MPZ

Chr 1ADAR

myelin protein zero

Also known as: CMT1, CMT1B, CMT2I, CMT2J, CMT4E, CMTDI3, CMTDID, DSS

NCBI Gene: 4359 ENSG00000158887 UniProt: P25189 OMIM: 159440

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is specifically expressed in Schwann cells of the peripheral nervous system and encodes a type I transmembrane glycoprotein that is a major structural protein of the peripheral myelin sheath. The encoded protein contains a large hydrophobic extracellular domain and a smaller basic intracellular domain, which are essential for the formation and stabilization of the multilamellar structure of the compact myelin. Mutations in this gene are associated with autosomal dominant form of Charcot-Marie-Tooth disease type 1 (CMT1B) and other polyneuropathies, such as Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). A recent study showed that two isoforms are produced from the same mRNA by use of alternative in-frame translation termination codons via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, dominant intermediate DMIM #607791

Charcot-Marie-Tooth disease, type 1BMIM #118200

Charcot-Marie-Tooth disease, type 2IMIM #607677

Charcot-Marie-Tooth disease, type 2JMIM #607736

Dejerine-Sottas diseaseMIM #145900

ADAR

Hypomyelinating neuropathy, congenital, 2MIM #618184

Roussy-Levy syndromeMIM #180800

UniProtAdie pupil

UniProtDejerine-Sottas syndrome

Clinical highlights

Gene-disease validity (ClinGen)

Charcot-Marie-Tooth disease · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Multiple*

Mechanism· predicted