PLP1

Chr XXLR

proteolipid protein 1

Also known as: GPM6C, HLD1, MMPL, PLP, PLP/DM20, PMD, SPG2

NCBI Gene: 5354ENSG00000123560UniProt: P60201

The protein is a transmembrane proteolipid that serves as the predominant component of myelin and functions in the compaction, stabilization, and maintenance of myelin sheaths. Mutations cause Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2, inherited in an X-linked recessive pattern. The pathogenic mechanism involves disrupted myelin formation and maintenance, affecting oligodendrocyte development and axonal survival.

Summary from RefSeq, OMIM, UniProt

Primary Disease Associations & Inheritance

Pelizaeus-Merzbacher diseaseMIM #312080
XLR
Spastic paraplegia 2, X-linkedMIM #312920
XLR
UniProtLeukodystrophy, hypomyelinating, 1
1
Active trials
56
Pubs (1 yr)
317
P/LP submissions
23%
P/LP missense
0.35
LOEUF
LOF
Mechanism· G2P
Clinical Summary— PLP1
🧬
Gene-Disease Validity (ClinGen)
Pelizeaus-Merzbacher spectrum disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
265 unique Pathogenic / Likely Pathogenic· 118 VUS of 500 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — PLP1
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
0.35LOEUF
pLI 0.928
Z-score 2.69
OE 0.00 (0.00–0.35)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.04Z-score
OE missense 0.44 (0.34–0.56)
45 obs / 103.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.35)
0≤0.351.4
Missense OE0.44 (0.34–0.56)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 0 / 8.4Missense obs/exp: 45 / 103.3Syn Z: -0.14

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic173
Likely Pathogenic92
VUS118
Likely Benign63
Benign17
Conflicting12
173
Pathogenic
92
Likely Pathogenic
118
VUS
63
Likely Benign
17
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
8
140
0
173
Likely Pathogenic
24
52
13
3
92
VUS
4
86
26
2
118
Likely Benign
0
2
25
36
63
Benign
0
0
15
2
17
Conflicting
—12
Total5314821943475

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

View in ClinVar →

Protein Context — Lollipop Plot

PLP1 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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