2.1. Bartter syndrome

Several people with Bartter syndrome have had mutations in both the CLCNKA gene and a closely related gene called CLCNKB. The CLCNKB gene provides instructions for making a very similar chloride channel, ClC-Kb, that is also found in the kidneys and inner ear. A combination of CLCNKA and CLCNKB gene mutations causes a life-threatening form of the disorder called Bartter syndrome type IV. This condition is also known as antenatal Bartter syndrome with sensorineural deafness because affected individuals have hearing loss caused by abnormalities in the inner ear.

Mutations in the CLCNKA and CLCNKB genes prevent the ClC-Ka and ClC-Kb channels from transporting chloride ions in the kidneys. As a result, the kidneys cannot reabsorb salt normally and excess salt is lost through the urine (salt wasting). The abnormal salt loss disrupts the normal balance of ions in the body. This imbalance underlies many of the major features of Bartter syndrome, including a failure to grow and gain weight at the expected rate (failure to thrive), dehydration, constipation, and increased urine production (polyuria). A loss of ClC-Ka and ClC-Kb function in the inner ear is responsible for the hearing loss characteristic of Bartter syndrome type IV.

2.2. Other Disorders

Studies suggest that several normal variants (polymorphisms) in the CLCNKA gene may be associated with salt-sensitive hypertension, a form of high blood pressure related to increased levels of salt in the blood. However, this association between CLCNKA polymorphisms and hypertension has not been confirmed. Changes in the CLCNKA gene may affect blood pressure by altering the kidneys' ability to reabsorb salt into the bloodstream.