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

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

2001-08-01 Stig E. Bojesen Affiliation

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

Show Gene Fusions

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 ID	Last Year	Title	Authors
9010221	1997	Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23).	Borkhardt A et al
10217147	1999	Direct control of the Forkhead transcription factor AFX by protein kinase B.	Kops GJ et al
10783894	2000	AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.	Medema RH et al
7529552	1994	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 et al
9341872	1997	AFX1 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 ID	Transcript ID	Uniprot
ENSG00000184481	ENST00000341558	P98177
ENSG00000184481	ENST00000374259	P98177

Expression (GTEx)

0

10

20

30

40

50

60

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Ras signaling pathway	KEGG	hsa04014
FoxO signaling pathway	KEGG	hsa04068
Metabolism of proteins	REACTOME	R-HSA-392499
Post-translational protein modification	REACTOME	R-HSA-597592
Disease	REACTOME	R-HSA-1643685
Diseases of signal transduction	REACTOME	R-HSA-5663202
PI3K/AKT Signaling in Cancer	REACTOME	R-HSA-2219528
Constitutive Signaling by AKT1 E17K in Cancer	REACTOME	R-HSA-5674400
Immune System	REACTOME	R-HSA-168256
Adaptive Immune System	REACTOME	R-HSA-1280218
Signaling by the B Cell Receptor (BCR)	REACTOME	R-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)	REACTOME	R-HSA-1168372
PIP3 activates AKT signaling	REACTOME	R-HSA-1257604
AKT phosphorylates targets in the nucleus	REACTOME	R-HSA-198693
Innate Immune System	REACTOME	R-HSA-168249
DAP12 interactions	REACTOME	R-HSA-2172127
DAP12 signaling	REACTOME	R-HSA-2424491
Fc epsilon receptor (FCERI) signaling	REACTOME	R-HSA-2454202
Role of LAT2/NTAL/LAB on calcium mobilization	REACTOME	R-HSA-2730905
Signal Transduction	REACTOME	R-HSA-162582
Signaling by EGFR	REACTOME	R-HSA-177929
GAB1 signalosome	REACTOME	R-HSA-180292
Signalling by NGF	REACTOME	R-HSA-166520
NGF signalling via TRKA from the plasma membrane	REACTOME	R-HSA-187037
PI3K/AKT activation	REACTOME	R-HSA-198203
Signaling by PDGF	REACTOME	R-HSA-186797
Downstream signal transduction	REACTOME	R-HSA-186763
Signaling by SCF-KIT	REACTOME	R-HSA-1433557
Deubiquitination	REACTOME	R-HSA-5688426
Ub-specific processing proteases	REACTOME	R-HSA-5689880

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
38037460	2024	CBP-mediated FOXO4 acetylation facilitates postmenopausal osteoporosis (PMO) progression through the inhibition of the Wnt/β-catenin signaling pathway.	0
38037460	2024	CBP-mediated FOXO4 acetylation facilitates postmenopausal osteoporosis (PMO) progression through the inhibition of the Wnt/β-catenin signaling pathway.	0
37861000	2023	Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.	1
37861000	2023	Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons.	1
34954873	2022	Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53.	6
36042628	2022	Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma.	0
36700213	2022	The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease.	3
34954873	2022	Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53.	6
36042628	2022	Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma.	0
36700213	2022	The role of FOXO4/NFAT2 signaling pathway in dysfunction of human coronary endothelial cells and inflammatory infiltration of vasculitis in Kawasaki disease.	3
32847377	2021	Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective.	25
33211221	2021	miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression.	3
33463054	2021	Hypoxia-induced FOXO4/LDHA axis modulates gastric cancer cell glycolysis and progression.	23
33577016	2021	Deacetylation of FOXO4 by Sirt1 stabilizes chondrocyte extracellular matrix upon activating SOX9.	7
33649837	2021	lncRNA 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/case-report-explorer/img/js/lib/all.min.js

Historical Card

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

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