MTMR2

myotubularin related protein 2, the group of Myotubularins|Phosphoinositide phosphatases

Basic information

Region (hg38): 11:95821765-95925315

Previous symbols: [ "CMT4B" ]

Links

ENSG00000087053 ∙ NCBI:8898 ∙ OMIM:603557 ∙ HGNC:7450 ∙ Uniprot:Q13614 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease type 4B1 (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4B1 (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4B1 (Supportive), mode of inheritance: AR
• demyelinating hereditary motor and sensory neuropathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, type 4B1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	10802647

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTMR2 gene.

• Charcot-Marie-Tooth disease type 4 (361 variants)
• Mosaic variegated aneuploidy syndrome 2 (189 variants)
• not provided (102 variants)
• Charcot-Marie-Tooth disease type 4B1 (87 variants)
• Inborn genetic diseases (87 variants)
• Charcot-Marie-Tooth disease (41 variants)
• not specified (27 variants)
• Mosaic variegated aneuploidy syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTMR2 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			2	67	4	73
missense		3	170	4	3	180
nonsense	11	1	3			15
start loss						0
frameshift	12	4	3			19
inframe indel			4			4
splice donor/acceptor (+/-2bp)	2	3				5
splice region			18	21	2	41
non coding	4	1	162	129	49	345
Total	29	12	344	200	56

Highest pathogenic variant AF is 0.0000197

Variants in MTMR2

This is a list of pathogenic ClinVar variants found in the MTMR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-95821852-A-C		Mosaic variegated aneuploidy syndrome 2	Likely benign (Dec 29, 2023)
11-95821867-C-T		Mosaic variegated aneuploidy syndrome 2	Likely benign (Oct 09, 2020)
11-95821872-T-G		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Nov 13, 2018)
11-95821875-A-G		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Jan 22, 2020)
11-95821878-C-A		Inborn genetic diseases • Mosaic variegated aneuploidy syndrome 2	Uncertain significance (May 01, 2022)
11-95821882-T-A		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jun 01, 2020)
11-95821889-A-G		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Dec 29, 2022)
11-95821894-T-C		Mosaic variegated aneuploidy syndrome 2	Likely benign (Apr 06, 2022)
11-95821894-T-G		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Sep 08, 2023)
11-95821894-TA-T		Mosaic variegated aneuploidy syndrome	Pathogenic (-)
11-95821900-T-C		Mosaic variegated aneuploidy syndrome 2	Likely benign (Nov 29, 2022)
11-95821902-T-C		Inborn genetic diseases	Likely benign (Jun 07, 2022)
11-95821903-C-A		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jan 08, 2024)
11-95821913-A-G		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Mar 01, 2020)
11-95821917-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Dec 03, 2019)
11-95821922-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Jan 16, 2024)
11-95821923-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Jan 15, 2024)
11-95821924-G-A		Mosaic variegated aneuploidy syndrome 2	Benign (Feb 01, 2024)
11-95821924-G-C		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jul 10, 2023)
11-95821926-G-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Dec 23, 2021)
11-95821934-A-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Mar 11, 2022)
11-95821935-A-G		Mosaic variegated aneuploidy syndrome 2 • CEP57-related disorder	Conflicting classifications of pathogenicity (Jan 03, 2024)
11-95821938-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Aug 27, 2021)
11-95821943-A-C		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jun 13, 2022)
11-95821949-A-T		Mosaic variegated aneuploidy syndrome 2	Pathogenic (Aug 04, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTMR2	protein_coding	protein_coding	ENST00000346299	15	92434

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.04e-7	1.00	125688	0	58	125746	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	272	335	0.813	0.0000171	4175
Missense in Polyphen		45	86.054	0.52293		1108
Synonymous	2.02	91	119	0.764	0.00000576	1225
Loss of Function	3.31	18	40.8	0.441	0.00000274	438

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000539	0.000539
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.0000944	0.0000924
European (Non-Finnish)	0.000186	0.000185
Middle Eastern	0.000381	0.000381
South Asian	0.000425	0.000425
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate. {ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:21372139}.
• Disease: DISEASE: Charcot-Marie-Tooth disease 4B1 (CMT4B1) [MIM:601382]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. {ECO:0000269|PubMed:10802647, ECO:0000269|PubMed:12398840}. 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;Nicotinate Nicotinamide metabolism;Synthesis of PIPs at the ER membrane;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: 0.218

Intolerance Scores

• loftool: 0.101
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.54

Haploinsufficiency Scores

• pHI: 0.130
• hipred: N
• hipred_score: 0.488
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.957

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mtmr2
• Phenotype: growth/size/body region phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system phenotype; normal 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of receptor internalization;protein dephosphorylation;phosphatidylinositol biosynthetic process;negative regulation of myelination;myelin assembly;peptidyl-tyrosine dephosphorylation;negative regulation of endocytosis;inositol phosphate dephosphorylation;phosphatidylinositol dephosphorylation;neuron development;protein tetramerization;regulation of phosphatidylinositol dephosphorylation;negative regulation of excitatory postsynaptic potential;dendritic spine maintenance;positive regulation of early endosome to late endosome transport;negative regulation of receptor catabolic process
• Cellular component: nucleus;cytoplasm;vacuolar membrane;cytosol;synaptic vesicle;postsynaptic density;axon;dendrite;early endosome membrane;dendritic spine;intracellular membrane-bounded organelle;extracellular exosome;synaptic membrane
• Molecular function: phosphatidylinositol-3-phosphatase activity;protein tyrosine phosphatase activity;protein binding;protein tyrosine/serine/threonine phosphatase activity;protein homodimerization activity;phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity