The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MTMR2  -  myotubularin related protein 2

Homo sapiens

Synonyms: CMT4B, CMT4B1, KIAA1073, Myotubularin-related protein 2, Phosphatidylinositol-3,5-bisphosphate 3-phosphatase, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of MTMR2


High impact information on MTMR2

  • A gene mutated in Charcot-Marie-Tooth disease type 4B (CMT4B), an autosomal recessive demyelinating neuropathy with myelin outfoldings, has been mapped on chromosome 11q22 [5].
  • Finally, the MTMR2 structure will serve as a model for other members of the myotubularin family and provide a framework for understanding the mechanism whereby mutations in these proteins lead to disease [3].
  • Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization [6].
  • Mutations in the myotubularin (MTM)-related protein 2 (MTMR2) gene are responsible for the severe autosomal recessive neuropathy Charcot-Marie-Tooth disease type 4B1 [7].
  • Our data indicate that phosphoinositide-protein interactions, as well as protein-protein interactions, are necessary for the correct regulation of MTMR2 [7].

Chemical compound and disease context of MTMR2


Biological context of MTMR2


Anatomical context of MTMR2

  • We demonstrate that the known disease-associated MTMR2 mutations lead to dramatically reduced phosphatase activity, suggesting that the MTMR2 phosphatase activity is crucial for the proper function of peripheral nerves in CMT4B1 [1].
  • The neurofilament light chain protein, NF-L, was identified repeatedly in both screenings, and found to interact with MTMR2 in both Schwann cells and neurons [12].

Associations of MTMR2 with chemical compounds


Other interactions of MTMR2

  • MTM1 is a phosphatidylinositol phosphatase with reported specificity toward PtdIns3P, while the related proteins MTMR2 and MTMR3 hydrolyze both PtdIns3P and PtdIns(3,5)P2 [8].
  • All active MTMs we have tested (MTM1, MTMR2-MTMR4) reduce endosomal PtdIns3P levels upon overexpression [15].
  • One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1 [16].
  • Exclusion of the SCN2B gene as candidate for CMT4B [17].

Analytical, diagnostic and therapeutic context of MTMR2

  • To investigate whether mutations in MTMR2 may also cause different forms of CMT, we screened 183 unrelated patients with a broad spectrum of CMT and related neuropathies using denaturing high-performance liquid chromatography [18].
  • An animal model for CMT4B would provide insights into the pathogenesis of this disorder [10].


  1. Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1. Berger, P., Bonneick, S., Willi, S., Wymann, M., Suter, U. Hum. Mol. Genet. (2002) [Pubmed]
  2. The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a membrane-associated pseudophosphatase also mutated in type 4B Charcot-Marie-Tooth disease. Robinson, F.L., Dixon, J.E. J. Biol. Chem. (2005) [Pubmed]
  3. Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Begley, M.J., Taylor, G.S., Kim, S.A., Veine, D.M., Dixon, J.E., Stuckey, J.A. Mol. Cell (2003) [Pubmed]
  4. Localization of a gene responsible for autosomal recessive demyelinating neuropathy with focally folded myelin sheaths to chromosome 11q23 by homozygosity mapping and haplotype sharing. Bolino, A., Brancolini, V., Bono, F., Bruni, A., Gambardella, A., Romeo, G., Quattrone, A., Devoto, M. Hum. Mol. Genet. (1996) [Pubmed]
  5. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Bolino, A., Muglia, M., Conforti, F.L., LeGuern, E., Salih, M.A., Georgiou, D.M., Christodoulou, K., Hausmanowa-Petrusewicz, I., Mandich, P., Schenone, A., Gambardella, A., Bono, F., Quattrone, A., Devoto, M., Monaco, A.P. Nat. Genet. (2000) [Pubmed]
  6. Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase. Kim, S.A., Vacratsis, P.O., Firestein, R., Cleary, M.L., Dixon, J.E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module. Berger, P., Schaffitzel, C., Berger, I., Ban, N., Suter, U. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases. Schaletzky, J., Dove, S.K., Short, B., Lorenzo, O., Clague, M.J., Barr, F.A. Curr. Biol. (2003) [Pubmed]
  9. Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15. Senderek, J., Bergmann, C., Weber, S., Ketelsen, U.P., Schorle, H., Rudnik-Schöneborn, S., Büttner, R., Buchheim, E., Zerres, K. Hum. Mol. Genet. (2003) [Pubmed]
  10. Molecular characterization and expression analysis of Mtmr2, mouse homologue of MTMR2, the Myotubularin-related 2 gene, mutated in CMT4B. Bolino, A., Marigo, V., Ferrera, F., Loader, J., Romio, L., Leoni, A., Di Duca, M., Cinti, R., Cecchi, C., Feltri, M.L., Wrabetz, L., Ravazzolo, R., Monaco, A.P. Gene (2002) [Pubmed]
  11. Genetic evaluation of inherited motor/sensory neuropathy. Chance, P.F. Supplements to Clinical neurophysiology. (2004) [Pubmed]
  12. Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve. Previtali, S.C., Zerega, B., Sherman, D.L., Brophy, P.J., Dina, G., King, R.H., Salih, M.M., Feltri, L., Quattrini, A., Ravazzolo, R., Wrabetz, L., Monaco, A.P., Bolino, A. Hum. Mol. Genet. (2003) [Pubmed]
  13. Molecular basis for substrate recognition by MTMR2, a myotubularin family phosphoinositide phosphatase. Begley, M.J., Taylor, G.S., Brock, M.A., Ghosh, P., Woods, V.L., Dixon, J.E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  14. A novel homozygous missense mutation in the myotubularin-related protein 2 gene associated with recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheaths. Nelis, E., Erdem, S., Tan, E., Löfgren, A., Ceuterick, C., De Jonghe, P., Van Broeckhoven, C., Timmerman, V., Topaloglu, H. Neuromuscul. Disord. (2002) [Pubmed]
  15. Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosomerelated functions. Lorenzo, O., Urbé, S., Clague, M.J. J. Cell. Sci. (2006) [Pubmed]
  16. Clinicopathological and genetic study of early-onset demyelinating neuropathy. Parman, Y., Battaloglu, E., Baris, I., Bilir, B., Poyraz, M., Bissar-Tadmouri, N., Williams, A., Ammar, N., Nelis, E., Timmerman, V., De Jonghe, P., Necefov, A., Deymeer, F., Serdaroglu, P., Brophy, P.J., Said, G. Brain (2004) [Pubmed]
  17. Exclusion of the SCN2B gene as candidate for CMT4B. Bolino, A., Seri, M., Caroli, F., Eubanks, J., Srinivasan, J., Mandich, P., Schenone, A., Quattrone, A., Romeo, G., Catterall, W.A., Devoto, M. Eur. J. Hum. Genet. (1998) [Pubmed]
  18. Denaturing high-performance liquid chromatography of the myotubularin-related 2 gene (MTMR2) in unrelated patients with Charcot-Marie-Tooth disease suggests a low frequency of mutation in inherited neuropathy. Bolino, A., Lonie, L.J., Zimmer, M., Boerkoel, C.F., Takashima, H., Monaco, A.P., Lupski, J.R. Neurogenetics (2001) [Pubmed]
WikiGenes - Universities