|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “gap junction protein, beta 2, 26kDa.”
GJB2 is the gene's official symbol. The GJB2 gene is also known by other names, listed below.
The GJB2 gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. 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 26 transport potassium ions and certain small molecules.
Connexin 26 is found in cells throughout the body, including the inner ear and the skin. Because of its presence in the inner ear, especially the snail-shaped structure called the cochlea, 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 channels made with connexin 26 help to maintain the correct level of potassium ions. Other research suggests that connexin 26 is required for the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis).
The GJB2 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.
At least two GJB2 gene mutations have been identified in people with Bart-Pumphrey syndrome. This condition is characterized by a white discoloration of the nails (leukonychia), thickened skin on the palms of the hands and soles of the feet (palmoplantar keratoderma), wart-like growths (knuckle pads) on the knuckles of the fingers and toes, and hearing loss. The GJB2 gene mutations that cause Bart-Pumphrey syndrome replace the protein building block (amino acid) glycine with the amino acid serine at protein position 59 (Gly59Ser or G59S) or replace the amino acid asparagine with the amino acid lysine at protein position 54 (Asn54Lys or N54K). The altered protein probably disrupts the function of normal connexin 26 in cells. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses.
At least one GJB2 gene mutation has been identified in people with hystrix-like ichthyosis with deafness (HID), a disorder characterized by dry, scaly skin (ichthyosis) and hearing loss that is usually profound. This mutation replaces the amino acid aspartic acid with the amino acid asparagine at protein position 50, written as Asp50Asn or D50N. The mutation is thought to result in channels that constantly leak ions, which impairs the health of the cells and increases cell death. Death of cells in the skin and the inner ear may underlie the signs and symptoms of HID.
Because the D50N mutation can also cause keratitis-ichthyosis-deafness (KID) syndrome (described below), many researchers categorize KID syndrome and HID as a single disorder, which they call KID/HID. It is not known why some people with this mutation have eye problems while others do not.
At least nine GJB2 gene mutations have been identified in people with keratitis-ichthyosis-deafness (KID) syndrome, with the most common being the D50N mutation that also occurs in hystrix-like ichthyosis with deafness (described above). KID syndrome is characterized by keratitis, which is inflammation of the front surface of the eye (the cornea); thick, reddened patches of dry and scaly skin (ichthyosis); and deafness.
The GJB2 gene mutations that cause KID syndrome change single amino acids in connexin 26. The mutations are thought to result in channels that constantly leak ions, which impairs the health of the cells and increases cell death. Death of cells in the skin and the inner ear may underlie the ichthyosis and deafness that occur in KID syndrome. It is unclear how GJB2 gene mutations affect the eye.
Researchers have identified more than 90 GJB2 gene mutations that cause 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 the GJB2 gene in each cell are altered. GJB2 gene mutations probably alter gap junctions, which may disturb the level of potassium ions in the inner ear. Levels of potassium ions that are too high may affect the function and survival of cells that are needed for hearing.
Some mutations delete or insert DNA building blocks (base pairs) within or near the GJB2 gene. The most common mutation, particularly in the Caucasian (white) population, deletes one base pair between positions 30 and 35 in the GJB2 gene (written as 35delG or 30delG). In Asian populations, a frequently reported mutation deletes a base pair at position 235 (235delC). Among people with an eastern European (Ashkenazi) Jewish ancestry, a base-pair deletion at position 167 (167delT) is a common mutation. These deletions lead to an abnormally small protein that cannot form functional gap junctions.
Other GJB2 gene mutations replace one of the amino acids used to make connexin 26 with an incorrect amino acid. These mutations lead to an unstable or misshapen protein that cannot form gap junctions, or an altered protein that forms dysfunctional gap junctions.
Researchers have also identified several GJB2 gene mutations that cause another form of nonsyndromic deafness called DFNA3, which is inherited in an autosomal dominant manner. This type of inheritance means that one copy of the GJB2 gene in each cell is altered. These mutations replace one amino acid in connexin 26 with an incorrect amino acid. It remains unclear how these GJB2 gene mutations lead to DFNA3-associated hearing loss. The altered connexin 26 protein probably inhibits the assembly of gap junctions or their normal function, which could disrupt the conversion of sound waves to nerve impulses.
At least nine GJB2 gene mutations have been identified in people with palmoplantar keratoderma with deafness, a condition characterized by hearing loss and unusually thick skin on the palms of the hands and soles of the feet. The GJB2 gene mutations that cause palmoplantar keratoderma with deafness change single amino acids in connexin 26. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses.
At least three GJB2 gene mutations have been identified in people with Vohwinkel syndrome. This condition is characterized by hearing loss and skin abnormalities. In addition to abnormal patches of skin, affected individuals develop tight bands of abnormal fibrous tissue around their fingers and toes that may cut off the circulation to the digits and result in spontaneous amputation. The GJB2 gene mutations that cause Vohwinkel syndrome change single amino acids in connexin 26. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses.
Cytogenetic Location: 13q11-q12
Molecular Location on chromosome 13: base pairs 20,187,462 to 20,192,974
The GJB2 gene is located on the long (q) arm of chromosome 13 between positions 11 and 12.
More precisely, the GJB2 gene is located from base pair 20,187,462 to base pair 20,192,974 on chromosome 13.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about GJB2 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; amino acid ; asparagine ; aspartic acid ; autosomal ; autosomal dominant ; autosomal recessive ; base pair ; cell ; channel ; cochlea ; connexin ; cornea ; deletion ; DNA ; epidermis ; gap junctions ; gene ; glycine ; ichthyosis ; inflammation ; inheritance ; inherited ; ions ; keratitis ; keratoderma ; leukonychia ; lysine ; mutation ; palmoplantar keratoderma ; population ; potassium ; protein ; recessive ; serine ; spontaneous ; syndrome ; tissue
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
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.