The GJB1 gene provides instructions for making a protein called connexin-32 (also known as gap junction beta 1). This protein is a member of the gap junction connexin family, which plays a role in cell communication by forming channels, or gap junctions, between cells. Gap junctions speed the transport of nutrients, charged particles (ions), and small molecules that carry communication signals between cells.
The connexin-32 protein is made in several tissues, including those of the liver, pancreas, kidney, and nervous system. In the nervous system, this protein is located in the cell membrane of specialized cells called Schwann cells and oligodendrocytes. Schwann cells are found in the peripheral nervous system, which consists of nerves connecting the brain and spinal cord (central nervous system) to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Oligodendrocytes are located in the central nervous system.
Schwann cells and oligodendrocytes surround nerves and are involved in the production and long-term maintenance of a fatty substance called myelin. Myelin forms a protective coating (or sheath) around certain nerve cells that ensures the smooth and rapid transmission of nerve impulses.
The connexin-32 protein forms channels through the myelin sheath, allowing efficient transport and communication between the outer myelin layers and the interior of the Schwann cell or oligodendrocyte.
Health Conditions Related to Genetic Changes
Researchers have identified more than 400 GJB1 gene mutations in people with type X Charcot-Marie-Tooth disease, a disorder characterized by muscle weakness and sensory problems, especially in the hands and feet. A few of these mutations also cause hearing loss in individuals with this type of Charcot-Marie-Tooth disease.
Most GJB1 gene mutations change single protein building blocks (amino acids) in the connexin-32 protein. It is unclear how these mutations lead to the characteristic features of Charcot-Marie-Tooth disease, including a loss of myelin (demyelination) and the slowed transmission of nerve impulses in the peripheral nervous system. The altered protein may be broken down quickly or trapped inside the cell, preventing it from reaching the cell membrane to form gap junctions. In some cases, an altered protein reaches the cell membrane but does not form properly functioning gap junctions. The loss of functional gap junctions probably impairs the normal activities of Schwann cells, including myelin production. Malfunctioning gap junctions could also disrupt communication between Schwann cells and the underlying nerve cell, disturbing the transmission of nerve impulses.
In addition to the peripheral nervous system problems associated with this disorder, loss of myelin in the central nervous system has been reported in some people with Charcot-Marie-Tooth disease caused by GJB1 gene mutations. These central nervous system abnormalities do not generally cause any symptoms. Research suggests that another connexin protein whose function overlaps with that of connexin-32 helps compensate for the mutated connexin-32 protein in the oligodendrocytes of the central nervous system.More About This Health Condition
Other Names for This Gene
- connexin 32
- gap junction protein, beta 1, 32kDa
- gap junction protein, beta 1, 32kDa (connexin 32, Charcot-Marie-Tooth neuropathy, X-linked)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- 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. Review. Citation on PubMed
- Baker SK, Reith CC, Ainsworth PJ. Novel 95G>A (R32K) somatic mosaic connexin 32 mutation. Muscle Nerve. 2008 Nov;38(5):1510-1514. doi: 10.1002/mus.21145. Citation on PubMed
- Kleopa KA, Abrams CK, Scherer SS. How do mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease? Brain Res. 2012 Dec 3;1487:198-205. doi: 10.1016/j.brainres.2012.03.068. Epub 2012 Jul 6. Review. Citation on PubMed or Free article on PubMed Central
- 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. Review. 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. Review. 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. Review. 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 3:9-13. doi: 10.1111/j.1529-8027.2012.00424.x. Review. 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. 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. Review. Citation on PubMed