MPZ
Chr 1ADARmyelin protein zero
Also known as: CMT1, CMT1B, CMT2I, CMT2J, CMT4E, CMTDI3, CMTDID, DSS
The encoded protein is a major structural glycoprotein of peripheral myelin that forms and stabilizes the compact myelin sheath in Schwann cells. Mutations cause a spectrum of autosomal dominant and recessive peripheral neuropathies including Charcot-Marie-Tooth disease types 1B and 2I/2J, Dejerine-Sottas disease, congenital hypomyelinating neuropathy, and Roussy-Levy syndrome. The pathogenic mechanism involves dominant-negative effects that disrupt normal myelin formation and maintenance.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MPZ · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools