ZMYM2 (fused in myeloproliferative disorders).

2001-01-01   Marie-Joséphe Pébusque 

Identity

HGNC
LOCATION
13q12.11
IMAGE
Atlas Image
LEGEND
FIM (13q12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
FIM,MYM,RAMP,SCLL,ZNF198
FUSION GENES

DNA/RNA

Description

full length cDNA: 5,016 bp; a single open reading frame of 4,137 bp; alternative spliced cDNA variant

Transcription

main transcripts: 5.0 and 7.5 kb

Proteins

Atlas Image

Description

1 379 amino acids; hydrophobic protein containing several motifs: a N-terminal cystein-rich region containing ten repeats with the consensus sequence C-X2-C-X18-24-F/Y-C-X3-C, which correspond to a novel zinc finger motifs, a highly hydrophobic proline-rich stretch, and a bipartite nuclear localization signal

Expression

wide

Localisation

cell nucleus and nucleolus; within the nucleolus, colocalizes with UBF (Upstream Binding Factor)

Function

may be involved in the regulation of rRNA transcription

Homology

FIM is related to DXS6673E, a gene which may be related with mental retardation

Implicated in

Entity name
t(8;13)(p12;q12)/AML-NHL --> 5 ZMYM2 - 3 FGFR1 ; stem-cell myeloproliferative disorder associated with the 8p12 chromosomal translocations; fused to the catalytic domain of FGFR1
Disease
stem-cell myeloproliferative disorder characterized by myeloid hyperplasia, T -cell lymphoblastic leukemia/lymphoma and peripheral blood eosinophilia, and it generally progresses to acute myeloid leukemia; specific to the 8p12 chromosomal region
Prognosis
very poor (median survival: 12 mths)
Cytogenetics
usually, t(8;13)(p12;q12) occurs as a single anomaly; duplication of the der(13) was found during disease progression, suggesting that the crucial event might lie on this derivative chromosome; additional abnormalities:+8, +21
Hybrid gene
5 FIM - 3 FGFR1; localisation: der(13)
Atlas Image
DNA Diagram
Fusion protein
aberrant tyrosine kinase composed of the N-term two-thirds of FIM (retaining the 10 putative zinc finger motifs), and the FGFR1 intracellular region minus the major part of the juxtamembrane domain
Oncogenesis
constitutive kinase activity of FGFR1 through constitutive activation of FGFR1 signal transduction pathways via constitutive dimerization capability mediated by the FIM N-term zinc finger sequences

Bibliography

Pubmed IDLast YearTitleAuthors
104809031999Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation.Ollendorff V et al
95769491998Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13).Popovici C et al
94994161998The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP.Smedley D et al
108871372000ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain.Xiao S et al
94259081998FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.Xiao S et al

Other Information

Locus ID:

NCBI: 7750
MIM: 602221
HGNC: 12989
Ensembl: ENSG00000121741

Variants:

dbSNP: 7750
ClinVar: 7750
TCGA: ENSG00000121741
COSMIC: ZMYM2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000121741ENST00000382871Q9UBW7
ENSG00000121741ENST00000382871A0A024RDS3
ENSG00000121741ENST00000382874Q9UBW7
ENSG00000121741ENST00000382874A0A024RDS3
ENSG00000121741ENST00000610343Q9UBW7
ENSG00000121741ENST00000610343A0A024RDS3
ENSG00000121741ENST00000620447A0A087X151

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Pathways

PathwaySourceExternal ID
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by FGFR in diseaseREACTOMER-HSA-1226099
Signaling by FGFR1 in diseaseREACTOMER-HSA-5655302
FGFR1 mutant receptor activationREACTOMER-HSA-1839124
Signaling by cytosolic FGFR1 fusion mutantsREACTOMER-HSA-1839117

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
258553822015PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis.35
188068732008ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers.33
214803202011Proteins ZNF198 and SUZ12 are down-regulated in hepatitis B virus (HBV) X protein-mediated hepatocyte transformation and in HBV replication.25
195062982009Genetic fingerprinting of the development and progression of T-cell lymphoma in a murine model of atypical myeloproliferative disorder initiated by the ZNF198-fibroblast growth factor receptor-1 chimeric tyrosine kinase.23
17389761200714-3-3 Integrates prosurvival signals mediated by the AKT and MAPK pathways in ZNF198-FGFR1-transformed hematopoietic cells.21
125942232003The oncogenic fusion protein-tyrosine kinase ZNF198/fibroblast growth factor receptor-1 has signaling function comparable with interleukin-6 cytokine receptors.17
170277522006ZNF198, a zinc finger protein rearranged in myeloproliferative disease, localizes to the PML nuclear bodies and interacts with SUMO-1 and PML.15
146606702004Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1.12
262833742015Screen for multi-SUMO-binding proteins reveals a multi-SIM-binding mechanism for recruitment of the transcriptional regulator ZMYM2 to chromatin.12

Citation

Marie-Joséphe Pébusque

ZMYM2 (fused in myeloproliferative disorders).

Atlas Genet Cytogenet Oncol Haematol. 2001-01-01

Online version: http://atlasgeneticsoncology.org/gene/114/zmym2-(fused-in-myeloproliferative-disorders)

Historical Card

1998-03-01 ZMYM2 (fused in myeloproliferative disorders). by  Jean-Loup Huret,Dominique Leroux 

Lymphoma Research Group - Groupe de Recherche sur les Lymphomes, Institut Albert Bonniot, La Tronche 38706, France (DL)