Affinage

MTM1

Myotubularin · UniProt Q13496

Length
603 aa
Mass
69.9 kDa
Annotated
2026-06-10
75 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTM1 encodes myotubularin, a phosphoinositide phosphatase whose loss-of-function mutations cause X-linked myotubular/centronuclear myopathy (PMID:9305655). Its core catalytic activity dephosphorylates PI3P, including a pool on EEA1-positive early endosomes whose accumulation upon MTM1 loss impairs Rab4-positive recycling-vesicle biogenesis, a defect reversed by depleting the upstream kinase PI3KC2β (PMID:39952567). Beyond clearing PI3P, MTM1 is the principal enzyme generating PI5P in muscle, feeding PI5P 4-kinase α to build the PI(4,5)P2 pool that concentrates in podosome-like protrusions driving myoblast fusion (PMID:38805272). These lipid functions underlie MTM1's role in muscle homeostasis: it maintains T-tubule integrity required for synchronous SR calcium release and excitation-contraction coupling (PMID:36408764), sits upstream of the IGF1R/Akt axis to balance autophagy and ubiquitin-proteasome activity (PMID:23695157), and is required to sustain adult myofiber architecture, mitochondrial and nuclear positioning, and neuromuscular function (PMID:23390130). MTM1 also acts in protein quality control as part of an MTM1-UBQLN2-HSP complex that routes misfolded desmin and vimentin to the proteasome before they aggregate (PMID:29358706). Catalytic-dissection studies show its lipid phosphatase activity is essential for rescue of muscle atrophy but dispensable for restoring T-tubule organization, indicating distinct phosphatase-dependent and -independent outputs (PMID:37490306). Orthologs extend this picture: C. elegans MTM-1 negatively regulates apoptotic corpse engulfment by dephosphorylating membrane PI3P upstream of the CED-5/CED-12/CED-10 GEF module (PMID:19816564, PMID:21490059), and the yeast ortholog functions as a mitochondrial manganese-trafficking factor required to activate SOD2 (PMID:12890866). In vertebrate liver, MTM1 localizes to Rab11-positive recycling endosomes and supports canalicular transporter trafficking and bile flux (PMID:37490339).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 Medium

    Identifying MTM1 as the gene mutated in X-linked myotubular myopathy and recognizing its tyrosine phosphatase domain established the founding hypothesis that an enzymatic phosphatase activity underlies the disease.

    Evidence Positional cloning and SSCP mutation screening in patients

    PMID:9305655

    Open questions at the time
    • Enzymatic activity inferred from domain homology, not demonstrated in vitro
    • No lipid substrate identified at this stage
  2. 2003 High

    The yeast ortholog revealed a mechanistically distinct function as a mitochondrial manganese carrier required for SOD2 activation, showing the MTM1 name covers divergent ortholog roles.

    Evidence Yeast deletion screen, SOD2 activity assays, manganese rescue, mitochondrial localization

    PMID:12890866

    Open questions at the time
    • Relationship to vertebrate phosphoinositide phosphatase function unresolved
    • Direct manganese-binding by the protein not shown
  3. 2009 High

    Genetic and lipid-level analysis in C. elegans defined MTM-1 as a PI3P phosphatase that negatively regulates apoptotic corpse engulfment, anchoring the lipid-phosphatase model in a whole-organism pathway.

    Evidence C. elegans genetics, epistasis with engulfment mutants, plasma-membrane PtdIns(3)P imaging

    PMID:19816564

    Open questions at the time
    • Direct in vitro phosphatase kinetics not measured
    • How phosphatase activity gates engulfment effectors unresolved
  4. 2011 High

    Epistasis placed MTM-1 upstream of the CED-2/CED-5/CED-12 GEF complex and linked CED-12 PH-domain binding of PtdIns(3,5)P2 to membrane recruitment, providing a substrate-to-effector mechanism for engulfment control.

    Evidence C. elegans epistasis, phagosome maturation assays, CED-12 PH-domain lipid pulldown

    PMID:21490059

    Open questions at the time
    • In vivo demonstration of MTM-1-driven CED-12 recruitment lacking
    • PtdIns(3,5)P2 vs PI3P substrate preference not quantified
  5. 2011 High

    A knock-in mouse showed the patient p.R69C allele acts largely by inducing exon 4 skipping with residual full-length protein, explaining a milder phenotype and linking myotubularin level to PI3P homeostasis.

    Evidence Knock-in mouse, mRNA splicing analysis, Western blot, muscle PI3P measurement

    PMID:22068590

    Open questions at the time
    • Generalizability to other missense alleles unknown
    • Threshold of activity needed for normal muscle not defined
  6. 2013 High

    Mtm1-null and AAV-rescue studies positioned MTM1 upstream of the IGF1R/Akt axis controlling the autophagy/proteasome balance, connecting the phosphatase to muscle proteostasis signaling.

    Evidence KO mouse, immunoblotting of pathway markers, autophagosome counts, AAV-Mtm1 rescue

    PMID:23695157

    Open questions at the time
    • Mechanism linking phosphoinositide turnover to IGF1R/Akt not defined
    • Direct phosphatase substrate driving this signaling unknown
  7. 2013 High

    Adult-specific conditional deletion established that myotubularin is continuously required in mature muscle, producing T-tubule defects, organelle mispositioning, and NMJ abnormalities rather than acting only during development.

    Evidence AAV-Cre conditional deletion, histology, EM, force measurement, marker immunostaining

    PMID:23390130

    Open questions at the time
    • Causal order among the multiple defects unresolved
    • Cell-autonomous vs systemic contributions not separated
  8. 2017 High

    Domain-swap and rescue experiments showed phosphoinositide phosphatase activity is the shared functional core, with an MTMR2 N-terminal extension accounting for paralog-specific differences and a short MTMR2 isoform substituting for MTM1.

    Evidence Yeast complementation, AAV MTMR2-isoform rescue in Mtm1 KO mice, domain deletion

    PMID:28934386

    Open questions at the time
    • Molecular function of the MTMR2 N-terminal extension undefined
    • Endogenous redundancy in humans not addressed
  9. 2017 Medium

    Patient muscle and myotube analysis distinguished primary from secondary defects, showing RyR1/HDAC4/microRNA changes are downstream consequences in mature muscle rather than the initiating lesion.

    Evidence Patient biopsy immunoblotting, microRNA quantification, patient myotube calcium imaging

    PMID:28007904

    Open questions at the time
    • No rescue experiment to confirm secondary nature
    • Primary trigger of these changes not identified
  10. 2018 High

    Discovery of the MTM1-UBQLN2-HSP complex revealed a phosphatase-independent role in cytoskeletal proteostasis, routing misfolded desmin and vimentin to the proteasome before aggregation.

    Evidence Reciprocal Co-IP, proteasome degradation assays, loss-of-function in muscle cells, EM of aggregates

    PMID:29358706

    Open questions at the time
    • Stoichiometry and assembly of the complex undefined
    • Whether substrate recognition requires MTM1 lipid binding unknown
  11. 2022 Medium

    Calcium-transient recording with modeling identified the disrupted T-tubular network as the primary cause of impaired SR calcium release, ranking T-tubule structure above RyR-level changes in the EC-coupling defect.

    Evidence Confocal calcium recordings in MTM1-deficient fibers, mathematical modeling of T-tubule propagation

    PMID:36408764

    Open questions at the time
    • No genetic rescue confirming causality
    • Lipid mechanism linking MTM1 loss to T-tubule disruption not shown here
  12. 2023 High

    A zebrafish model extended MTM1 function to liver, showing it acts on Rab11 recycling endosomes to traffic canalicular transporters and maintain bile flux, with dynamin-2 inhibition partially correcting the defect.

    Evidence Zebrafish KO, Rab11/transporter co-localization, hepatocyte-specific rescue, dynasore chemical rescue

    PMID:37490339

    Open questions at the time
    • Direct lipid substrate at canalicular endosomes not measured
    • Relevance to human hepatic phenotypes not established
  13. 2023 High

    Catalytic-dead rescue in a BIN1-CNM model dissected phosphatase-dependent (atrophy/hypotrophy) from phosphatase-independent (T-tubule and organelle organization) outputs of MTM1, and linked T-tubule rescue to dysferlin/caveolin normalization.

    Evidence AAV-MTM1 and phosphatase-dead mutant rescue in Bin1mck-/- mice, histology, T-tubule imaging, immunoblotting

    PMID:37490306

    Open questions at the time
    • Identity of the phosphatase-independent activity unresolved
    • How MTM1 cross-corrects a BIN1 defect mechanistically unclear
  14. 2024 High

    Lipidomics established MTM1 as the principal PI5P-producing enzyme in muscle, feeding PIP4Kα-generated PI(4,5)P2 into podosome-like protrusions that drive myoblast fusion, defining a synthetic rather than purely degradative lipid output.

    Evidence Lipid mass spectrometry in depleted myoblasts, PLP live imaging, fusion assays

    PMID:38805272

    Open questions at the time
    • In vivo contribution of this pathway to muscle regeneration not shown
    • Direct enzymatic route from MTM1 substrate to PI5P not fully traced
  15. 2025 High

    Endosomal mapping showed MTM1 dephosphorylates PI3P on EEA1-positive early endosomes to enable Rab4 recycling-vesicle biogenesis, with PI3KC2β identified as the opposing kinase whose depletion rescues the defect.

    Evidence Mtm1-KO muscle cells, compartment-specific PI3P imaging, Rab4 vesicle assay, PI3KC2β depletion rescue

    PMID:39952567

    Open questions at the time
    • Cargo identity of Rab4 vesicles in muscle undefined
    • Link between endosomal recycling defect and myopathy phenotype not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MTM1's distinct molecular activities — PI3P turnover, PI5P synthesis, and UBQLN2-mediated proteostasis — are coordinated and which is the proximal driver of human myopathy remains unresolved.
  • No unified mechanism linking lipid and proteostasis functions
  • Tissue-specific substrate map incomplete
  • Structural basis of substrate selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-397014 Muscle contraction 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-392499 Metabolism of proteins 1 R-HSA-9609507 Protein localization 1 R-HSA-9612973 Autophagy 1
Partners
PI3KC2ΒUBQLN2
Complex memberships
MTM1-UBQLN2-HSP complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 MTM1 encodes myotubularin, a protein with a tyrosine phosphatase domain (PTP); missense mutations affecting the predicted PTP domain are expected to inactivate the putative enzymatic activity, and the protein is highly conserved through evolution including yeast and C. elegans orthologs. Positional cloning, sequence analysis, single-strand conformation polymorphism (SSCP) mutation screening Human molecular genetics Medium 9305655
2003 Yeast MTM1 (YGR257c) is a mitochondrial carrier family member required for manganese-dependent activation of SOD2 (superoxide dismutase 2) in the mitochondrial matrix; loss of MTM1 causes SOD2 inactivation that is rescued only by high-dose manganese supplementation, establishing MTM1 as a manganese trafficking factor for mitochondrial SOD2. Yeast genetic screen (MTM1 deletion), SOD2 activity assays, manganese supplementation rescue experiments, mitochondrial localization studies Proceedings of the National Academy of Sciences of the United States of America High 12890866
2009 C. elegans MTM-1 (ortholog of human MTM1) is a negative regulator of apoptotic cell corpse engulfment; its lipid phosphatase activity dephosphorylates PtdIns(3)P on the plasma membrane in engulfing cells, and loss of mtm-1 accelerates cell corpse clearance through the CED-5/CED-12/CED-10 module and requires PI3Ks VPS-34 and PIKI-1. C. elegans genetics (loss-of-function mutants, RNAi, overexpression), epistasis analysis with engulfment pathway mutants, plasma membrane localization imaging, in vivo PtdIns(3)P level assessment PLoS genetics High 19816564
2011 C. elegans MTM-1 acts upstream of the ced-2/ced-5/ced-12 ternary GEF complex and parallel to mig-2 in regulating apoptotic cell corpse clearance; MTM-1 also promotes phagosome maturation potentially through CED-1 receptor recycling, and the CED-12 PH domain can bind PtdIns(3,5)P2 (a substrate of MTM-1 phosphatase activity), suggesting MTM-1 regulates CED-12 recruitment to the plasma membrane. C. elegans epistasis analysis, cell corpse quantification, phagosome maturation assays, lipid-binding domain pulldown (CED-12 PH domain binding to PtdIns(3,5)P2) Development (Cambridge, England) High 21490059
2013 Loss of myotubularin (MTM1) in murine muscle leads to activation of the IGF1R/Akt pathway (increased IGF1R and Akt levels), upregulation of atrogenes (ubiquitin-proteasome pathway), increased autophagosomes and autophagy markers (LC3, P62), and abnormal mTOR/FOXO3a phosphorylation; AAV-mediated re-delivery of Mtm1 rescued muscle mass and normalized these pathways, demonstrating MTM1 acts upstream of IGF1R/Akt and downstream on the autophagy/proteasome balance. Mtm1-null mouse model analysis, immunoblotting, autophagosome counting, AAV-mediated gene rescue, quantification of atrogene expression FASEB journal High 23695157
2013 Myotubularin is required for proper function of skeletal muscle during adulthood; conditional adult-specific deletion of Mtm1 via AAV-Cre causes myofiber atrophy, disorganization of mitochondria and nuclei, T-tubule defects, severe muscle weakness, and abnormalities in satellite cell number, autophagy markers, protein synthesis, and neuromuscular junction transmission. AAV-Cre conditional adult Mtm1 deletion in mouse muscle, histopathology, electron microscopy, muscle force measurement, immunostaining for satellite cells and autophagy/NMJ markers Human molecular genetics High 23390130
2018 MTM1 forms a complex with UBQLN2 and HSP proteins (MTM1-UBQLN2-HSP complex) that recognizes and guides misfolded intermediate filament proteins desmin and vimentin to the proteasome for degradation prior to aggregate formation, thereby maintaining cytoskeletal integrity in muscle cells. Co-immunoprecipitation (MTM1-UBQLN2 complex), in vitro and cell-based proteasome degradation assays, loss-of-function studies in muscle cells, electron microscopy of protein aggregates Nature cell biology High 29358706
2017 The N-terminal domain of MTMR2 (absent in MTM1) is responsible for functional differences between MTM1 and MTMR2; a short MTMR2 isoform lacking this N-terminal extension behaves similarly to MTM1 in yeast complementation and mouse rescue assays, and AAV-mediated expression of MTMR2 isoforms in Mtm1 KO mice ameliorates myopathic phenotype, demonstrating functional redundancy of phosphoinositide phosphatase activity. Yeast heterologous expression complementation, AAV-mediated gene delivery in Mtm1 KO mice, muscle force measurement, histopathology, domain deletion analysis Human molecular genetics High 28934386
2017 In muscles from XLMTM patients, MTM1 mutations cause significant decrease in ryanodine receptor 1 (RyR1) expression, decrease in muscle-specific microRNAs, and up-regulation of histone deacetylase-4 (HDAC4); however, at the myotube level MTM1 mutations do not dramatically affect RyR1-mediated calcium homeostasis, indicating these molecular changes are secondary consequences in mature muscle rather than primary defects. Patient muscle biopsy analysis, patient-derived myotube calcium imaging, immunoblotting for RyR1/HDAC4, microRNA quantification Human molecular genetics Medium 28007904
2022 Disrupted T-tubular network in MTM1-deficient skeletal muscle fibers is the primary cause of asynchronous and severely impaired SR calcium release; mathematical modeling of T-tubule propagation defects reproduces all features of measured calcium release abnormalities, while Ca2+-induced calcium release from RyRs provides secondary support. Confocal calcium transient recordings in MTM1-deficient mouse muscle fibers, mathematical modeling of T-tubule depolarization propagation The Journal of physiology Medium 36408764
2023 Loss of MTM1 in zebrafish causes liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters; MTM1 localizes to Rab11-positive recycling endosomes in hepatocytes and associates with canalicular transport proteins; hepatocyte-specific re-expression of Mtm1 rescues the cholestatic phenotype; dynasore (a dynamin-2 inhibitor) partially restores bile flow and transporter localization. Zebrafish mtm1 loss-of-function model, reporter-tagged Mtm1 zebrafish line, co-localization with Rab11 and canalicular transporters, hepatocyte-specific rescue by re-expression, chemical screen with dynasore The Journal of clinical investigation High 37490339
2023 AAV-mediated MTM1 overexpression prevents and reverts BIN1-related centronuclear myopathy in Bin1mck-/- mice; the lipid phosphatase activity of MTM1 is essential for rescue of muscle atrophy and myofiber hypotrophy but dispensable for rescue of myofiber disorganization including organelle mis-position and T-tubule defects; rescue of T-tubule organization correlates with normalization of dysferlin and caveolin levels. AAV-MTM1 injection (systemic early and intramuscular late) in Bin1mck-/- mouse model, phosphatase-dead MTM1 mutant rescue experiment, histopathology, T-tubule imaging, immunoblotting for dysferlin and caveolin Brain : a journal of neurology High 37490306
2024 MTM1 is the main enzyme responsible for producing phosphatidylinositol 5-phosphate (PI5P) in muscle cells; this PI5P fuels PI5P 4-kinase α to generate a functional pool of PI(4,5)P2 that concentrates in podosome-like protrusions (PLPs) containing Tks5, Dynamin-2, and Myomaker, which drive myoblast fusion. Lipid mass spectrometry in MTM1-depleted myoblasts, PI5P and PI(4,5)P2 quantification, live imaging of PLP formation, co-localization of MTM1 products with PLP markers, myoblast fusion assays Proceedings of the National Academy of Sciences of the United States of America High 38805272
2025 MTM1 dephosphorylates a pool of PI3P on EEA1-positive early endosomes in skeletal muscle cells; loss of MTM1 causes PI3P accumulation on these endosomes and impairs Rab4-positive recycling vesicle biogenesis; depletion of class II PI3-kinase beta (PI3KC2β) in Mtm1-KO cells normalizes PI3P levels on EEA1-positive endosomes and restores Rab4-positive vesicle biogenesis. Mtm1-KO skeletal muscle cell line, PI3P localization by immunofluorescence on endosomal compartments, Rab4 vesicle biogenesis assay, PI3KC2β depletion rescue experiments Journal of lipid research High 39952567
2011 The human MTM1 p.R69C mutation modeled in mice causes exon 4 skipping in most mRNA transcripts (rather than a simple missense change), leading to premature termination and very low myotubularin protein; residual full-length transcript provides enough myotubularin activity to maintain near-normal PI3P levels and account for a milder phenotype compared to complete KO mice. Knock-in mouse model, RT-PCR/mRNA analysis, Western blot for myotubularin protein, PI3P level measurement in muscle Human molecular genetics High 22068590

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 MTM1 mutations in X-linked myotubular myopathy. Human mutation 161 10790201
2003 Manganese activation of superoxide dismutase 2 in Saccharomyces cerevisiae requires MTM1, a member of the mitochondrial carrier family. Proceedings of the National Academy of Sciences of the United States of America 115 12890866
1997 Mutations in the MTM1 gene implicated in X-linked myotubular myopathy. ENMC International Consortium on Myotubular Myopathy. European Neuro-Muscular Center. Human molecular genetics 107 9305655
2010 MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proceedings of the National Academy of Sciences of the United States of America 100 20682747
2008 "Necklace" fibers, a new histological marker of late-onset MTM1-related centronuclear myopathy. Acta neuropathologica 94 19084976
1995 Myotubular myopathy in a girl with a deletion at Xq27-q28 and unbalanced X inactivation assigns the MTM1 gene to a 600-kb region. American journal of human genetics 72 7726166
2013 Lack of myotubularin (MTM1) leads to muscle hypotrophy through unbalanced regulation of the autophagy and ubiquitin-proteasome pathways. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 54 23695157
2017 Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues. Acta neuropathologica 52 28685322
2011 Modeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype. Human molecular genetics 52 22068590
2009 Caenorhabditis elegans myotubularin MTM-1 negatively regulates the engulfment of apoptotic cells. PLoS genetics 52 19816564
2018 The MTM1-UBQLN2-HSP complex mediates degradation of misfolded intermediate filaments in skeletal muscle. Nature cell biology 40 29358706
1999 Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X-linked myotubular myopathy patients. Neuromuscular disorders : NMD 40 10063835
1999 Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy. Human mutation 39 10502779
2007 Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy. Neuromuscular disorders : NMD 37 17537630
2005 Characterization of MTM1 mutations in 31 Japanese families with myotubular myopathy, including a patient carrying 240 kb deletion in Xq28 without male hypogenitalism. Neuromuscular disorders : NMD 36 15725586
2015 X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene. Skeletal muscle 32 25664165
2003 X-linked myotubular myopathy in a female infant caused by a new MTM1 gene mutation. Neurology 32 12707446
2014 Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice. The American journal of pathology 30 24726641
1998 Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene. Human mutation 30 9450905
2011 The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5-CED-12 in C. elegans. Development (Cambridge, England) 29 21490059
1999 The novel contiguous gene syndrome of myotubular myopathy (MTM1), male hypogenitalism and deletion in Xq28:report of the first familial case. Cytogenetics and cell genetics 28 10449925
2017 Cellular, biochemical and molecular changes in muscles from patients with X-linked myotubular myopathy due to MTM1 mutations. Human molecular genetics 26 28007904
2016 Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers. Neuromuscular disorders : NMD 26 27017278
2012 Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database. European journal of human genetics : EJHG 24 22968136
2019 Adult MTM1-related myopathy carriers: Classification based on deep phenotyping. Neurology 23 31541013
2002 Rapid scanning of myotubularin (MTM1) gene by denaturing high-performance liquid chromatography (DHPLC). Neuromuscular disorders : NMD 22 12031625
1998 Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy. European journal of human genetics : EJHG 22 9781038
1998 Genomic organization of a 225-kb region in Xq28 containing the gene for X-linked myotubular myopathy (MTM1) and a related gene (MTMR1). Genomics 22 9828128
2017 Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy. Human molecular genetics 21 28934386
1994 X linked myotubular myopathy (MTM1) maps between DXS304 and DXS305, closely linked to the DXS455 VNTR and a new, highly informative microsatellite marker (DXS1684). Journal of medical genetics 20 7891372
2022 Circ_FURIN knockdown assuages Testosterone-induced human ovarian granulosa-like tumor cell disorders by sponging miR-423-5p to reduce MTM1 expression in polycystic ovary syndrome. Reproductive biology and endocrinology : RB&E 19 35177076
2006 Extreme phenotypic variability in a German family with X-linked myotubular myopathy associated with E404K mutation in MTM1. Neuromuscular disorders : NMD 19 17005396
2013 Site-specific Mtm1 mutagenesis by an AAV-Cre vector reveals that myotubularin is essential in adult muscle. Human molecular genetics 18 23390130
1998 MTM1 gene mutations in Japanese patients with the severe infantile form of myotubular myopathy. Neuromuscular disorders : NMD 17 9829274
2023 Loss of Mtm1 causes cholestatic liver disease in a model of X-linked myotubular myopathy. The Journal of clinical investigation 16 37490339
2011 Myopathy in a woman and her daughter associated with a novel splice site MTM1 mutation. Neuromuscular disorders : NMD 14 22101172
2023 MTM1 overexpression prevents and reverts BIN1-related centronuclear myopathy. Brain : a journal of neurology 13 37490306
2020 Pathogenic deep intronic MTM1 variant activates a pseudo-exon encoding a nonsense codon resulting in severe X-linked myotubular myopathy. European journal of human genetics : EJHG 12 32862205
2024 MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion. Proceedings of the National Academy of Sciences of the United States of America 10 38805272
2022 Circ_MTM1 knockdown inhibits the progression of HBV-related liver fibrosis via regulating IL7R expression through targeting miR-122-5p. American journal of translational research 10 35559382
2011 X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10. Neuromuscular disorders : NMD 9 22153990
2022 X-linked myotubular myopathy associated with an MTM1 variant in a Maine coon cat. Journal of veterinary internal medicine 8 35962713
2021 MTM1 plays an important role in the regulation of zinc tolerance in Saccharomyces cerevisiae. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 8 33872833
2018 Non-compaction cardiomyopathy and early respiratory failure in an adult symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation. Neuromuscular disorders : NMD 8 30241883
2018 Whole exome sequencing discloses a pathogenic MTM1 gene mutation and ends the diagnostic odyssey in an older woman with a progressive and seemingly sporadic myopathy: Case report and literature review of MTM1 manifesting female carriers. Neuromuscular disorders : NMD 7 29567349
2015 Mutation spectrum of the MTM1 gene in XLMTM patients: 10 years of experience in prenatal and postnatal diagnosis. Clinical genetics 7 26338224
2011 X-linked myotubular myopathy in a family with two infant siblings: a case with MTM1 mutation. Yonsei medical journal 7 21488203
2020 A Deep Intronic Variant Activates a Pseudoexon in the MTM1 Gene in a Family with X-Linked Myotubular Myopathy. Molecular syndromology 6 33505229
2013 X-linked recessive myotubular myopathy with MTM1 mutations. Korean journal of pediatrics 6 23559977
2012 Large duplication in MTM1 associated with myotubular myopathy. Neuromuscular disorders : NMD 6 23273872
1998 A novel mutation in exon b (R259C) of the MTM1 gene is associated with a mild myotubular myopathy. Mutation in brief no. 125. Online. Human mutation 6 10215413
2020 A mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels. Neuromuscular disorders : NMD 5 32417001
2019 Three novel MTM1 pathogenic variants identified in Japanese patients with X-linked myotubular myopathy. Molecular genetics & genomic medicine 5 30884204
2018 Using exome sequencing to decipher family history in a healthy individual: Comparison of pathogenic and population MTM1 variants. Molecular genetics & genomic medicine 5 30047259
2020 X-linked myotubular myopathy mimics hereditary spastic paraplegia in two female manifesting carriers of pathogenic MTM1 variant. European journal of medical genetics 4 32805447
2012 Myotubular myopathy caused by multiple abnormal splicing variants in the MTM1 RNA in a patient with a mild phenotype. European journal of human genetics : EJHG 4 22258523
2025 PI3KC2β depletion rescues endosomal trafficking defects in Mtm1 knockout skeletal muscle cells. Journal of lipid research 3 39952567
2022 MTM1 displays a new function in the regulation of nickel resistance in Saccharomyces cerevisiae. Metallomics : integrated biometal science 3 36138538
2013 Two Cases of X-Linked Myotubular Myopathy with Novel MTM1 Mutations. Journal of clinical neurology (Seoul, Korea) 3 23346162
2008 X-linked myotubular myopathy with a novel MTM1 mutation in a Taiwanese child. Journal of the Formosan Medical Association = Taiwan yi zhi 3 19129059
2024 [Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2 38946363
2023 Whole exome sequencing discloses a pathogenic MTM1 gene mutation in a continuous polyhydramnios family in China: Case report and literature review. European journal of obstetrics, gynecology, and reproductive biology 2 37813004
2022 Disrupted T-tubular network accounts for asynchronous calcium release in MTM1-deficient skeletal muscle. The Journal of physiology 2 36408764
2011 Congenital myotubular myopathy with a novel MTM1 gene mutation in a premature infant presenting with ventilator dependency and intrahepatic cholestasis. Journal of child neurology 2 21881007
2006 Floppy infant caused by MTM1 mutation: a first genetically-confirmed X-linked myotubular myopathy patient in Thailand. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 2 16583589
2023 Generation of an MTM1-mutant iPSC line (CRICKi008-A) from an individual with X-linked myotubular myopathy (XLMTM). Stem cell research 1 36989620
2022 Novel Splicing Mutation in MTM1 Leading to Two Abnormal Transcripts Causes Severe Myotubular Myopathy. International journal of molecular sciences 1 36142184
2011 Identification of a mutation in the MTM1 gene, associated with X-linked myotubular myopathy, in a Greek family. Hippokratia 1 22435031
1996 Detection of a new polymorphism in the plasma-membrane Ca2+ ATPase isoform-3 gene and its exclusion as a candidate for X-linked myotubular myopathy (MTM1). Human genetics 1 8931700
2026 Identification of a Novel MTM1 Mutation Associated with X-Linked Myotubular Myopathy: Clinical and Molecular Insights for Prenatal Diagnosis. International journal of women's health 0 41873413
2026 Unexpected perinatal death caused by an occult MTM1 mutation: a case report. Frontiers in medicine 0 41952898
2025 [Clinical and genetic features of 5 neonates with centronuclear myopathy caused by MTM1 gene variation]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 40962517
2023 X-Linked Myotubular Myopathy in a Female Patient with a Pathogenic Variant in the MTM1 Gene. International journal of molecular sciences 0 37176116
2021 Erratum: Identification of a mutation in the MTM1 gene, associated with X-linked myotubular myopathy, in a Greek family. Hippokratia 0 36157684
2010 [Screen in Saccharomyces cerevisiae for transposon insertion sites able to rescue phenotype of MTM1 deletion mutant using mTn-lacZ/LEU2 transposon library]. Wei sheng wu xue bao = Acta microbiologica Sinica 0 20344951

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