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GJB1 gene
URL of this page: https://medlineplus.gov/genetics/gene/gjb1/

GJB1 gene

gap junction protein beta 1

Normal Function

The GJB1 gene provides instructions for making a protein called gap junction beta 1, also known as connexin 32 (Cx32). This protein belongs to the connexin family, which enables communication between neighboring cells by forming channels between cells called gap junctions. Gap junctions allow charged particles (ions), nutrients, and small signaling molecules to pass between cells.

The gap junction beta 1 protein is made in several tissues, but it is especially important 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. In the nervous system, the gap junction beta 1 protein is located in the cell membrane of specialized cells called Schwann cells and oligodendrocytes. Schwann cells wrap around peripheral nerves, and oligodendrocytes wrap around nerve cells in the brain and spinal cord (central nervous system).

Schwann cells and oligodendrocytes produce myelin, a fatty substance that insulates nerve fibers and helps transmit nerve impulses efficiently. In Schwann cells, gap junction beta 1 proteins form channels within the layers of myelin that allow communication between the outer layers of the myelin sheath and the inner portion of the cell.

Health Conditions Related to Genetic Changes

Charcot-Marie-Tooth disease

Genetic changes that cause disease are called pathogenic variants. Hundreds of pathogenic variants in the GJB1 gene have been found to cause a neurological disorder called Charcot-Marie-Tooth disease. This disorder damages the peripheral nerves, which results in muscle weakness and the loss of sensation, especially in the hands and feet. GJB1 gene variants cause a form of Charcot-Marie-Tooth disease called type X (CMTX), also known as CMTX1 or CMT1X.

Most pathogenic variants in the GJB1 gene lead to a substitution of one protein building block (amino acid) for another in the gap junction beta 1 protein. Some of these variants prevent cells from producing the gap junction beta 1 protein, while others cause cells to produce an altered version of the protein that does not function properly. The altered protein may break down quickly or become trapped inside the cell, preventing it from reaching the cell membrane to form gap junctions. In some cases, the altered protein reaches the cell membrane but does not form normal gap junctions. The loss of functional gap junctions likely impairs the normal activities of Schwann cells, including myelin production. Without normal gap junctions, communication within Schwann cells and between Schwann cells and the underlying nerve fibers is impaired, which disturbs the transmission of nerve impulses and causes the muscle weakness and sensory problems seen in people with Charcot-Marie-Tooth disease.

Changes in the GJB1 gene can affect myelin-producing cells in both the peripheral and central nervous systems. However, the peripheral nerves are usually more severely affected. In addition to the peripheral nervous system problems, some individuals with Charcot-Marie-Tooth disease caused by GJB1 gene variants have changes in the brain that reflect the loss of myelin in the central nervous system. This causes neurological symptoms in some affected individuals, although they are often mild or may not occur all the time.

More About This Health Condition

Other Names for This Gene

  • CMTX
  • CMTX1
  • connexin 32
  • CX32

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

  • Abrams CK, Freidin M. GJB1-associated X-linked Charcot-Marie-Tooth disease, a disorder affecting the central and peripheral nervous systems. Cell Tissue Res. 2015 Jun;360(3):659-73. doi: 10.1007/s00441-014-2014-6. Epub 2014 Nov 5. Citation on PubMed
  • Abrams CK. GJB1 Disorders: Charcot-Marie-Tooth Neuropathy (CMT1X) and Central Nervous System Phenotypes. 1998 Jun 18 [updated 2024 Apr 25]. 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/NBK1374/ Citation on PubMed
  • Fridman V, Saporta MA. Mechanisms and Treatments in Demyelinating CMT. Neurotherapeutics. 2021 Oct;18(4):2236-2268. doi: 10.1007/s13311-021-01145-z. Epub 2021 Nov 8. Citation on PubMed
  • Kleopa KA, Sargiannidou I. Connexins, gap junctions and peripheral neuropathy. Neurosci Lett. 2015 Jun 2;596:27-32. doi: 10.1016/j.neulet.2014.10.033. Epub 2014 Oct 24. Citation on PubMed
  • Record CJ, Skorupinska M, Laura M, Rossor AM, Pareyson D, Pisciotta C, Feely SME, Lloyd TE, Horvath R, Sadjadi R, Herrmann DN, Li J, Walk D, Yum SW, Lewis RA, Day J, Burns J, Finkel RS, Saporta MA, Ramchandren S, Weiss MD, Acsadi G, Fridman V, Muntoni F, Poh R, Polke JM, Zuchner S, Shy ME, Scherer SS, Reilly MM; Inherited Neuropathies Consortium-Rare Disease Clinical Research Network. Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants. Brain. 2023 Oct 3;146(10):4336-4349. doi: 10.1093/brain/awad187. Citation on PubMed
  • Ressot C, Bruzzone R. Connexin channels in Schwann cells and the development of the X-linked form of Charcot-Marie-Tooth disease. Brain Res Brain Res Rev. 2000 Apr;32(1):192-202. doi: 10.1016/s0165-0173(99)00081-8. Citation on PubMed
  • Sargiannidou I, Markoullis K, Kleopa KA. Molecular mechanisms of gap junction mutations in myelinating cells. Histol Histopathol. 2010 Sep;25(9):1191-206. doi: 10.14670/HH-25.1191. Citation on PubMed
  • Sargiannidou I, Vavlitou N, Aristodemou S, Hadjisavvas A, Kyriacou K, Scherer SS, Kleopa KA. Connexin32 mutations cause loss of function in Schwann cells and oligodendrocytes leading to PNS and CNS myelination defects. J Neurosci. 2009 Apr 15;29(15):4736-49. doi: 10.1523/JNEUROSCI.0325-09.2009. Citation on PubMed or Free article on PubMed Central
  • Scherer SS, Kleopa KA. X-linked Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2012 Dec;17 Suppl 3(0 3):9-13. doi: 10.1111/j.1529-8027.2012.00424.x. Citation on PubMed or Free article on PubMed Central
  • Wang HL, Chang WT, Yeh TH, Wu T, Chen MS, Wu CY. Functional analysis of connexin-32 mutants associated with X-linked dominant Charcot-Marie-Tooth disease. Neurobiol Dis. 2004 Mar;15(2):361-70. doi: 10.1016/j.nbd.2003.11.005. Citation on PubMed
  • Wang Y, Yin F. A Review of X-linked Charcot-Marie-Tooth Disease. J Child Neurol. 2016 May;31(6):761-72. doi: 10.1177/0883073815604227. Epub 2015 Sep 18. Citation on PubMed

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