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PMP22 gene
URL of this page: https://medlineplus.gov/genetics/gene/pmp22/

PMP22 gene

peripheral myelin protein 22

Normal Function

The PMP22 gene provides instructions for making a protein called peripheral myelin protein 22 (PMP22). This protein is found in peripheral nerves, which connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat.

The PMP22 protein is a component of myelin, a fatty substance that insulates nerve fibers and helps nerve impulses travel efficiently. Myelin is produced by Schwann cells, which wrap around nerve fibers many times to form multilayered myelin sheaths. The PMP22 protein is primarily found in these cells, where it plays a crucial role in the development and maintenance of myelin.

Studies suggest that the PMP22 protein is particularly important in helping nerves restore their structure after being pinched or squeezed (compressed). Compression can interrupt nerve signaling, leading to the sensation commonly referred to as a body part "falling asleep." The ability of nerves to recover from normal compression, such as sitting in one position for a long time, prevents body parts from repeatedly going numb.

Before PMP22 proteins become part of myelin, they must be processed and folded inside the cell. Completion of these steps is critical for proper myelin function.

Health Conditions Related to Genetic Changes

Charcot-Marie-Tooth disease

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the PMP22 gene cause a neurological disorder called Charcot-Marie-Tooth disease. This disorder damages the peripheral nerves, which results in muscle weakness and sensory problems, especially in the hands and feet.

An extra copy of the PMP22 gene is the most common genetic change that causes a form of Charcot-Marie-Tooth disease called type 1A (CMT1A). This extra copy occurs when genetic material on chromosome 17 is abnormally copied (duplicated). In most affected individuals, the duplicated segment includes approximately 1.4 million DNA building blocks (base pairs), also written as 1.4 megabases (Mb). This duplicated region includes about 15 genes, one of which is the PMP22 gene. An extra copy of the PMP22 gene leads to an overproduction of the PMP22 protein. 

Excess PMP22 protein disrupts the function of Schwann cells. This disruption impairs the formation of myelin (dysmyelination) and the maintenance of myelin (demyelination). Without properly functioning myelin, nerve signals slow down, resulting in the characteristic weakness and sensory loss seen in people with CMT1A. People with this condition experience signs and symptoms that typically begin in childhood or adolescence and gradually worsen over time.

Some pathogenic variants in the PMP22 gene that lead to a change in a single protein building block (amino acid) in the PMP22 protein cause a form of Charcot-Marie-Tooth disease called type 1E (CMT1E). This change can alter the structure of the PMP22 protein and prevent it from folding correctly, reaching the cell membrane, or functioning normally. The abnormal protein may accumulate inside Schwann cells or disrupt normal myelin structure. As a result, myelin does not form or function properly, leading to nerve damage. In addition to muscle weakness and sensory problems, some people with CMT1E develop hearing loss.

Other pathogenic variants in the PMP22 gene cause a severe form of Charcot-Marie-Tooth disease known as type 3 (CMT3), which was historically called Dejerine-Sottas syndrome (DSS). CMT3 typically begins in infancy or early childhood and is characterized by muscle weakness, loss of sensation, and delayed development of motor skills such as walking. The variants that cause CMT3 are thought to severely disrupt PMP22 protein function in Schwann cells, causing the signs and symptoms of CMT3.

More About This Health Condition

Hereditary neuropathy with liability to pressure palsies

The most common cause of hereditary neuropathy with liability to pressure palsies (HNPP) is the loss of one copy of the PMP22 gene. This occurs when genetic material is deleted from chromosome 17. This disorder is characterized by recurrent episodes of numbness, tingling, or loss of muscle function that are usually triggered by pressure on a nerve in an arm or leg. In most affected individuals, approximately 1.4 Mb of DNA are deleted from chromosome 17.

The deletion of one copy of the PMP22 gene reduces the amount of PMP22 protein produced by about half. HNPP can also be caused by pathogenic variants in the PMP22 gene that change single amino acids in the PMP22 protein or by pathogenic variants that lead to the production of an abnormally short protein that is rapidly broken down. Reduced PMP22 levels likely affect the structure of myelin, leading to nerve damage. This makes nerves more susceptible to injury and reduces their ability to recover from pressure or minor trauma, leading to the signs and symptoms of HNPP.

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Yuan-Harel-Lupski syndrome

Duplication of a small piece of chromosome 17 that includes the PMP22 gene can cause Yuan-Harel-Lupski (YUHAL) syndrome. YUHAL syndrome is characterized by neurological problems that are similar to those seen in people with Charcot-Marie-Tooth disease. In people with YUHAL syndrome, the duplicated segment ranges in size from about 3 Mb to nearly 20 Mb. This segment always contains the PMP22 gene and a nearby gene called RAI1; it may also include additional genes. Certain features of YUHAL syndrome, including muscle weakness and decreased sensitivity to touch, heat, and cold in the lower legs and feet, are likely due to the duplication of the PMP22 gene. Other features, such as developmental delays and behavioral problems, are likely caused by an extra copy of the RAI1 gene.

More About This Health Condition

Other Names for This Gene

  • GAS-3
  • GAS3
  • growth arrest-specific 3
  • HNPP
  • MGC20769
  • Sp110

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bai Y, Zhang X, Katona I, Saporta MA, Shy ME, O'Malley HA, Isom LL, Suter U, Li J. Conduction block in PMP22 deficiency. J Neurosci. 2010 Jan 13;30(2):600-8. doi: 10.1523/JNEUROSCI.4264-09.2010. Citation on PubMed or Free article on PubMed Central
  • Bird TD. Charcot-Marie-Tooth Hereditary Neuropathy Overview. 1998 Sep 28 [updated 2025 Nov 20]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1358/ Citation on PubMed
  • Boutary S, Echaniz-Laguna A, Adams D, Loisel-Duwattez J, Schumacher M, Massaad C, Massaad-Massade L. Treating PMP22 gene duplication-related Charcot-Marie-Tooth disease: the past, the present and the future. Transl Res. 2021 Jan;227:100-111. doi: 10.1016/j.trsl.2020.07.006. Epub 2020 Jul 18. Citation on PubMed
  • Guo J, Wang L, Zhang Y, Wu J, Arpag S, Hu B, Imhof BA, Tian X, Carter BD, Suter U, Li J. Abnormal junctions and permeability of myelin in PMP22-deficient nerves. Ann Neurol. 2014 Feb;75(2):255-65. doi: 10.1002/ana.24086. Epub 2014 Feb 20. Citation on PubMed or Free article on PubMed Central
  • Jetten AM, Suter U. The peripheral myelin protein 22 and epithelial membrane protein family. Prog Nucleic Acid Res Mol Biol. 2000;64:97-129. doi: 10.1016/s0079-6603(00)64003-5. Citation on PubMed
  • Katona I, Wu X, Feely SM, Sottile S, Siskind CE, Miller LJ, Shy ME, Li J. PMP22 expression in dermal nerve myelin from patients with CMT1A. Brain. 2009 Jul;132(Pt 7):1734-40. doi: 10.1093/brain/awp113. Epub 2009 May 15. Citation on PubMed or Free article on PubMed Central
  • Niedrist D, Joncourt F, Matyas G, Muller A. Severe phenotype with cis-acting heterozygous PMP22 mutations. Clin Genet. 2009 Mar;75(3):286-9. doi: 10.1111/j.1399-0004.2008.01120.x. Epub 2008 Nov 29. Citation on PubMed
  • Niemann A, Berger P, Suter U. Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):217-42. doi: 10.1385/nmm:8:1-2:217. Citation on PubMed
  • Rosso G, Liashkovich I, Gess B, Young P, Kun A, Shahin V. Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22. Sci Rep. 2014 Dec 2;4:7286. doi: 10.1038/srep07286. Citation on PubMed or Free article on PubMed Central
  • Rossor AM, Polke JM, Houlden H, Reilly MM. Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat Rev Neurol. 2013 Oct;9(10):562-71. doi: 10.1038/nrneurol.2013.179. Epub 2013 Sep 10. Citation on PubMed
  • Stavrou M, Kleopa KA. CMT1A current gene therapy approaches and promising biomarkers. Neural Regen Res. 2023 Jul;18(7):1434-1440. doi: 10.4103/1673-5374.361538. Citation on PubMed
  • Yuan B, Harel T, Gu S, Liu P, Burglen L, Chantot-Bastaraud S, Gelowani V, Beck CR, Carvalho CM, Cheung SW, Coe A, Malan V, Munnich A, Magoulas PL, Potocki L, Lupski JR. Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome. Am J Hum Genet. 2015 Nov 5;97(5):691-707. doi: 10.1016/j.ajhg.2015.10.003. Citation on PubMed or Free article on PubMed Central

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