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Genetics Home Reference: your guide to understanding genetic conditions
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GJB1

Reviewed August 2009

What is the official name of the GJB1 gene?

The official name of this gene is “gap junction protein, beta 1, 32kDa.”

GJB1 is the gene's official symbol. The GJB1 gene is also known by other names, listed below.

What is the normal function of the GJB1 gene?

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.

The 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 around certain nerve cells and 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.

Does the GJB1 gene share characteristics with other genes?

The GJB1 gene belongs to a family of genes called GJ (gap junction proteins (connexins)).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the GJB1 gene related to health conditions?

Charcot-Marie-Tooth disease - caused by mutations in the GJB1 gene

Researchers have identified approximately 300 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. Some GJB1 gene mutations result in a protein of abnormal size.

It is unclear how GJB1 gene 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 degraded 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, such as 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, evidence of demyelination 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 did not generally cause any symptoms, but were identified by electrical testing of nerve impulses or imaging studies. 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.

Where is the GJB1 gene located?

Cytogenetic Location: Xq13.1

Molecular Location on the X chromosome: base pairs 71,215,211 to 71,225,214

The GJB1 gene is located on the long (q) arm of the X chromosome at position 13.1.

The GJB1 gene is located on the long (q) arm of the X chromosome at position 13.1.

More precisely, the GJB1 gene is located from base pair 71,215,211 to base pair 71,225,214 on the X chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about GJB1?

You and your healthcare professional may find the following resources about GJB1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the GJB1 gene or gene products?

  • CMTX
  • CMTX1
  • connexin 32
  • CX32
  • CXB1_HUMAN
  • gap junction protein, beta 1, 32kDa (connexin 32, Charcot-Marie-Tooth neuropathy, X-linked)

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding GJB1?

acids ; cell ; cell membrane ; central nervous system ; charged particles ; connexin ; demyelination ; gap junctions ; gene ; imaging ; ions ; kidney ; myelin sheath ; nerve cell ; nervous system ; neuropathy ; oligodendrocytes ; pancreas ; peripheral ; peripheral nervous system ; protein ; Schwann cells ; sensory cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Abrams CK, Oh S, Ri Y, Bargiello TA. Mutations in connexin 32: the molecular and biophysical bases for the X-linked form of Charcot-Marie-Tooth disease. Brain Res Brain Res Rev. 2000 Apr;32(1):203-14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10751671?dopt=Abstract)
  • Baker SK, Reith CC, Ainsworth PJ. Novel 95G>A (R32K) somatic mosaic connexin 32 mutation. Muscle Nerve. 2008 Nov;38(5):1510-4. doi: 10.1002/mus.21145. (http://www.ncbi.nlm.nih.gov/pubmed/18949782?dopt=Abstract)
  • Kleopa KA, Scherer SS. Molecular genetics of X-linked Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):107-22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16775370?dopt=Abstract)
  • Kochański A, Kabzińska D. Molecular genetic analysis of the GJB1 gene: a study of six mutations. J Appl Genet. 2004;45(1):95-100. (http://www.ncbi.nlm.nih.gov/pubmed/14960772?dopt=Abstract)
  • Mandich P, Grandis M, Geroldi A, Acquaviva M, Varese A, Gulli R, Ciotti P, Bellone E. Gap junction beta 1 (GJB1) gene mutations in Italian patients with X-linked Charcot-Marie-Tooth disease. J Hum Genet. 2008;53(6):529-33. doi: 10.1007/s10038-008-0280-4. Epub 2008 Apr 1. (http://www.ncbi.nlm.nih.gov/pubmed/18379723?dopt=Abstract)
  • Mazzeo A, Di Leo R, Toscano A, Muglia M, Patitucci A, Messina C, Vita G. Charcot-Marie-Tooth type X: unusual phenotype of a novel CX32 mutation. Eur J Neurol. 2008 Oct;15(10):1140-2. doi: 10.1111/j.1468-1331.2008.02263.x. Epub 2008 Aug 20. (http://www.ncbi.nlm.nih.gov/pubmed/18717720?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2705)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/10751670?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/19369543?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15006706?dopt=Abstract)
  • Young P, Suter U. The causes of Charcot-Marie-Tooth disease. Cell Mol Life Sci. 2003 Dec;60(12):2547-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14685682?dopt=Abstract)
  • Zambelis T, Panas M, Kokotis P, Karadima G, Kararizou E, Karandreas N. Central motor and sensory pathway involvement in an X-linked Charcot-Marie-Tooth family. Acta Neurol Belg. 2008 Jun;108(2):44-7. (http://www.ncbi.nlm.nih.gov/pubmed/18795595?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2009
Published: July 7, 2014