MTMR2

Chr 11AR

myotubularin related protein 2

Also known as: CMT4B, CMT4B1

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]

OMIMResearchGenerating clinical summary…
DNmechanismARLOEUF 0.651 OMIM phenotype
Clinical SummaryMTMR2
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.65LOEUF
pLI 0.000
Z-score 3.31
OE 0.44 (0.300.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.22Z-score
OE missense 0.81 (0.730.90)
272 obs / 334.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.44 (0.300.65)
00.351.4
Missense OE?0.81 (0.730.90)
00.61.4
Synonymous OE?0.76
01.21.6
LoF obs/exp: 18 / 40.8Missense obs/exp: 272 / 334.7Syn Z: 2.02

This gene — mechanism propensity

DN
0.7036th %ile
GOF
0.5955th %ile
LOF
0.2774th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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