Gene Symbol: Mtm1
Description: X-linked myotubular myopathy gene 1
Alias: AF073996, Mtm, mKIAA4176, myotubularin, phosphatidylinositol-3,5-bisphosphate 3-phosphatase, phosphatidylinositol-3-phosphate phosphatase
Species: mouse
Products:     Mtm1

Top Publications

  1. Lawlor M, Read B, Edelstein R, Yang N, Pierson C, Stein M, et al. Inhibition of activin receptor type IIB increases strength and lifespan in myotubularin-deficient mice. Am J Pathol. 2011;178:784-93 pubmed publisher
    X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by deficiency of the lipid phosphatase, myotubularin. Patients with XLMTM often have severe perinatal weakness that requires mechanical ventilation to prevent death from ..
  2. Hnia K, Tronchère H, Tomczak K, Amoasii L, Schultz P, Beggs A, et al. Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle. J Clin Invest. 2011;121:70-85 pubmed publisher
    ..Here, we demonstrate that myotubularin (MTM1), which is mutated in individuals with X-linked centronuclear myopathy (XLCNM; also known as myotubular ..
  3. Laporte J, Blondeau F, Gansmuller A, Lutz Y, Vonesch J, Mandel J. The PtdIns3P phosphatase myotubularin is a cytoplasmic protein that also localizes to Rac1-inducible plasma membrane ruffles. J Cell Sci. 2002;115:3105-17 pubmed
    b>Myotubularin, the phosphatase mutated in X-linked myotubular myopathy, was shown to dephosphorylate phosphatidylinositol 3-monophosphate (PtdIns3P) and was also reported to interact with nuclear transcriptional regulators from the ..
  4. Pierson C, Dulin Smith A, Durban A, Marshall M, Marshall J, Snyder A, et al. Modeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype. Hum Mol Genet. 2012;21:811-25 pubmed publisher
    ..disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin. The Mtm1 knockout (KO) mouse has a severe phenotype and its short lifespan (8 weeks) makes it a challenge to ..
  5. Al Qusairi L, Weiss N, Toussaint A, Berbey C, Messaddeq N, Kretz C, et al. T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase. Proc Natl Acad Sci U S A. 2009;106:18763-8 pubmed publisher
    ..myopathy (XLMTM), a severe congenital disorder due to loss of function mutations in the MTM1 gene, encoding myotubularin, a phosphoinositide phosphatase thought to have a role in plasma membrane homeostasis and endocytosis...
  6. Zhang Y, Maksakova I, Gagnier L, van de Lagemaat L, Mager D. Genome-wide assessments reveal extremely high levels of polymorphism of two active families of mouse endogenous retroviral elements. PLoS Genet. 2008;4:e1000007 pubmed publisher
    ..These extreme levels of polymorphism suggest that ERV insertions play a significant role in genetic drift of mouse lines...
  7. Buj Bello A, Fougerousse F, Schwab Y, Messaddeq N, Spehner D, Pierson C, et al. AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis. Hum Mol Genet. 2008;17:2132-43 pubmed publisher
    Myotubular myopathy (XLMTM, OMIM 310400) is a severe congenital muscular disease due to mutations in the myotubularin gene (MTM1) and characterized by the presence of small myofibers with frequent occurrence of central nuclei...
  8. Chaussade C, Pirola L, Bonnafous S, Blondeau F, Brenz Verca S, Tronchère H, et al. Expression of myotubularin by an adenoviral vector demonstrates its function as a phosphatidylinositol 3-phosphate [PtdIns(3)P] phosphatase in muscle cell lines: involvement of PtdIns(3)P in insulin-stimulated glucose transport. Mol Endocrinol. 2003;17:2448-60 pubmed
    ..myopathy is a muscle disorder caused by mutations on the myotubular myopathy-1 (MTM-1) gene, coding for myotubularin a 65-kDa polypeptide similar to protein phosphatases...
  9. Buj Bello A, Laugel V, Messaddeq N, Zahreddine H, Laporte J, Pellissier J, et al. The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice. Proc Natl Acad Sci U S A. 2002;99:15060-5 pubmed
    b>Myotubularin is a ubiquitously expressed phosphatase that acts on phosphatidylinositol 3-monophosphate [PI(3)P], a lipid implicated in intracellular vesicle trafficking and autophagy...

More Information


  1. Blewitt M, Gendrel A, Pang Z, Sparrow D, Whitelaw N, Craig J, et al. SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nat Genet. 2008;40:663-9 pubmed publisher
    ..This finding links a group of proteins normally associated with structural aspects of chromosome biology with epigenetic gene silencing. ..
  2. Jungbluth H, Sewry C, Buj Bello A, Kristiansen M, Ørstavik K, Kelsey A, et al. Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation. Neuromuscul Disord. 2003;13:55-9 pubmed
    X-linked myotubular myopathy is a severe congenital myopathy in males, caused by mutations in the myotubularin (MTM1) gene on chromosome Xq28. In heterozygous carriers of MTM1 mutations, clinical symptoms are usually absent or only mild...
  3. Raess M, Cowling B, Bertazzi D, Kretz C, Rinaldi B, Xuereb J, et al. Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy. Hum Mol Genet. 2017;26:3736-3748 pubmed publisher
    ..Loss-of-function mutations in MTM1 cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while ..
  4. Sabha N, Volpatti J, Gonorazky H, Reifler A, Davidson A, Li X, et al. PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models. J Clin Invest. 2016;126:3613-25 pubmed publisher
    ..neuromuscular disorder of phosphoinositide (PIP) metabolism resulting from mutations of the PIP phosphatase MTM1 for which there are no treatments...
  5. Fetalvero K, Yu Y, Goetschkes M, Liang G, Valdez R, Gould T, et al. Defective autophagy and mTORC1 signaling in myotubularin null mice. Mol Cell Biol. 2013;33:98-110 pubmed publisher compromised in mice deficient in the X-linked myotubular myopathy (XLMTM)-associated PtdIns(3)P phosphatase myotubularin (MTM1)...
  6. Agrawal P, Pierson C, Joshi M, Liu X, Ravenscroft G, Moghadaszadeh B, et al. SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet. 2014;95:218-26 pubmed publisher
    ..X-linked myotubular myopathy, the most common severe form of CNM, is caused by mutations in MTM1, encoding myotubularin (MTM1), a lipid phosphatase...
  7. Al Qusairi L, Prokic I, Amoasii L, Kretz C, Messaddeq N, Mandel J, et al. Lack of myotubularin (MTM1) leads to muscle hypotrophy through unbalanced regulation of the autophagy and ubiquitin-proteasome pathways. FASEB J. 2013;27:3384-94 pubmed publisher
    Mutations in the phosphoinositide phosphatase myotubularin (MTM1) results in X-linked myotubular/centronuclear myopathy (XLMTM), characterized by a severe decrease in muscle mass and strength in patients and murine models...
  8. Royer B, Hnia K, Gavriilidis C, Tronchère H, Tosch V, Laporte J. The myotubularin-amphiphysin 2 complex in membrane tubulation and centronuclear myopathies. EMBO Rep. 2013;14:907-15 pubmed publisher
    b>Myotubularin (MTM1) and amphiphysin 2 (BIN1) are two proteins mutated in different forms of centronuclear myopathy, but the functional and pathological relationship between these two proteins was unknown...
  9. Laporte J, Blondeau F, Buj Bello A, Tentler D, Kretz C, Dahl N, et al. Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human. Hum Mol Genet. 1998;7:1703-12 pubmed
    ..The corresponding protein, myotubularin, contains the consensus active site of tyrosine phosphatases (PTP) but otherwise shows no homology to other ..
  10. Mariot V, Joubert R, Hourde C, Feasson L, Hanna M, Muntoni F, et al. Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches. Nat Commun. 2017;8:1859 pubmed publisher
    ..We also provide in vivo evidence in the congenital myotubular myopathy mouse model (knock-out for the myotubularin coding gene Mtm1) that a down-regulated myostatin pathway can be reactivated by correcting the underlying gene ..
  11. Mansour R, Severin S, Xuereb J, Gratacap M, Laporte J, Buj Bello A, et al. Expression of myotubularins in blood platelets: Characterization and potential diagnostic of X-linked myotubular myopathy. Biochem Biophys Res Commun. 2016;476:167-73 pubmed publisher
    ..Members of this family are mutated in genetic diseases including myotubularin 1 (MTM1) and myotubularin-related protein 2 (MTMR2) which mutations are responsible of X-linked centronuclear ..
  12. Lawlor M, Viola M, Meng H, Edelstein R, Liu F, Yan K, et al. Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice. Am J Pathol. 2014;184:1831-42 pubmed publisher
    X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure...
  13. Childers M, Joubert R, Poulard K, Moal C, Grange R, Doering J, et al. Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy. Sci Transl Med. 2014;6:220ra10 pubmed publisher
    Loss-of-function mutations in the myotubularin gene (MTM1) cause X-linked myotubular myopathy (XLMTM), a fatal, congenital pediatric disease that affects the entire skeletal musculature...
  14. Amoasii L, Hnia K, Chicanne G, Brech A, Cowling B, Müller M, et al. Myotubularin and PtdIns3P remodel the sarcoplasmic reticulum in muscle in vivo. J Cell Sci. 2013;126:1806-19 pubmed publisher
    ..In this study, we identified myotubularin (MTM1), a phosphoinositide phosphatase mutated in X-linked centronuclear myopathy (XLCNM, or myotubular ..
  15. Joubert R, Vignaud A, Le M, Moal C, Messaddeq N, Buj Bello A. Site-specific Mtm1 mutagenesis by an AAV-Cre vector reveals that myotubularin is essential in adult muscle. Hum Mol Genet. 2013;22:1856-66 pubmed publisher loss-of-function mutations in the MTM1 gene, have been generated by homologous recombination and shown that myotubularin is essential for skeletal muscle...
  16. Lawlor M, ARMSTRONG D, Viola M, Widrick J, Meng H, Grange R, et al. Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy. Hum Mol Genet. 2013;22:1525-38 pubmed publisher
    ..myotubular myopathy (XLMTM), a fatal congenital muscle disease caused by deficiency of the lipid phosphatase, myotubularin. The Mtm1?4 and Mtm1 p...
  17. Amoasii L, Bertazzi D, Tronchère H, Hnia K, Chicanne G, Rinaldi B, et al. Phosphatase-dead myotubularin ameliorates X-linked centronuclear myopathy phenotypes in mice. PLoS Genet. 2012;8:e1002965 pubmed publisher
    b>Myotubularin MTM1 is a phosphoinositide (PPIn) 3-phosphatase mutated in X-linked centronuclear myopathy (XLCNM; myotubular myopathy). We investigated the involvement of MTM1 enzymatic activity on XLCNM phenotypes...
  18. Lawlor M, Alexander M, Viola M, Meng H, Joubert R, Gupta V, et al. Myotubularin-deficient myoblasts display increased apoptosis, delayed proliferation, and poor cell engraftment. Am J Pathol. 2012;181:961-8 pubmed publisher
    X-linked myotubular myopathy is a severe congenital myopathy caused by deficiency of the lipid phosphatase, myotubularin. Recent studies of human tissue and animal models have discovered structural and physiological abnormalities in ..
  19. Dowling J, Joubert R, Low S, Durban A, Messaddeq N, Li X, et al. Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models. Dis Model Mech. 2012;5:852-9 pubmed publisher
    Myotubular myopathy (MTM) is a severe congenital muscle disease characterized by profound weakness, early respiratory failure and premature lethality...
  20. Concepcion D, Flores García L, Hamilton B. Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing. PLoS Genet. 2009;5:e1000484 pubmed publisher