MTM1

myotubularin 1, the group of Myotubularins|Phosphoinositide phosphatases

Basic information

Region (hg38): X:150568416-150673143

Links

ENSG00000171100 ∙ NCBI:4534 ∙ OMIM:300415 ∙ HGNC:7448 ∙ Uniprot:Q13496 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked myotubular myopathy (Definitive), mode of inheritance: XL
• X-linked myotubular myopathy (Definitive), mode of inheritance: XLR
• 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: CGD

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 ClinVar and linked to the MTM1 gene.

• Severe X-linked myotubular myopathy (538 variants)
• not provided (126 variants)
• not specified (31 variants)
• Inborn genetic diseases (13 variants)
• MTM1-related condition (2 variants)
• See cases (2 variants)
• 13 conditions (1 variants)
• Neurodevelopmental disorder (1 variants)
• Generalized hypotonia (1 variants)
• Autosomal dominant centronuclear myopathy (1 variants)
• Centronuclear myopathy (1 variants)
• Spastic paraplegia (1 variants)
• MTM1-related disorder (1 variants)
• Qualitative or quantitative defects of myotubularin (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	116	18	135
missense	29	25	95	8	14	171
nonsense	39	14				53
start loss	3					3
frameshift	48	15				63
inframe indel	3	1	1			5
splice donor/acceptor (+/-2bp)	33	7			1	41
splice region	2	3	9	23	4	41
non coding	2	2	2	62	23	91
Total	157	64	99	186	56

Highest pathogenic variant AF is 0.00000893

Variants in MTM1

This is a list of pathogenic ClinVar variants found in the MTM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-150568509-C-T			Likely benign (Feb 25, 2022)
X-150568596-CAGAGGGGGCGGAGCAGGGCCCGGCAGCCGAGCAGCCTGGCAACGGCGGTGGCGCCCGGAGCCCGAG-C		Severe X-linked myotubular myopathy	Pathogenic (-)
X-150568625-G-C		not specified	Likely benign (Aug 10, 2016)
X-150568649-G-T			Likely benign (May 10, 2018)
X-150568713-C-T			Likely benign (Dec 01, 2021)
X-150592277-A-G			Benign (Jun 26, 2018)
X-150592357-C-T			Likely benign (Feb 25, 2020)
X-150592453-G-G			Benign (Jun 16, 2018)
X-150592616-T-C		Severe X-linked myotubular myopathy	Pathogenic (Jun 30, 2022)
X-150592616-T-G		Severe X-linked myotubular myopathy	Pathogenic (Feb 08, 2013)
X-150592617-G-A		Severe X-linked myotubular myopathy	Pathogenic (Feb 08, 2013)
X-150592619-C-T		Severe X-linked myotubular myopathy	Uncertain significance (Dec 14, 2018)
X-150592620-T-C		Severe X-linked myotubular myopathy	Likely benign (Nov 11, 2022)
X-150592620-T-G		Severe X-linked myotubular myopathy	Likely benign (Dec 10, 2023)
X-150592629-A-C		Severe X-linked myotubular myopathy	Likely benign (Oct 11, 2019)
X-150592630-A-G		Severe X-linked myotubular myopathy	Likely benign (Jan 30, 2024)
X-150592631-CT-C			Pathogenic (Jul 14, 2016)
X-150592632-T-A		Severe X-linked myotubular myopathy	Likely benign (Jan 22, 2024)
X-150592635-T-G		Severe X-linked myotubular myopathy	Likely benign (Dec 18, 2021)
X-150592641-T-C		Severe X-linked myotubular myopathy	Likely benign (Jun 14, 2023)
X-150592641-T-G		Severe X-linked myotubular myopathy	Pathogenic (Aug 17, 2023)
X-150592646-C-T		Severe X-linked myotubular myopathy	Uncertain significance (Jun 20, 2022)
X-150592652-C-T		Severe X-linked myotubular myopathy • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 18, 2023)
X-150592663-G-T			Pathogenic (Feb 18, 2016)
X-150592665-G-A		Severe X-linked myotubular myopathy	Likely benign (Jan 16, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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