCBI-GEO ]   FOXO4 [ EBI - ARRAY_EXPRESS ]   FOXO4 [ SEEK ]   FOXO4 [ MEM ]
Gene Expression Viewer (FireBrowse)FOXO4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4303
GTEX Portal (Tissue expression)FOXO4
Protein : pattern, domain, 3D structure
UniProt/SwissProtP98177 (Uniprot)
NextProtP98177  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP98177
Splice isoforms : SwissVarP98177 (Swissvar)
PhosPhoSitePlusP98177
Domaine pattern : Prosite (Expaxy)FORK_HEAD_2 (PS00658)    FORK_HEAD_3 (PS50039)   
Domains : Interpro (EBI)Fork_head_dom    FOXO-TAD    TF_fork_head_CS_2    WHTH_DNA-bd_dom   
Domain families : Pfam (Sanger)Forkhead (PF00250)    FOXO-TAD (PF16676)   
Domain families : Pfam (NCBI)pfam00250    pfam16676   
Domain families : Smart (EMBL)FH (SM00339)  
DMDM Disease mutations4303
Blocks (Seattle)FOXO4
PDB (SRS)1E17    3L2C   
PDB (PDBSum)1E17    3L2C   
PDB (IMB)1E17    3L2C   
PDB (RSDB)1E17    3L2C   
Structural Biology KnowledgeBase1E17    3L2C   
SCOP (Structural Classification of Proteins)1E17    3L2C   
CATH (Classification of proteins structures)1E17    3L2C   
SuperfamilyP98177
Human Protein AtlasENSG00000184481
Peptide AtlasP98177
HPRD02070
IPIIPI00024316   IPI00220121   
Protein Interaction databases
DIP (DOE-UCLA)P98177
IntAct (EBI)P98177
FunCoupENSG00000184481
BioGRIDFOXO4
STRING (EMBL)FOXO4
ZODIACFOXO4
Ontologies - Pathways
QuickGOP98177
Ontology : AmiGORNA polymerase II transcription factor activity, sequence-specific DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  cytosol  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  cell cycle arrest  mitotic G2 DNA damage checkpoint  muscle organ development  beta-catenin binding  transcription factor binding  negative regulation of cell proliferation  insulin receptor signaling pathway  negative regulation of angiogenesis  enzyme binding  identical protein binding  sequence-specific DNA binding  positive regulation of transcription from RNA polymerase II promoter  stem cell differentiation  negative regulation of smooth muscle cell differentiation  negative regulation of G0 to G1 transition  positive regulation of cell cycle arrest  
Ontology : EGO-EBIRNA polymerase II transcription factor activity, sequence-specific DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  cytosol  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  cell cycle arrest  mitotic G2 DNA damage checkpoint  muscle organ development  beta-catenin binding  transcription factor binding  negative regulation of cell proliferation  insulin receptor signaling pathway  negative regulation of angiogenesis  enzyme binding  identical protein binding  sequence-specific DNA binding  positive regulation of transcription from RNA polymerase II promoter  stem cell differentiation  negative regulation of smooth muscle cell differentiation  negative regulation of G0 to G1 transition  positive regulation of cell cycle arrest  
Pathways : BIOCARTAAKT Signaling Pathway [Genes]    Ras Signaling Pathway [Genes]   
Pathways : KEGGRas signaling pathway    FoxO signaling pathway   
NDEx NetworkFOXO4
Atlas of Cancer Signalling NetworkFOXO4
Wikipedia pathwaysFOXO4
Orthology - Evolution
OrthoDB4303
GeneTree (enSembl)ENSG00000184481
Phylogenetic Trees/Animal Genes : TreeFamFOXO4
Homologs : HomoloGeneFOXO4
Homology/Alignments : Family Browser (UCSC)FOXO4
Gene fusions - Rearrangements
Fusion : MitelmanCIC/FOXO4 [19q13.2/Xq13.1]  [t(X;19)(q13;q13)]  
Fusion : MitelmanPAX3/FOXO4 [2q36.1/Xq13.1]  [t(X;2)(q13;q36)]  
Fusion : COSMICKMT2A [11q23.3]  -  FOXO4 [Xq13.1]  [fusion_1976]  
Polymorphisms : SNP, variants
NCBI Variation ViewerFOXO4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FOXO4
dbVarFOXO4
ClinVarFOXO4
1000_GenomesFOXO4 
Exome Variant ServerFOXO4
ExAC (Exome Aggregation Consortium)FOXO4 (select the gene name)
Genetic variants : HAPMAP4303
Genomic Variants (DGV)FOXO4 [DGVbeta]
Mutations
ICGC Data PortalFOXO4 
TCGA Data PortalFOXO4 
Broad Tumor PortalFOXO4
OASIS PortalFOXO4 [ Somatic mutations - Copy number]
Cancer Gene: CensusFOXO4 
Somatic Mutations in Cancer : COSMICFOXO4 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)X-chromosome gene database
BioMutasearch FOXO4
DgiDB (Drug Gene Interaction Database)FOXO4
DoCM (Curated mutations)FOXO4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)FOXO4 (select a term)
intoGenFOXO4
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)X:70315999-70323384  ENSG00000184481
CONAN: Copy Number AnalysisFOXO4 
Mutations and Diseases : HGMDFOXO4
OMIM300033   
MedgenFOXO4
Genetic Testing Registry FOXO4
NextProtP98177 [Medical]
TSGene4303
GENETestsFOXO4
Huge Navigator FOXO4 [HugePedia]
snp3D : Map Gene to Disease4303
BioCentury BCIQFOXO4
ClinGenFOXO4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4303
Chemical/Pharm GKB GenePA162388882
Clinical trialFOXO4
Miscellaneous
canSAR (ICR)FOXO4 (select the gene name)
Probes
Litterature
PubMed84 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineFOXO4
EVEXFOXO4
GoPubMedFOXO4
iHOPFOXO4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Sep 19 19:25:50 CEST 2016

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