PMP2

Chr 8AD

peripheral myelin protein 2

Also known as: CMT1G, FABP8, M-FABP, MP2, P2

NCBI Gene: 5375ENSG00000147588UniProt: P02689

The protein encoded by this gene localizes to myelin sheaths of the peripheral nervous system. The encoded protein can bind both the membrane layers of the sheaths and monomeric lipids, and is thought to provide stability to the sheath. A defect in this gene was shown to be a cause of dominant demyelinating CMT neuropathy. [provided by RefSeq, Jan 2017]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, demyelinating, type 1GMIM #618279
AD
177
ClinVar variants
37
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— PMP2
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 88 VUS of 177 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.30LOEUF
pLI 0.008
Z-score 1.05
OE 0.57 (0.28–1.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.10Z-score
OE missense 0.97 (0.79–1.18)
67 obs / 69.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.28–1.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.79–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 4 / 7.0Missense obs/exp: 67 / 69.3Syn Z: 0.55

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic5
VUS88
Likely Benign41
Benign10
Conflicting1
32
Pathogenic
5
Likely Pathogenic
88
VUS
41
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
31
0
32
Likely Pathogenic
0
4
1
0
5
VUS
4
58
25
1
88
Likely Benign
0
8
24
9
41
Benign
0
4
5
1
10
Conflicting
—1
Total4758611177

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PMP2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, demyelinating, type 1G

MIM #618279

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PMP2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas.
Wang P et al.·Neuron
2025
A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy.
Hong YB et al.·PLoS Genet
2016
Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients with Charcot-Marie-Tooth.
Zhao X et al.·Chin Med J (Engl)
2018Cohort
Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells.
Noguchi R et al.·Hum Cell
2024
Identification of a pathogenic PMP2 variant in a multi-generational family with CMT type 1: Clinical gene panels versus genome-wide approaches to molecular diagnosis.
Punetha J et al.·Mol Genet Metab
2018Case report
De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease.
Motley WW et al.·Brain
2016
New developments in Charcot-Marie-Tooth neuropathy and related diseases.
Pareyson D et al.·Curr Opin Neurol
2017Review
Peripheral myelin protein 2 - a novel cluster of mutations causing Charcot-Marie-Tooth neuropathy.
Palaima P et al.·Orphanet J Rare Dis
2019
Protein Biomarkers of Cardiovascular Disease and Mortality in the Community.
Ho JE et al.·J Am Heart Assoc
2018
Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs.
Kraft T et al.·Acta Neuropathol Commun
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools