MTMR2

Chr 11AR

myotubularin related protein 2

Also known as: CMT4B, CMT4B1

The encoded protein is a phosphoinositide lipid phosphatase that dephosphorylates phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate. Mutations cause Charcot-Marie-Tooth disease type 4B1, an autosomal recessive demyelinating neuropathy. The pathogenic mechanism involves dominant-negative effects of mutant protein.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.651 OMIM phenotype
Clinical SummaryMTMR2
🧬
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 OE0.44 (0.300.65)
00.351.4
Missense OE0.81 (0.730.90)
00.61.4
Synonymous OE0.76
01.21.6
LoF obs/exp: 18 / 40.8Missense obs/exp: 272 / 334.7Syn Z: 2.02
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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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