PMP22

Protein identityUniProt · HPA

UniProt accession

Q01453

Gene

PMP22

Ensembl

ENSG00000109099

Chromosome

17

Canonical length

160 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

160 residues, UniProt reviewed canonical sequence.

>Q01453|PMP22
     1  MLLLLLSIIV LHVAVLVLLF VSTIVSQWIV GNGHATDLWQ NCSTSSSGNV HHCFSSSPNE
    61  WLQSVQATMI LSIIFSILSL FLFFCQLFTL TKGGRFYITG IFQILAGLCV MSAAAIYTVR
   121  HPEWHLNSDY SYGFAYILAW VAFPLALLSG VIYVILRKRE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PMP22 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

4

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

246 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PMP22.

Disease | AllUniProt

Conditions PMP22 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, demyelinating, type 1A (CMT1A) MIM:118220
• Dejerine-Sottas syndrome (DSS) MIM:145900
• Hereditary neuropathy with liability to pressure palsies (HNPP) MIM:162500
• Charcot-Marie-Tooth disease, demyelinating, type 1E (CMT1E) MIM:118300
• Inflammatory demyelinating polyneuropathy (IDP) MIM:139393

Disease | GeneticClinVar

104 pathogenic / likely-pathogenic of 433 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Charcot-Marie-Tooth disease, type I
• Charcot-Marie-Tooth disease
• Charcot-Marie-Tooth disease, type IA
• Dejerine-Sottas disease
• Hereditary liability to pressure palsies

ReferencesPubMed · IEDB

Publications for PMP22 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.39

gnomAD pLI

0.91

gnomAD missense Z

0.42

DepMap mean gene effect

0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• bleb assembly
• cell differentiation
• chemical synaptic transmission
• myelin assembly
• negative regulation of cell population proliferation
• negative regulation of neuron projection development
• peripheral nervous system development

Cellular components

• bicellular tight junction
• compact myelin
• plasma membrane
• synapse

Protein domainsUniProt · Pfam · InterPro

• PMP-22/EMP/MP20/Claudin
• PMP-22/EMP/MP20
• Peripheral myelin protein 22/Epithelial membrane protein-like
• PMP-22/EMP/MP20/Claudin family
• Peripheral myelin protein PMP22

KeywordsUniProt

• Cell membrane
• Charcot-Marie-Tooth disease
• Deafness
• Dejerine-Sottas syndrome
• Glycoprotein
• Membrane
• Neurodegeneration
• Neuropathy
• Transmembrane
• Transmembrane helix
• Ubl conjugation