PMP22

Chr 17ADAR

peripheral myelin protein 22

Also known as: CIDP, CMT1A, CMT1E, DSS, GAS-3, GAS3, HMSNIA, HNPP

NCBI Gene: 5376 ENSG00000109099 UniProt: Q9NR77 OMIM: 601097

This gene encodes an integral membrane protein that is a major component of myelin in the peripheral nervous system. Mutations cause several inherited peripheral neuropathies including Charcot-Marie-Tooth disease types 1A and 1E, Dejerine-Sottas disease, hereditary neuropathy with liability to pressure palsies, and Roussy-Levy syndrome, with inheritance patterns that are primarily autosomal dominant but can be autosomal recessive. The pathogenic mechanism involves disruption of peripheral myelin structure and function due to altered PMP22 protein levels or function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an integral membrane protein that is a major component of myelin in the peripheral nervous system. Studies suggest two alternately used promoters drive tissue-specific expression. Various mutations of this gene are causes of Charcot-Marie-Tooth disease Type IA, Dejerine-Sottas syndrome, and hereditary neuropathy with liability to pressure palsies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Neuropathy, inflammatory demyelinatingMIM #139393

Charcot-Marie-Tooth disease, type 1AMIM #118220

Charcot-Marie-Tooth disease, type 1EMIM #118300

Dejerine-Sottas diseaseMIM #145900

ADAR

Neuropathy, recurrent, with pressure palsiesMIM #162500

Roussy-Levy syndromeMIM #180800

Clinical highlights

Gene-disease validity (ClinGen)

Charcot-Marie-Tooth disease type 1A · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — PMP22

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.39LOEUF

pLI 0.910

Z-score 2.58

OE 0.00 (0.00–0.39)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.42Z-score

OE missense 0.88 (0.73–1.06)

79 obs / 90.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.39)

0≤0.351.4

Missense OE?0.88 (0.73–1.06)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 0 / 7.7Missense obs/exp: 79 / 90.1Syn Z: -0.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PMP22 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — PMP22

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

CMTCMT (Charcot Marie Tooth Disease)CMT - Charcot-Marie-Tooth Disease

A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)

RECRUITING

NCT07476365University Medical Center GoettingenStarted 2025-03-24

Charcot-Marie-Tooth Disease Type 1A

Clinical Trial Evaluating the Impact of an Intensive Rehabilitation Program Combined With Tendon Vibratory Stimulation on Functional Balance in Individuals With Charcot-Marie-Tooth Disease Type 1A

RECRUITING

NCT07726043Phase NAUGECAM PACA et CorseStarted 2025-04-28

Multidisciplinary rehabilitation program

Metastatic Solid TumorAdvanced Cancer

High Definition Medicine for Solid Tumors Oncology

RECRUITING

NCT06590506Centro Nacional de Investigaciones Oncologicas CARLOS IIIStarted 2023-03-02

Wearable

Charcot-Marie-Tooth Disease, Type Ia (Disorder)HMSN

Genetics of Charcot Marie Tooth (CMT) - Modifiers of CMT1A, New Causes of CMT2

RECRUITING

NCT01193088University of IowaStarted 2010-05