RUNX1T1 (runt-related transcription factor 1; translocated to, 1 (cyclin D-related))

1997-10-01   Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
8q21.3
IMAGE
Atlas Image
LEGEND
ETO (8q22) in normal cells: clone dJ1155L8 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
AML1-MTG8,AML1T1,CBFA2T1,CDR,ETO,MTG8,ZMYND2
FUSION GENES

DNA/RNA

Transcription

from telomere to centromere; alternate slicing at the 5 end -> MTG8A and MTG8B

Proteins

Atlas Image
Protein Diagram

Description

577 or 604 amino acids ( MTG8A and MTG8B respectively), with a different N-term; 3 proline rich domains (as in transcription factors), 2 of which being also serine and threonine rich (as phosphorylation sites) and 2 Zn fingers (cys.cys/cys.cys and cys.cys/his.cys), a PEST region at the C terminus (conferring rapid intracellular degradation)

Expression

mainly in the brain; not in hematopoietic cells (debated)

Localisation

nuclear (probable)

Function

putative transcription factor

Homology

99% identical to the murine homolog

Implicated in

Entity name
Disease
AML, M2 mostly
Prognosis
CR is obtained; median survival (1.5-2 yrs) is the range with other AML or relatively better
Cytogenetics
additional anomalies are frequent: loss of Y or X chromosome, del(7q)/-7, +8, del (9q); complex t(8;21;Var) are known and have revealed that the crucial event lies on der(8); in agrement with the fact that both genes are transcribed from telomere to centromere
Hybrid gene
5 AML1 - 3 ETO
Fusion protein
N-term AML1 with the Runt domain fused to the nearly entire ETO
Oncogenesis
the fusion protein retain the ability to recognize the AML1 concensus binding site (--> negative dominant competitor with the normal AML1) and to dimerize with the cbtb/CBTB subunit --> probable altered transcriptional regulation of normal AML1 target genes

Other Information

Locus ID:

NCBI: 862
MIM: 133435
HGNC: 1535
Ensembl: ENSG00000079102

Variants:

dbSNP: 862
ClinVar: 862
TCGA: ENSG00000079102
COSMIC: RUNX1T1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000079102ENST00000265814Q06455
ENSG00000079102ENST00000360348Q06455
ENSG00000079102ENST00000360348W8FW32
ENSG00000079102ENST00000396218Q06455
ENSG00000079102ENST00000422361Q06455
ENSG00000079102ENST00000422361W8FW32
ENSG00000079102ENST00000436581A0A0A0MSU1
ENSG00000079102ENST00000517792E5RH30
ENSG00000079102ENST00000517919E7EQW7
ENSG00000079102ENST00000518317E5RJE7
ENSG00000079102ENST00000518361H0YC43
ENSG00000079102ENST00000518449E7EV92
ENSG00000079102ENST00000518823E5RI38
ENSG00000079102ENST00000518832E5RH72
ENSG00000079102ENST00000518844Q06455
ENSG00000079102ENST00000518954E7EX23
ENSG00000079102ENST00000518992E7ETA8
ENSG00000079102ENST00000519061E5RFQ3
ENSG00000079102ENST00000519422E7EQJ1
ENSG00000079102ENST00000519577E7EQJ1
ENSG00000079102ENST00000519847E7EWJ9
ENSG00000079102ENST00000520428E7EQ59
ENSG00000079102ENST00000520556E5RK76
ENSG00000079102ENST00000520583A0A1B0GX92
ENSG00000079102ENST00000520724Q06455
ENSG00000079102ENST00000520974E7ERJ9
ENSG00000079102ENST00000520978H0YBA6
ENSG00000079102ENST00000521054E5RG85
ENSG00000079102ENST00000521319E5RJB3
ENSG00000079102ENST00000521375E7EQI9
ENSG00000079102ENST00000521553E5RHJ8
ENSG00000079102ENST00000521733E5RJ32
ENSG00000079102ENST00000521751H0YC25
ENSG00000079102ENST00000521897E7EQJ1
ENSG00000079102ENST00000522467E7EQW3
ENSG00000079102ENST00000523168E7ESA9
ENSG00000079102ENST00000523629Q06455
ENSG00000079102ENST00000524215E7ESL1
ENSG00000079102ENST00000613302Q06455
ENSG00000079102ENST00000613886Q06455
ENSG00000079102ENST00000614812Q06455
ENSG00000079102ENST00000615601A0A087WWT6
ENSG00000079102ENST00000617740Q06455

Expression (GTEx)

0
5
10
15
20
25
30
35
40

Pathways

PathwaySourceExternal ID
Acute myeloid leukemiaKEGGko05221
Pathways in cancerKEGGhsa05200
Acute myeloid leukemiaKEGGhsa05221
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
179966492007Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein.130
168920372006A previously unidentified alternatively spliced isoform of t(8;21) transcript promotes leukemogenesis.124
217647522011The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation.85
153338392004E protein silencing by the leukemogenic AML1-ETO fusion protein.77
223437332012Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding.65
222017942012RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis.59
232234322013Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway.58
224987362012PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential.52
166163312006The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity.51
181561642008AML1-ETO reprograms hematopoietic cell fate by downregulating scl expression.47

Citation

Jean-Loup Huret

RUNX1T1 (runt-related transcription factor 1; translocated to, 1 (cyclin D-related))

Atlas Genet Cytogenet Oncol Haematol. 1997-10-01

Online version: http://atlasgeneticsoncology.org/gene/26/runx1t1