MTM1
myotubularin 1, the group of Myotubularins|Phosphoinositide phosphatases
Basic information
Region (hg38): X:150568417-150673143
Links
Phenotypes
GenCC
Source:
- X-linked myotubular myopathy (Definitive), mode of inheritance: XL
- X-linked myotubular myopathy (Moderate), mode of inheritance: XL
- X-linked myotubular myopathy (Strong), mode of inheritance: XL
- X-linked myotubular myopathy (Definitive), mode of inheritance: XL
- X-linked myotubular myopathy (Supportive), mode of inheritance: XL
- X-linked myotubular myopathy (Definitive), mode of inheritance: XL
- X-linked myotubular myopathy (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Myopathy, centronuclear, X-linked | XL | Hematologic | Among other findings affecting multiple organ systems, individuals may demonstrate a vitamin-K respondent bleeding diathesis, and surveillance and treatment may be beneficial | Gastrointestinal; Hematologic; Musculoskeletal; Renal | 5816884; 8640223; 9285787; 9169146; 9305655; 10726846; 9450905; 9931531; 10502779; 10323249; 10714588; 10790201; 11552027; 12707446; 15883335; 15690409; 19197364; 20434914; 20500434; 21881007; 22101172; 22153990; 22258523; 22264517; 22520358 |
| Increased risk of findings including subdural hemorrhage, subdural hygromas, and cephalohematomas has been reported |
ClinVar
This is a list of variants' phenotypes submitted to
- Severe_X-linked_myotubular_myopathy (676 variants)
- not_provided (137 variants)
- Inborn_genetic_diseases (44 variants)
- not_specified (32 variants)
- Centronuclear_myopathy (20 variants)
- MTM1-related_disorder (10 variants)
- Neurodevelopmental_disorder (1 variants)
- Generalized_hypotonia (1 variants)
- Autosomal_dominant_centronuclear_myopathy (1 variants)
- Spastic_paraplegia (1 variants)
- Qualitative_or_quantitative_defects_of_myotubularin (1 variants)
- See_cases (1 variants)
- Congenital_myopathy_with_fiber_type_disproportion (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000252.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 147 | 20 | 176 | |||
| missense | 30 | 47 | 146 | 24 | 12 | 259 |
| nonsense | 44 | 17 | 61 | |||
| start loss | 3 | 3 | ||||
| frameshift | 61 | 21 | 83 | |||
| splice donor/acceptor (+/-2bp) | 34 | 44 | ||||
| Total | 172 | 95 | 154 | 172 | 33 |
Highest pathogenic variant AF is 0.00000184468
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MTM1 | protein_coding | protein_coding | ENST00000370396 | 14 | 104727 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000395 | 125421 | 0 | 1 | 125422 | 0.00000399 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.40 | 138 | 243 | 0.568 | 0.0000194 | 3978 |
| Missense in Polyphen | 43 | 113.62 | 0.37846 | 1872 | ||
| Synonymous | 1.65 | 66 | 85.5 | 0.772 | 0.00000702 | 1110 |
| Loss of Function | 4.63 | 1 | 26.9 | 0.0372 | 0.00000235 | 395 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000122 | 0.00000882 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine- containing peptides. Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome. Plays a role in vacuolar formation and morphology. Regulates desmin intermediate filament assembly and architecture. Plays a role in mitochondrial morphology and positioning. Required for skeletal muscle maintenance but not for myogenesis. {ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:14722070, ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:9537414}.;
- Disease
- DISEASE: Myopathy, centronuclear, X-linked (CNMX) [MIM:310400]: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. {ECO:0000269|PubMed:10063835, ECO:0000269|PubMed:10466421, ECO:0000269|PubMed:10502779, ECO:0000269|PubMed:10790201, ECO:0000269|PubMed:11793470, ECO:0000269|PubMed:12031625, ECO:0000269|PubMed:12522554, ECO:0000269|PubMed:12859411, ECO:0000269|PubMed:17005396, ECO:0000269|PubMed:19129059, ECO:0000269|PubMed:9285787, ECO:0000269|PubMed:9305655, ECO:0000269|PubMed:9829274}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Metabolism of lipids;Metabolism;Synthesis of PIPs at the early endosome membrane;Synthesis of PIPs at the plasma membrane;Synthesis of PIPs at the late endosome membrane;PI Metabolism;Phospholipid metabolism
(Consensus)
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- loftool
- 0.0493
- rvis_EVS
- -0.52
- rvis_percentile_EVS
- 21.2
Haploinsufficiency Scores
- pHI
- 0.317
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.511
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.686
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mtm1
- Phenotype
- skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- mtm1
- Affected structure
- skeletal muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased functionality
Gene ontology
- Biological process
- protein dephosphorylation;phosphatidylinositol biosynthetic process;endosome to lysosome transport;protein transport;negative regulation of TOR signaling;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;peptidyl-tyrosine dephosphorylation;regulation of vacuole organization;intermediate filament organization;muscle cell cellular homeostasis;phosphatidylinositol dephosphorylation;mitochondrion distribution;positive regulation of skeletal muscle tissue growth;negative regulation of protein kinase B signaling;mitochondrion morphogenesis;negative regulation of autophagosome assembly
- Cellular component
- ruffle;cytoplasm;late endosome;cytosol;plasma membrane;filopodium;I band
- Molecular function
- phosphatidylinositol-3-phosphatase activity;phosphoprotein phosphatase activity;protein tyrosine phosphatase activity;protein binding;intermediate filament binding;phosphatidylinositol binding;phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity