PMP22
Chr 17ADARperipheral myelin protein 22
Also known as: CIDP, CMT1A, CMT1E, DSS, GAS-3, GAS3, HMSNIA, HNPP
PMP22 encodes peripheral myelin protein 22, a component of the myelin Schwann cells wrap around peripheral nerves, and its disorders are mostly about dosage. A 1.4 Mb duplication of 17p12 that contains the gene (three copies) causes CMT1A, the commonest Charcot-Marie-Tooth disease: 43% of genetic diagnoses in a UK cohort of 1,165. The reciprocal deletion (one copy) causes hereditary neuropathy with liability to pressure palsies (HNPP). Both arise from recombination between repeats flanking the segment.
Across 4,291 genetically characterised patients, 75.6% had the duplication, 19.6% the deletion and 4.8% a sequence variant. Sequence variants cause CMT1E (onset in childhood or adolescence, more often with hearing or eye involvement), Dejerine–Sottas syndrome (early and severe) and a small share of HNPP (loss-of-function variants that copy the deletion).
CMT1A is a demyelinating neuropathy that usually presents with distal weakness and foot drop; HNPP with recurrent palsies at entrapment sites such as the peroneal and ulnar nerves. Test copy number first (MLPA): exome data can miss the duplication and deletion, and sequencing is for the copy-number-negative.
Primary Disease Associations & Inheritance
Clinical highlights
PMP22 disease is mostly copy number
Each bar is one chromosome 17; each box the 1.4 Mb segment of 17p12 that carries PMP22. Repeats flanking the segment let it be duplicated on one chromosome and lost from the other.
2 copies → Normal
3 copies → CMT1A
75.6%Duplication of the segment. Demyelinating neuropathy, usually distal weakness and foot drop. Open in the CNV tool →
1 copy → HNPP
19.6%The reciprocal deletion. Recurrent palsies at entrapment sites (peroneal, ulnar). Open in the CNV tool →
2 copies, one altered → CMT1E · Dejerine–Sottas · rarely HNPP
4.8%A sequence variant in PMP22 itself.
Testing: copy number first (MLPA). Exome data can miss the duplication and the deletion, so a normal exome does not exclude them; sequence PMP22 when copy number is normal.
Percentages: share of 4,291 genetically characterised patients with PMP22 disease. Sources: Cesaroni et al., Genes (Basel) 2025 (systematic review); Record et al., Brain 2024; Sanders et al., Chem Rev 2026.
ClinVar Variant Classifications
0 submitted variants in 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
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
RECRUITINGGenetics of Charcot Marie Tooth (CMT) - Modifiers of CMT1A, New Causes of CMT2
RECRUITINGA Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)
RECRUITINGIdentification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease
RECRUITINGExternal Resources
Links to major genomics databases and tools