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

Article 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
380374602024CBP-mediated FOXO4 acetylation facilitates postmenopausal osteoporosis (PMO) progression through the inhibition of the Wnt/β-catenin signaling pathway.0
380374602024CBP-mediated FOXO4 acetylation facilitates postmenopausal osteoporosis (PMO) progression through the inhibition of the Wnt/β-catenin signaling pathway.0
378610002023Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.1
378610002023Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.1
349548732022Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53.6
360426282022Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma.0
367002132022The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease.3
349548732022Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53.6
360426282022Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma.0
367002132022The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease.3
328473772021Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective.25
332112212021miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression.3
334630542021Hypoxia-induced FOXO4/LDHA axis modulates gastric cancer cell glycolysis and progression.23
335770162021Deacetylation of FOXO4 by Sirt1 stabilizes chondrocyte extracellular matrix upon activating SOX9.7
336498372021lncRNA MEG3 inhibits pituitary tumor development by participating in cell proliferation, apoptosis and EMT processes.7

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/tumors-explorer/css/lib/js/_common.js

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