MTM1 Gene: Myotubularin 1 - Function, Mutations, and Associated Diseases
Comprehensive biomedical resource on MTM1, including gene structure, expression, mutations, and clinical significance in X-linked myotubular myopathy.
Gene Information Card
| Symbol | MTM1 |
|---|---|
| Full Name | Myotubularin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 4534 ncbi.nlm.nih.gov/gene/4534 |
| Ensembl ID | ENSG00000132773 |
| UniProt ID | Q13496 |
| OMIM ID | 300415 |
| HGNC ID | 7448 |
| Aliases | CNM, MTMX, XLMTM |
Description
The MTM1 gene encodes myotubularin 1, a lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). It is critical for endosomal trafficking, membrane dynamics, and muscle cell differentiation. Mutations in MTM1 cause X-linked myotubular myopathy (XLMTM), a severe congenital muscle disorder. MTM1 is also implicated in other myopathies and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked myotubular myopathy (XLMTM) | Loss-of-function mutations lead to reduced PI3P dephosphorylation, disrupting endosomal trafficking and muscle cell maturation, causing severe hypotonia and respiratory failure. | ClinVar, OMIM (300415) |
| Centronuclear myopathy (CNM) | MTM1 mutations, including missense variants, can cause autosomal recessive or dominant forms of CNM, with similar pathogenic mechanisms as XLMTM. | ClinVar, OMIM |
| Hepatocellular carcinoma (HCC) | MTM1 expression is downregulated in HCC, leading to increased PI3P levels and altered autophagy, promoting tumor progression. | COSMIC, PubMed (e.g., PMID 23455924) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.4 | Medium |
| Heart | 8.9 | Low |
| Liver | 5.2 | Low |
| Brain | 4.1 | Low |
| Testis | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RH-30 (muscle) | 15.2 | High expression; relevant for muscle studies |
| HepG2 (liver) | 6.3 | Moderate; used in cancer studies |
| A549 (lung) | 2.1 | Low |
| MCF7 (breast) | 1.8 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1261C>T (p.Arg421Ter) | Nonsense | ~10% of XLMTM cases | Premature stop codon, loss of function |
| c.205C>T (p.Arg69Cys) | Missense | Reported in CNM | Impairs catalytic activity |
| c.1441G>A (p.Gly481Arg) | Missense | Rare | Disrupts protein stability |
| c.1261+1G>A | Splice site | Reported | Aberrant splicing, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most MTM1 mutations are loss-of-function, leading to reduced or absent myotubularin activity, causing XLMTM.
Gain of Function (GOF)
No evidence for gain-of-function mutations in MTM1.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects in autosomal dominant CNM, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-3-phosphatase activity | • phosphatidylinositol-3 |
| • 5-bisphosphate 3-phosphatase activity | • protein tyrosine phosphatase activity |
| • endosome membrane | • cytosol |
| • nucleus | • signal transduction |
| • endosomal transport | • muscle cell differentiation |
Pathways
• Phosphatidylinositol phosphate metabolism
• Endosomal trafficking
• Autophagy regulation
Protein Summary
Myotubularin 1 is a 603-amino acid protein with a catalytic protein tyrosine phosphatase (PTP) domain and a GRAM domain that binds phosphoinositides. It primarily dephosphorylates PI3P and PI(3,5)P2, regulating endosomal membrane dynamics. The protein is ubiquitously expressed but most critical in skeletal muscle, where it controls myotube formation and T-tubule organization. Mutations cause myotubular myopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MTM1 Knockout HEK293 Cell Line | EDJ-KQ1661 | Human | 4534 | Details Get a Quote |
| CMTM1 Knockout HEK293 Cell Line | EDJ-KQ7425 | Human | 113540 | Details Get a Quote |
| MTM1 Knockout A-549 Cell Line | EDJ-KQ21422 | Human | 4534 | Details Get a Quote |
| MTM1 Knockout HCT 116 Cell Line | EDJ-KQ21423 | Human | 4534 | Details Get a Quote |
| MTM1 Knockout HeLa Cell Line | EDJ-KQ21424 | Human | 4534 | Details Get a Quote |
| CMTM1 Knockout A-549 Cell Line | EDJ-KQ32619 | Human | 113540 | Details Get a Quote |
| CMTM1 Knockout HCT 116 Cell Line | EDJ-KQ32620 | Human | 113540 | Details Get a Quote |
| CMTM1 Knockout HeLa Cell Line | EDJ-KQ32621 | Human | 113540 | Details Get a Quote |
| CKLF-CMTM1 Knockout HEK293 Cell Line | EDJ-KQ52498 | Human | 100529251 | Details Get a Quote |
| CKLF-CMTM1 Knockout HeLa Cell Line | EDJ-KQ60961 | Human | 100529251 | Details Get a Quote |
| CKLF-CMTM1 Knockout A-549 Cell Line | EDJ-KQ69436 | Human | 100529251 | Details Get a Quote |
| CKLF-CMTM1 Knockout HCT 116 Cell Line | EDJ-KQ77787 | Human | 100529251 | Details Get a Quote |
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