MTM1

Chr X

myotubularin 1

Also known as: CNM, CNMX, MTMX, XLMTM

NCBI Gene: 4534ENSG00000171100UniProt: Q13496

This gene encodes a dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. It is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtMyopathy, centronuclear, X-linked
498
ClinVar variants
115
Pathogenic / LP
1.00
pLI score· haploinsufficient
4
Active trials
Clinical Summary— MTM1
🧬
Gene-Disease Validity (ClinGen)
X-linked myotubular myopathy · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
115 Pathogenic / Likely Pathogenic· 143 VUS of 498 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.18LOEUF
pLI 1.000
Z-score 4.63
OE 0.04 (0.01–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.39Z-score
OE missense 0.57 (0.49–0.65)
138 obs / 243.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.49–0.65)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.77
0≤1.21.6
LoF obs/exp: 1 / 26.9Missense obs/exp: 138 / 243.1Syn Z: 1.65

ClinVar Variant Classifications

498 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic76
Likely Pathogenic39
VUS143
Likely Benign198
Benign31
Conflicting11
76
Pathogenic
39
Likely Pathogenic
143
VUS
198
Likely Benign
31
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
2
52
0
76
Likely Pathogenic
10
11
18
0
39
VUS
0
118
18
7
143
Likely Benign
0
8
86
104
198
Benign
0
5
17
9
31
Conflicting
—11
Total32144191120498

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MTM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MTM1-related myotubular myopathy

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — MTM1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
X-linked myotubular myopathy.
Lawlor MW et al.·Neuromuscul Disord
2021Review
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.
Gómez-Oca R et al.·Int J Mol Sci
2021Review
Centronuclear (myotubular) myopathy.
Jungbluth H et al.·Orphanet J Rare Dis
2008Review
Congenital myopathies: pathophysiological mechanisms and promising therapies.
Zhang H et al.·J Transl Med
2024Review
Loss of Mtm1 causes cholestatic liver disease in a model of X-linked myotubular myopathy.
Karolczak S et al.·J Clin Invest
2023Functional
MTM1 overexpression prevents and reverts BIN1-related centronuclear myopathy.
Giraud Q et al.·Brain
2023
PI3KC2β depletion rescues endosomal trafficking defects in Mtm1 knockout skeletal muscle cells.
Mansat M et al.·J Lipid Res
2025
MTM1 mutations in X-linked myotubular myopathy.
Laporte J et al.·Hum Mutat
2000Review
Integrative Multi-Omics and Network Analyses Reveal Pathogenic and Protective Pathways in Centronuclear Myopathies.
Simon A et al.·Int J Mol Sci
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
X-Linked Myotubular Myopathy

A Study of AT132 in Young Children With X-Linked Myotubular Myopathy (XLMTM)

ACTIVE NOT RECRUITING
NCT03199469Phase PHASE2, PHASE3Astellas Gene TherapiesStarted 2017-08-02
Resamirigene bilparvovec
X-Linked Myotubular Myopathy

Study of ASP2957 in Male Participants With X-linked Myotubular Myopathy Who Need Ventilators

RECRUITING
NCT07052929Phase PHASE1, PHASE2Astellas Gene TherapiesStarted 2025-12-15
ASP2957MethylprednisolonePrednisolone
X-Linked Myotubular Myopathy

A Study to Check Liver Health in Boys With XLMTM, a Serious Genetic Muscle Condition

RECRUITING
NCT06581146Astellas Gene TherapiesStarted 2025-05-19
No Intervention
Myotubular MyopathyMyotubular Myopathy 1Myotubular (Centronuclear) Myopathy

Myotubular and Centronuclear Myopathy Patient Registry

RECRUITING
NCT04064307Newcastle-upon-Tyne Hospitals NHS TrustStarted 2013-03-26

External Resources

Links to major genomics databases and tools