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Gene Review

ZMYM2  -  zinc finger, MYM-type 2

Homo sapiens

Synonyms: FIM, Fused in myeloproliferative disorders protein, MYM, RAMP, Rearranged in atypical myeloproliferative disorder protein, ...
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Disease relevance of ZMYM2


Psychiatry related information on ZMYM2

  • Woc is a Drosophila zinc finger protein that shares homology with the human polypeptides ZNF261 and ZNF198 implicated in mental retardation and leukemia syndromes [6].
  • As a result of the volume and cost development the direct detrimental effects of alcohol abuse grew from FIM 1.0-1.3 billion in 1980 to FIM 2.8-3.7 billion in 1990: i.e. a real increase of 51-56% in the direct costs of detrimental effects [7].
  • These outcomes were corroborated by results of the FIM and the Dementia Rating Scale [8].
  • Rehabilitation participation was a mediator of this association: greater depressive symptoms and cognitive impairment predicted poorer rehabilitation participation which, in turn, predicted lower motor FIM efficiency [9].
  • Despite similar functional status at inpatient rehabilitation discharge, Hispanic ethnicity was associated with poorer functional outcomes at 1 year postinjury (DRS, FIM, CIQ), after controlling for age, length of posttraumatic amnesia, injury severity, DRS score at admission, FIM score at admission, and preinjury educational level (P<.05) [10].

High impact information on ZMYM2


Chemical compound and disease context of ZMYM2


Biological context of ZMYM2

  • Exon trapping of a PAC that spanned the chromosome 13 translocation breakpoints led to the identification of a gene, ZNF198, that detected rearranged bands when used as a probe against Southern blots of patient DNA [18].
  • Sequencing of these products revealed that ZNF198 consists of 26 exons with the initiation codon located in exon 4 [19].
  • These observations support the idea that ZNF198, through its interaction with HHR6 and RAD18, may be involved in the DNA repair process [20].
  • These observations suggest that expression of the ZNF198/FGFR1 fusion gene is associated with specific PAI-2-mediated resistance to apoptosis which may contribute to the highly malignant nature of leukemic cells carrying this fusion kinase gene [12].
  • We used oligonucleotide microarrays to compare the gene-expression profiles between HEK-293 cells that stably express either the ZNF198/FGFR1 chimeric protein or the wild-type ZNF198 gene [12].

Anatomical context of ZMYM2

  • Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome [18].
  • To determine the transforming properties of this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL)-3 dependent cell line Ba/F3 [21].
  • Patients with combined lesions and more extensive brain injury had significantly higher FIM scores (P < 0.05) than patients with injury restricted to the basal ganglia/ internal capsule [22].
  • 3. Ramp stretches (0.5-8.6% sarcomere strain, confined to the plateau of the isometric tension-length relationship) were given at different velocities of lengthening (0.03-1.8 sarcomere lengths s-1) [23].
  • Hierarchical linear modeling of FIM instrument growth curve characteristics after spinal cord injury [24].

Associations of ZMYM2 with chemical compounds

  • Arsenic trioxide reduced STAT3 activation by Janus kinases, altered phosphorylation and electrophoretic mobility of ZNF198/fibroblast growth factor receptor 1, reduced kinase protein level, and decreased STAT3 protein phosphorylation [25].
  • The bactericidal effect of a combination of rifampin (Ramp) and trimethoprim (Tmp) was studied using dense cultures of test organisms, including some urinary pathogens, growing in human urine [26].
  • 5-fluorouracil, ifosfamide and mitomycin (FIM) combination for pancreatic-biliary tumors [27].
  • Using the muscle relaxant with the longest waiting time instead of that with the shortest waiting time (difference 21.8 min) cost more than FIM 800 (approximately $160) extra per patient [28].
  • Patients with CHF performed a maximal exercise test using a Ramp protocol before and after 6 months of therapy with either metoprolol or carvedilol [29].

Regulatory relationships of ZMYM2

  • We also show that forced expression of FIM inhibits the emergence of hematopoietic cells in the cultured mouse aorta-gonad-mesonephros (AGM) region on embryonic day (E) 11.5, where definitive hematopoiesis is first found during embryogenesis [30].

Other interactions of ZMYM2

  • Clones were identified in which the ZNF198 was fused to exon 9 of the fibroblast growth factor receptor-1 (FGFR1), a gene known to map to 8p11 [18].
  • We demonstrate here that the human RAD18 is also present in the ZNF198/HHR6 protein complex, although it does not coimmunoprecipitate with the fusion kinase [20].
  • Replacement of the ZNF198 portion by the Bcr portion as present in the t(8;22) translocation shifted the signaling toward a more prominent STAT5 activation [31].
  • The reciprocal t(8;13) chromosome translocation results in a fusion gene (FUS) in which the N-terminal half of the zinc finger protein ZNF198 is combined with the cytoplasmic domain of the fibroblast growth factor receptor-1 (FGFR1) [31].
  • These observations were confirmed using co-immunoprecipitation which demonstrated that ZNF198 is covalently modified by SUMO-1 [32].

Analytical, diagnostic and therapeutic context of ZMYM2


  1. FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Xiao, S., Nalabolu, S.R., Aster, J.C., Ma, J., Abruzzo, L., Jaffe, E.S., Stone, R., Weissman, S.M., Hudson, T.J., Fletcher, J.A. Nat. Genet. (1998) [Pubmed]
  2. The t(8;13) atypical myeloproliferative disorder: further analysis of the ZNF198 gene and lack of evidence for multiple genes disrupted on chromosome 13. Still, I.H., Cowell, J.K. Blood (1998) [Pubmed]
  3. A case of myelofibrosis with a t(4;13)(q25;q12): evidence for involvement of a second 13q12 locus in chronic myeloproliferative disorders. MacDonald, D.H., Lahiri, D., Chase, A., Sohal, J., Goldman, J.M., Cross, N.C. Br. J. Haematol. (1999) [Pubmed]
  4. Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13). Popovici, C., Adélaïde, J., Ollendorff, V., Chaffanet, M., Guasch, G., Jacrot, M., Leroux, D., Birnbaum, D., Pébusque, M.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Impact of osteoarthritis on rehabilitation for persons with hip fracture. Nguyen-Oghalai, T.U., Ottenbacher, K.J., Granger, C.V., Smith, S.T., Goodwin, J.S. Arthritis Rheum. (2006) [Pubmed]
  6. The putative Drosophila transcription factor woc is required to prevent telomeric fusions. Raffa, G.D., Cenci, G., Siriaco, G., Goldberg, M.L., Gatti, M. Mol. Cell (2005) [Pubmed]
  7. The costs of the detrimental effects of alcohol abuse have grown faster than alcohol consumption in Finland. Salomaa, J. Addiction (1995) [Pubmed]
  8. The minimally conscious state and recovery potential: a follow-up study 2 to 5 years after traumatic brain injury. Lammi, M.H., Smith, V.H., Tate, R.L., Taylor, C.M. Archives of physical medicine and rehabilitation. (2005) [Pubmed]
  9. Adverse effects of depression and cognitive impairment on rehabilitation participation and recovery from hip fracture. Lenze, E.J., Munin, M.C., Dew, M.A., Rogers, J.C., Seligman, K., Mulsant, B.H., Reynolds, C.F. International journal of geriatric psychiatry. (2004) [Pubmed]
  10. Functional outcomes from inpatient rehabilitation after traumatic brain injury: how do hispanics fare? Arango-Lasprilla, J.C., Rosenthal, M., Deluca, J., Cifu, D.X., Hanks, R., Komaroff, E. Archives of physical medicine and rehabilitation (2007) [Pubmed]
  11. PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Chen, J., Deangelo, D.J., Kutok, J.L., Williams, I.R., Lee, B.H., Wadleigh, M., Duclos, N., Cohen, S., Adelsperger, J., Okabe, R., Coburn, A., Galinsky, I., Huntly, B., Cohen, P.S., Meyer, T., Fabbro, D., Roesel, J., Banerji, L., Griffin, J.D., Xiao, S., Fletcher, J.A., Stone, R.M., Gilliland, D.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  12. Induction of the plasminogen activator inhibitor-2 in cells expressing the ZNF198/FGFR1 fusion kinase that is involved in atypical myeloproliferative disease. Kasyapa, C.S., Kunapuli, P., Hawthorn, L., Cowell, J.K. Blood (2006) [Pubmed]
  13. The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins. Demiroglu, A., Steer, E.J., Heath, C., Taylor, K., Bentley, M., Allen, S.L., Koduru, P., Brody, J.P., Hawson, G., Rodwell, R., Doody, M.L., Carnicero, F., Reiter, A., Goldman, J.M., Melo, J.V., Cross, N.C. Blood (2001) [Pubmed]
  14. Overexpression of the human erythrocyte glucose transporter occurs as a late event in human colorectal carcinogenesis and is associated with an increased incidence of lymph node metastases. Younes, M., Lechago, L.V., Lechago, J. Clin. Cancer Res. (1996) [Pubmed]
  15. Tizanidine for the treatment of intention myoclonus: a case series. Mukand, J.A., Giunti, E.J. Archives of physical medicine and rehabilitation. (2004) [Pubmed]
  16. Midodrine for the management of orthostatic hypotension in patients with spinal cord injury: A case report. Mukand, J., Karlin, L., Barrs, K., Lublin, P. Archives of physical medicine and rehabilitation. (2001) [Pubmed]
  17. Can forced-use therapy be clinically applied after stroke? An exploratory randomized controlled trial. Ploughman, M., Corbett, D. Archives of physical medicine and rehabilitation. (2004) [Pubmed]
  18. Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome. Reiter, A., Sohal, J., Kulkarni, S., Chase, A., Macdonald, D.H., Aguiar, R.C., Gonçalves, C., Hernandez, J.M., Jennings, B.A., Goldman, J.M., Cross, N.C. Blood (1998) [Pubmed]
  19. The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome. Kulkarni, S., Reiter, A., Smedley, D., Goldman, J.M., Cross, N.C. Genomics (1999) [Pubmed]
  20. ZNF198 protein, involved in rearrangement in myeloproliferative disease, forms complexes with the DNA repair-associated HHR6A/6B and RAD18 proteins. Kunapuli, P., Somerville, R., Still, I.H., Cowell, J.K. Oncogene (2003) [Pubmed]
  21. ANF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5. Smedley, D., Demiroglu, A., Abdul-Rauf, M., Heath, C., Cooper, C., Shipley, J., Cross, N.C. Neoplasia (1999) [Pubmed]
  22. Patients with stroke confined to basal ganglia have diminished response to rehabilitation efforts. Miyai, I., Blau, A.D., Reding, M.J., Volpe, B.T. Neurology (1997) [Pubmed]
  23. Storage and release of mechanical energy by contracting frog muscle fibres. Cavagna, G.A., Heglund, N.C., Harry, J.D., Mantovani, M. J. Physiol. (Lond.) (1994) [Pubmed]
  24. Hierarchical linear modeling of FIM instrument growth curve characteristics after spinal cord injury. Warschausky, S., Kay, J.B., Kewman, D.G. Archives of physical medicine and rehabilitation. (2001) [Pubmed]
  25. Arsenic Trioxide Affects Signal Transducer and Activator of Transcription Proteins through Alteration of Protein Tyrosine Kinase Phosphorylation. Wetzler, M., Brady, M.T., Tracy, E., Li, Z.R., Donohue, K.A., O'loughlin, K.L., Cheng, Y., Mortazavi, A., McDonald, A.A., Kunapuli, P., Wallace, P.K., Baer, M.R., Cowell, J.K., Baumann, H. Clin. Cancer Res. (2006) [Pubmed]
  26. Rifampin plus trimethoprim: bactericidal activity and suppression of resistance in human urine in vitro. Goldstein, B.P., Ripamonti, I.F., Bolzoni, G., Carniti, G., Arioli, V. Antimicrob. Agents Chemother. (1979) [Pubmed]
  27. 5-fluorouracil, ifosfamide and mitomycin (FIM) combination for pancreatic-biliary tumors. Abad, A., Rosell, R., Barnadas, A., Carles, J., Ribelles, N., Solano, V. Ann. Oncol. (1991) [Pubmed]
  28. The costs of intense neuromuscular block for anesthesia during endolaryngeal procedures due to waiting time. Puura, A.I., Rorarius, M.G., Manninen, P., Hopput, S., Baer, G.A. Anesth. Analg. (1999) [Pubmed]
  29. Decreased heart rate recovery after exercise in patients with congestive heart failure: effect of beta-blocker therapy. Racine, N., Blanchet, M., Ducharme, A., Marquis, J., Boucher, J.M., Juneau, M., White, M. J. Card. Fail. (2003) [Pubmed]
  30. Negative regulation of hematopoiesis by the fused in myeloproliferative disorders gene product. Inoue, H., Nobuhisa, I., Okita, K., Takizawa, M., Pébusque, M.J., Taga, T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  31. The oncogenic fusion protein-tyrosine kinase ZNF198/fibroblast growth factor receptor-1 has signaling function comparable with interleukin-6 cytokine receptors. Baumann, H., Kunapuli, P., Tracy, E., Cowell, J.K. J. Biol. Chem. (2003) [Pubmed]
  32. ZNF198, a zinc finger protein rearranged in myeloproliferative disease, localizes to the PML nuclear bodies and interacts with SUMO-1 and PML. Kunapuli, P., Kasyapa, C.S., Chin, S.F., Caldas, C., Cowell, J.K. Exp. Cell Res. (2006) [Pubmed]
  33. Mass spectroscopy identifies the splicing-associated proteins, PSF, hnRNP H3, hnRNP A2/B1, and TLS/FUS as interacting partners of the ZNF198 protein associated with rearrangement in myeloproliferative disease. Kasyapa, C.S., Kunapuli, P., Cowell, J.K. Exp. Cell Res. (2005) [Pubmed]
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