CLCNKB gene
The CLCNKB gene provides instructions for a chloride channel that regulates salt reabsorption in the kidneys and supports normal hearing function in the inner ear.
Normal Function
The CLCNKB gene belongs to the CLC family of genes, which provide instructions for making chloride channels. These channels transport negatively charged chloride ions and play a key role in a cell's ability to generate and transmit electrical signals.
The CLCNKB gene provides instructions for making a chloride channel called ClC-Kb. These channels are found predominantly in the kidneys. ClC-Kb is one of several proteins that work together to regulate the movement of ions into and out of kidney cells. The transport of chloride ions by ClC-Kb channels is part of the mechanism by which the kidneys reabsorb salt (sodium chloride or NaCl) from the urine back into the bloodstream. The retention of salt affects the body's fluid levels and helps maintain blood pressure.
ClC-Kb channels are also located in the inner ear, where they play a role in normal hearing.
Health Conditions Related to Genetic Changes
Bartter syndrome
More than 30 mutations in the CLCNKB gene have been identified in people with Bartter syndrome type III, also described as classical Bartter syndrome. A loss of functional ClC-Kb channels impairs the transport of chloride ions in the kidneys, causing the kidneys to lose excess salt through the urine (salt wasting). This imbalance underlies many of the major features of Bartter syndrome type III.
A combination of CLCNKA and CLCNKB gene mutations causes a life-threatening form of the disorder known as Bartter syndrome type IV or antenatal Bartter syndrome with sensorineural deafness. In addition to salt wasting, this form is characterized by hearing loss resulting from a loss of ClC-Ka and ClC-Kb function in the inner ear.
Gitelman syndrome
Mutations in the CLCNKB gene are a rare cause of Gitelman syndrome. These genetic changes impair the kidneys' ability to reabsorb salt, leading to salt wasting. Abnormalities of salt transport also affect the reabsorption of other ions, including potassium, magnesium, and calcium, leading to the characteristic features of Gitelman syndrome.
Other disorders
A common variation (polymorphism) in the CLCNKB gene, where the amino acid threonine is replaced by serine at position 481 (Thr481Ser or T481S), has been associated with salt-sensitive hypertension. This genetic change increases the activity of the ClC-Kb channel, directing the kidneys to reabsorb more salt into the bloodstream, which raises blood pressure.
Other Names for This Gene
- chloride channel Kb
- chloride channel protein ClC-Kb
- chloride channel, kidney, B
- chloride channel, voltage-sensitive Kb
- ClC-K2
- ClC-Kb
- CLCKB
- CLCKB_HUMAN
- hClC-Kb