MTMR2

Chr 11AR

myotubularin related protein 2

Also known as: CMT4B, CMT4B1

NCBI Gene: 8898ENSG00000087053UniProt: Q13614

This gene is a member of the myotubularin family of phosphoinositide lipid phosphatases. The encoded protein possesses phosphatase activity towards phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 4B1MIM #601382
AR
579
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MTMR2
🧬
Gene-Disease Validity (ClinGen)
demyelinating hereditary motor and sensory neuropathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 257 VUS of 579 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.65LOEUF
pLI 0.000
Z-score 3.31
OE 0.44 (0.30–0.65)
Tolerant

Typical tolerance to LoF variation

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.
1.22Z-score
OE missense 0.81 (0.73–0.90)
272 obs / 334.7 exp
Tolerant

Mild missense constraint

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.0.44 (0.30–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.90)
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.0.76
0≤1.21.6
LoF obs/exp: 18 / 40.8Missense obs/exp: 272 / 334.7Syn Z: 2.02

ClinVar Variant Classifications

579 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic26
VUS257
Likely Benign182
Benign49
Conflicting20
45
Pathogenic
26
Likely Pathogenic
257
VUS
182
Likely Benign
49
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
30
0
45
Likely Pathogenic
15
3
8
0
26
VUS
9
183
61
4
257
Likely Benign
1
5
101
75
182
Benign
1
2
42
4
49
Conflicting
—20
Total4119324283579

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

View in ClinVar →

Protein Context — Lollipop Plot

MTMR2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, type 4B1

MIM #601382

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MTMR2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An integrative analysis reveals the prognostic value and potential functions of MTMR2 in hepatocellular carcinoma.
Yao Y et al.·Sci Rep
2023
MTMR2 promotes the progression of NK/T cell lymphoma by targeting JAK1.
Wang J et al.·Eur Rev Med Pharmacol Sci
2020
Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy.
Raess MA et al.·Hum Mol Genet
2017
MTMR2 promotes invasion and metastasis of gastric cancer via inactivating IFNγ/STAT1 signaling.
Jiang L et al.·J Exp Clin Cancer Res
2019
Current profile of Charcot-Marie-Tooth disease in Africa: A systematic review.
Yalcouyé A et al.·J Peripher Nerv Syst
2022Review
[Hereditary neuropathy: recent advance].
Nakagawa M·Rinsho Shinkeigaku
2008Review
Autosomal-recessive forms of demyelinating Charcot-Marie-Tooth disease.
Dubourg O et al.·Neuromolecular Med
2006Review
Novel MTMR2 mutation causing severe Charcot-Marie-Tooth type 4B1 disease: a case report.
Halperin D et al.·Neurogenetics
2020Case report
Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy.
Cook S et al.·Neuromuscul Disord
2023Functional
Differential phosphorylation of the phosphoinositide 3-phosphatase MTMR2 regulates its association with early endosomal subtypes.
Franklin NE et al.·J Cell Sci
2013
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools