KCNQ4 Gene

Definition: Potassium voltage-gated channel, KQT-like subfamily, member 4

Official Symbol:KCNQ4

 Chromosome:1

 Location : 1p34

Gene Size: 54677 bp (41022271..41076947)


No Exons:14


Description:

The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene,Potassium channels made with the KCNQ4 protein are found in the inner ear and along part of the nerve pathway from the ear to the brain (auditory pathway). KCNQ4 potassium channels are also found in small numbers in the heart and some muscles.

Disease :

Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene.

Nonsyndromic deafness - caused by mutations in the KCNQ4 gene

    Several KCNQ4 mutations have been reported in individuals with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA2. Most KCNQ4 mutations change one of the building blocks (amino acids) used to make the KCNQ4 protein. Nearly all of these changes affect the region of the protein that forms the pore or channel opening. As a result, the channel does not function properly and normal potassium ion levels may be disturbed. Two mutations delete part of the KCNQ4 gene, which results in an abnormally small KCNQ4 protein that cannot form functional channels. It is unclear whether deafness results from disturbed potassium levels within the inner ear, alterations in the auditory pathway, or both.

GJB3 Gene

Definition:Gap junction protein, beta 3, 31kDa.

Official Symbol:GJB3

 Chromosome:1

 Location : 1p34

Gene Size:  5178 bp (35,019,377 to 35,024,554)


No Exons:

Description:

Gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell.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.

Disease :

Mutations in this gene can cause non-syndromic deafness or erythrokeratodermia variabilis, a skin disorder. Alternative splicing results in multiple transcript variants encoding the same protein.

nonsyndromic deafness

    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.