GJB3

The GJB3 gene provides instructions for making a protein called gap junction beta 3, more commonly known as connexin 31. Connexin 31 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.

Connexin 31 is found in several different tissues throughout the body, including the skin, the inner ear, and the nerve that connects the inner ear with the brain (the auditory nerve). Connexin 31 plays a role in the growth and maturation of the outermost layer of skin (the epidermis). The presence of this protein in the inner ear and auditory nerve suggests that it may be involved in hearing. Hearing requires the conversion of sound waves to electrical nerve impulses, which travel along the auditory nerve to the brain. The exact role of connexin 31 in the inner ear and auditory nerve is unclear.

nonsyndromic deafness - associated with the GJB3 gene

Researchers have identified a few GJB3 mutations in people with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA2. DFNA2 deafness is inherited in an autosomal dominant manner, which means that one copy of the GJB3 gene in each cell is altered. A few GJB3 mutations have also been identified in people with autosomal recessive nonsyndromic deafness. This type of inheritance means that two copies of the GJB3 gene in each cell are altered. It is unclear, however, whether GJB3 mutations are the direct cause of hearing loss in individuals with either of these types of deafness.

GJB3 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, and other mutations replace one amino acid with an incorrect amino acid. These changes likely alter the 3-dimensional shape or size of connexin 31, which could disrupt the assembly or function of gap junctions. It is unclear how GJB3 mutations contribute to hearing loss.

other disorders - caused by mutations in the GJB3 gene

Several GJB3 mutations have been identified in people with erythrokeratodermia variabilis (EKV), a skin disorder characterized by areas of abnormally thickened skin and temporarily reddened patches. These mutations replace one of the protein building blocks (amino acids) used to make connexin 31 with an incorrect amino acid. The altered protein probably interferes with the assembly of gap junctions, or it disturbs the normal function of the gap junction by leaving the channel continuously open. It is unclear how GJB3 mutations disrupt the growth and maturation of skin cells and cause erythrokeratodermia variabilis.