PLP1

Chr XXLR

proteolipid protein 1

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

NCBI Gene: 5354 ENSG00000123560 UniProt: P60201 OMIM: 300401

The protein encoded by this gene is a transmembrane proteolipid protein 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 through an X-linked recessive inheritance pattern. The gene is highly constrained against loss-of-function variants, and mutations can cause disease through multiple mechanisms depending on the specific variant type.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transmembrane proteolipid protein that is the predominant component of myelin. The encoded protein may play a role in the compaction, stabilization, and maintenance of myelin sheaths, as well as in oligodendrocyte development and axonal survival. Mutations in this gene cause Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Alternatively splicing results in multiple transcript variants, including the DM20 splice variant. [provided by RefSeq, Feb 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Pelizaeus-Merzbacher diseaseMIM #312080

XLR

Spastic paraplegia 2, X-linkedMIM #312920

XLR

UniProtLeukodystrophy, hypomyelinating, 1

Clinical highlights

Gene-disease validity (ClinGen)

Pelizaeus-Merzbacher spectrum disorder · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF

LOF

Mechanism· G2P

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GeneReview available — PLP1