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Genetics Home Reference: your guide to understanding genetic conditions
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GJB6

Reviewed March 2014

What is the official name of the GJB6 gene?

The official name of this gene is “gap junction protein, beta 6, 30kDa.”

GJB6 is the gene's official symbol. The GJB6 gene is also known by other names, listed below.

What is the normal function of the GJB6 gene?

The GJB6 gene provides instructions for making a protein called gap junction beta 6, more commonly known as connexin 30. Connexin 30 is a member of the connexin protein family. Connexin proteins form channels called gap junctions, which permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells. The size of the gap junction and the types of particles that move through it are determined by the particular connexin proteins that make up the channel. Gap junctions made with connexin 30 transport potassium ions and certain small molecules.

Connexin 30 is found in several different tissues throughout the body, including the brain, inner ear, skin (especially on the palms of the hands and soles of the feet), hair follicles, and nail beds. Because of its presence in the inner ear, researchers are interested in this protein's role in hearing. Hearing requires the conversion of sound waves to electrical nerve impulses. This conversion involves many processes, including maintaining the proper level of potassium ions in the inner ear. Some studies indicate that gap junctions made with connexin 30 help to maintain the correct level of potassium ions.

Does the GJB6 gene share characteristics with other genes?

The GJB6 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 GJB6 gene related to health conditions?

Clouston syndrome - caused by mutations in the GJB6 gene

At least four GJB6 gene mutations have been identified in people with a skin disorder called Clouston syndrome, which is also known as hidrotic ectodermal dysplasia 2. Characteristics of Clouston syndrome include fingernail abnormalities, hair loss, and thickened skin on the palms of the hands and soles of the feet. The GJB6 gene mutations that cause Clouston syndrome change single protein building blocks (amino acids) in the connexin 30 protein. Although the effects of these mutations are not fully understood, they lead to abnormalities in the growth, division, and maturation of cells in the hair follicles, nails, and skin.

nonsyndromic deafness - caused by mutations in the GJB6 gene

Researchers have identified a few GJB6 gene mutations in individuals with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB1. DFNB1 deafness is inherited in an autosomal recessive manner, which means that two copies of an altered gene in each cell are necessary to cause hearing loss. Some cases of DFNB1 deafness are caused by mutations that delete a large segment of DNA in both copies of the GJB6 gene. More commonly, however, a deletion occurs in one copy of the GJB6 gene, and a different mutation occurs in one copy of a neighboring gene called GJB2. Although the effect of a deletion in the GJB6 gene is unclear, it probably reduces the number of functional gap junctions. As a result, the proper level of potassium ions in the inner ear could be disturbed, disrupting the conversion of sound waves to nerve impulses.

One GJB6 gene mutation has been reported in individuals with a form of nonsyndromic deafness called DFNA3, which is inherited in an autosomal dominant manner. This type of inheritance means that one copy of an altered GJB6 gene in each cell is sufficient to cause hearing loss. The GJB6 gene mutation changes one of the amino acids used to make connexin 30. In this case, the amino acid threonine is replaced by the amino acid methionine at protein position 5 (written as Thr5Met). Although the effect of this replacement is not fully understood, it appears to inhibit the activity of gap junctions. As a result, the proper level of potassium ions in the inner ear could be disturbed, disrupting the conversion of sound waves to nerve impulses.

Where is the GJB6 gene located?

Cytogenetic Location: 13q12

Molecular Location on chromosome 13: base pairs 20,221,961 to 20,232,394

The GJB6 gene is located on the long (q) arm of chromosome 13 at position 12.

The GJB6 gene is located on the long (q) arm of chromosome 13 at position 12.

More precisely, the GJB6 gene is located from base pair 20,221,961 to base pair 20,232,394 on chromosome 13.

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 GJB6?

You and your healthcare professional may find the following resources about GJB6 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 GJB6 gene or gene products?

  • CX30
  • CXB6_HUMAN
  • DFNA3
  • ED2
  • EDH
  • gap junction protein, beta 6
  • HED

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 GJB6?

acids ; amino acid ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; channel ; connexin ; deletion ; DNA ; dysplasia ; gap junctions ; gene ; inheritance ; inherited ; ions ; methionine ; mutation ; potassium ; protein ; recessive ; syndrome ; threonine

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

References

  • Baris HN, Zlotogorski A, Peretz-Amit G, Doviner V, Shohat M, Reznik-Wolf H, Pras E. A novel GJB6 missense mutation in hidrotic ectodermal dysplasia 2 (Clouston syndrome) broadens its genotypic basis. Br J Dermatol. 2008 Dec;159(6):1373-6. doi: 10.1111/j.1365-2133.2008.08796.x. Epub 2008 Aug 19. (http://www.ncbi.nlm.nih.gov/pubmed/18717672?dopt=Abstract)
  • Common JE, Becker D, Di WL, Leigh IM, O'Toole EA, Kelsell DP. Functional studies of human skin disease- and deafness-associated connexin 30 mutations. Biochem Biophys Res Commun. 2002 Nov 15;298(5):651-6. (http://www.ncbi.nlm.nih.gov/pubmed/12419304?dopt=Abstract)
  • Essenfelder GM, Bruzzone R, Lamartine J, Charollais A, Blanchet-Bardon C, Barbe MT, Meda P, Waksman G. Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity. Hum Mol Genet. 2004 Aug 15;13(16):1703-14. Epub 2004 Jun 22. (http://www.ncbi.nlm.nih.gov/pubmed/15213106?dopt=Abstract)
  • Fujimoto A, Kurban M, Nakamura M, Farooq M, Fujikawa H, Kibbi AG, Ito M, Dahdah M, Matta M, Diab H, Shimomura Y. GJB6, of which mutations underlie Clouston syndrome, is a potential direct target gene of p63. J Dermatol Sci. 2013 Feb;69(2):159-66. doi: 10.1016/j.jdermsci.2012.11.005. Epub 2012 Nov 16. (http://www.ncbi.nlm.nih.gov/pubmed/23219093?dopt=Abstract)
  • Gene Review: Hidrotic Ectodermal Dysplasia 2 (http://www.ncbi.nlm.nih.gov/books/NBK1200)
  • Kibar Z, Der Kaloustian VM, Brais B, Hani V, Fraser FC, Rouleau GA. The gene responsible for Clouston hidrotic ectodermal dysplasia maps to the pericentromeric region of chromosome 13q. Hum Mol Genet. 1996 Apr;5(4):543-7. (http://www.ncbi.nlm.nih.gov/pubmed/8845850?dopt=Abstract)
  • Kibar Z, Dubé MP, Powell J, McCuaïg C, Hayflick SJ, Zonana J, Hovnanian A, Radhakrishna U, Antonarakis SE, Benohanian A, Sheeran AD, Stephan ML, Gosselin R, Kelsell DP, Christianson AL, Fraser FC, Der Kaloustian VM, Rouleau GA. Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping. Eur J Hum Genet. 2000 May;8(5):372-80. (http://www.ncbi.nlm.nih.gov/pubmed/10854098?dopt=Abstract)
  • Lamartine J, Munhoz Essenfelder G, Kibar Z, Lanneluc I, Callouet E, Laoudj D, Lemaître G, Hand C, Hayflick SJ, Zonana J, Antonarakis S, Radhakrishna U, Kelsell DP, Christianson AL, Pitaval A, Der Kaloustian V, Fraser C, Blanchet-Bardon C, Rouleau GA, Waksman G. Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nat Genet. 2000 Oct;26(2):142-4. (http://www.ncbi.nlm.nih.gov/pubmed/11017065?dopt=Abstract)
  • Marlin S, Feldmann D, Blons H, Loundon N, Rouillon I, Albert S, Chauvin P, Garabédian EN, Couderc R, Odent S, Joannard A, Schmerber S, Delobel B, Leman J, Journel H, Catros H, Lemarechal C, Dollfus H, Eliot MM, Delaunoy JL, David A, Calais C, Drouin-Garraud V, Obstoy MF, Goizet C, Duriez F, Fellmann F, Hélias J, Vigneron J, Montaut B, Matin-Coignard D, Faivre L, Baumann C, Lewin P, Petit C, Denoyelle F. GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients. Arch Otolaryngol Head Neck Surg. 2005 Jun;131(6):481-7. (http://www.ncbi.nlm.nih.gov/pubmed/15967879?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/10804)
  • Petersen MB, Willems PJ. Non-syndromic, autosomal-recessive deafness. Clin Genet. 2006 May;69(5):371-92. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16650073?dopt=Abstract)
  • Rabionet R, López-Bigas N, Arbonès ML, Estivill X. Connexin mutations in hearing loss, dermatological and neurological disorders. Trends Mol Med. 2002 May;8(5):205-12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12067629?dopt=Abstract)
  • Sabag AD, Dagan O, Avraham KB. Connexins in hearing loss: a comprehensive overview. J Basic Clin Physiol Pharmacol. 2005;16(2-3):101-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16285463?dopt=Abstract)
  • Smith FJ, Morley SM, McLean WH. A novel connexin 30 mutation in Clouston syndrome. J Invest Dermatol. 2002 Mar;118(3):530-2. (http://www.ncbi.nlm.nih.gov/pubmed/11874494?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: March 2014
Published: December 22, 2014