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

2001-08-01   Stig E. Bojesen 

Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark

Identity

HGNC
LOCATION
Xq13.1
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
AFX1 (ALL1 fused gene from chromosome X, 1),MLLT7 (myeloid/lymphoid leukemia translocated to, 7),AFX,FOXO4
FUSION GENES

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

Proteins

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

Entity name
t(X;11)(q13q23)/acute leukaemias --> KMT2A - FOXO4
Disease
AML, T-ALL
Prognosis
very poor
Hybrid gene
5 MLL-3 AFX as well as the reciprocal 5 AFX-3 MLL on DNA and mRNA level
Fusion protein
comprises about 1400 amino acids from N-term MLL and 354 amino acids from AFX C-term; the reciprocal may be expressed

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
90102211997Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23).Borkhardt A et al
102171471999Direct control of the Forkhead transcription factor AFX by protein kinase B.Kops GJ et al
107838942000AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.Medema RH et al
75295521994Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.Parry P et al
93418721997AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism.Peters U et al

Other Information

Locus ID:

NCBI: 4303
MIM: 300033
HGNC: 7139
Ensembl: ENSG00000184481

Variants:

dbSNP: 4303
ClinVar: 4303
TCGA: ENSG00000184481
COSMIC: FOXO4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000184481ENST00000341558P98177
ENSG00000184481ENST00000374259P98177

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
Ras signaling pathwayKEGGhsa04014
FoxO signaling pathwayKEGGhsa04068
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
Constitutive Signaling by AKT1 E17K in CancerREACTOMER-HSA-5674400
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
AKT phosphorylates targets in the nucleusREACTOMER-HSA-198693
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GAB1 signalosomeREACTOMER-HSA-180292
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
PI3K/AKT activationREACTOMER-HSA-198203
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by SCF-KITREACTOMER-HSA-1433557
DeubiquitinationREACTOMER-HSA-5688426
Ub-specific processing proteasesREACTOMER-HSA-5689880

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
159054042005Functional interaction between beta-catenin and FOXO in oxidative stress signaling.270
155383822004FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK.251
217081912011FoxO transcription factors; Regulation by AKT and 14-3-3 proteins.221
151265062004FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1).189
118845912002Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors.117
192442502009The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors.98
216138252011FoxO family members in cancer.68
158240872005FOXO-dependent expression of the proapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells.66
117779152002The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor.55
219340922011MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4.53

Citation

Stig E. Bojesen

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

Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

Online version: http://atlasgeneticsoncology.org/gene/57/foxo4

Historical Card

1998-04-01 FOXO4 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7) by  Olivier Bernard 

Unite Inserm U434, CNRS, Institut de Genetique Moleculaire, Paris, France