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Genetics Home Reference: your guide to understanding genetic conditions
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GJB3

Reviewed January 2014

What is the official name of the GJB3 gene?

The official name of this gene is “gap junction protein, beta 3, 31kDa.”

GJB3 is the gene's official symbol. The GJB3 gene is also known by other names, listed below.

What is the normal function of the GJB3 gene?

The GJB3 gene provides instructions for making a protein called gap junction beta 3, more commonly known as connexin 31. This protein is part of the connexin family, a group of proteins that form channels called gap junctions on the surface of cells. Gap junctions open and close to regulate the flow of nutrients, charged atoms (ions), and other signaling molecules from one cell to another. They are essential for direct communication between neighboring cells.

Connexin 31 is found in several different parts of the body, including the outermost layer of the skin (the epidermis) and structures of the inner ear. Connexin 31 plays a role in the growth and maturation of cells in the epidermis. The exact role of this protein in the inner ear is less clear, although it appears to be involved in hearing.

Does the GJB3 gene share characteristics with other genes?

The GJB3 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 GJB3 gene related to health conditions?

erythrokeratodermia variabilis et progressiva - caused by mutations in the GJB3 gene

At least 10 GJB3 gene mutations have been identified in people with erythrokeratodermia variabilis et progressiva (EKVP), a skin disorder characterized by areas of hyperkeratosis, which is abnormally thickened skin, and temporarily reddened patches called erythematous areas. Each of these mutations changes a single protein building block (amino acid) used to make connexin 31. Studies suggest that the abnormal protein can build up in a cell structure called the endoplasmic reticulum (ER), triggering a harmful process known as ER stress. Researchers suspect that ER stress damages and leads to the premature death of cells in the epidermis. This cell death leads to skin inflammation, which appears to underlie the development of erythematous areas. The mechanism by which epidermal damage and cell death contributes to hyperkeratosis is poorly understood.

nonsyndromic deafness - caused by mutations in the GJB3 gene

Researchers have identified several GJB3 gene mutations in people with nonsyndromic deafness, which is hearing loss without related signs and symptoms affecting other parts of the body. These mutations can cause a form of nonsyndromic deafness known as DFNA2B, which is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of the gene in each cell is altered. GJB3 gene mutations can also cause nonsyndromic deafness that is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell are altered.

GJB3 gene mutations related to hearing loss alter the sequence of protein building blocks (amino acids) in connexin 31. Some mutations lead to missing amino acids in connexin 31, while other mutations change single amino acids. These changes likely alter the 3-dimensional shape or size of connexin 31, which probably disrupts the assembly or function of gap junctions in the inner ear. It is unclear how changes in gap junctions contribute to hearing loss. It is also unclear why some mutations in the GJB3 gene are associated with deafness while others cause the skin problems characteristic of EKVP.

Where is the GJB3 gene located?

Cytogenetic Location: 1p34

Molecular Location on chromosome 1: base pairs 34,781,188 to 34,786,365

The GJB3 gene is located on the short (p) arm of chromosome 1 at position 34.

The GJB3 gene is located on the short (p) arm of chromosome 1 at position 34.

More precisely, the GJB3 gene is located from base pair 34,781,188 to base pair 34,786,365 on chromosome 1.

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 GJB3?

You and your healthcare professional may find the following resources about GJB3 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 GJB3 gene or gene products?

  • connexin 31
  • CX31
  • CXB3_HUMAN
  • DFNA2
  • PNHI

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 GJB3?

acids ; amino acid ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; connexin ; endoplasmic reticulum ; epidermis ; ER ; gap junctions ; gene ; inflammation ; inheritance ; inherited ; ions ; oxygen ; protein ; reactive oxygen species ; recessive ; stress

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

References

  • Chi J, Li L, Liu M, Tan J, Tang C, Pan Q, Wang D, Zhang Z. Pathogenic connexin-31 forms constitutively active hemichannels to promote necrotic cell death. PLoS One. 2012;7(2):e32531. doi: 10.1371/journal.pone.0032531. Epub 2012 Feb 29. (http://www.ncbi.nlm.nih.gov/pubmed/22393412?dopt=Abstract)
  • Diestel S, Richard G, Döring B, Traub O. Expression of a connexin31 mutation causing erythrokeratodermia variabilis is lethal for HeLa cells. Biochem Biophys Res Commun. 2002 Aug 23;296(3):721-8. (http://www.ncbi.nlm.nih.gov/pubmed/12176042?dopt=Abstract)
  • Liu XZ, Xia XJ, Xu LR, Pandya A, Liang CY, Blanton SH, Brown SD, Steel KP, Nance WE. Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss. Hum Mol Genet. 2000 Jan 1;9(1):63-7. (http://www.ncbi.nlm.nih.gov/pubmed/10587579?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2707)
  • Oh SK, Choi SY, Yu SH, Lee KY, Hong JH, Hur SW, Kim SJ, Jeon CJ, Kim UK. Evaluation of the pathogenicity of GJB3 and GJB6 variants associated with nonsyndromic hearing loss. Biochim Biophys Acta. 2013 Jan;1832(1):285-91. doi: 10.1016/j.bbadis.2012.05.009. Epub 2012 May 19. (http://www.ncbi.nlm.nih.gov/pubmed/22617145?dopt=Abstract)
  • 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)
  • Richard G, Smith LE, Bailey RA, Itin P, Hohl D, Epstein EH Jr, DiGiovanna JJ, Compton JG, Bale SJ. Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis. Nat Genet. 1998 Dec;20(4):366-9. (http://www.ncbi.nlm.nih.gov/pubmed/9843209?dopt=Abstract)
  • Scott CA, O'Toole EA, Mohungoo MJ, Messenger A, Kelsell DP. Novel and recurrent connexin 30.3 and connexin 31 mutations associated with erythrokeratoderma variabilis. Clin Exp Dermatol. 2011 Jan;36(1):88-90. (http://www.ncbi.nlm.nih.gov/pubmed/21188847?dopt=Abstract)
  • Xia JH, Liu CY, Tang BS, Pan Q, Huang L, Dai HP, Zhang BR, Xie W, Hu DX, Zheng D, Shi XL, Wang DA, Xia K, Yu KP, Liao XD, Feng Y, Yang YF, Xiao JY, Xie DH, Huang JZ. Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Nat Genet. 1998 Dec;20(4):370-3. Erratum in: Nat Genet 1999 Feb;21(2):241. (http://www.ncbi.nlm.nih.gov/pubmed/9843210?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: January 2014
Published: December 22, 2014