SCNN1G

At least 5 mutations in the SCNN1G gene can cause a condition known as Liddle syndrome. People with Liddle syndrome have high blood pressure (hypertension) and low levels of potassium in their blood (hypokalemia), often beginning in childhood. Mutations in the SCNN1G gene associated with Liddle syndrome lead to the production of an abnormally short gamma subunit protein. These changes affect an important region of the gamma subunit protein involved in signaling for its breakdown (degradation). As a result of the mutations, the protein is not degraded, and more ENaC channels remain at the cell surface. The increase in channels at the cell surface allows the reabsorption of excess sodium (followed by water), which leads to hypertension. Reabsorption of sodium into the blood is linked with removal of potassium from the blood, so excess sodium reabsorption leads to hypokalemia.

Mutations in the SCNN1G gene are involved in a condition called pseudohypoaldosteronism type 1 (PHA1). This condition typically begins in infancy and is characterized by low levels of sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood, and severe dehydration due to the loss of excess sodium and fluid in urine. In particular, SCNN1G gene mutations are involved in autosomal recessive PHA1, a severe form of the condition that does not improve with age.

Most mutations in the SCNN1G gene lead to an abnormally short gamma subunit protein. These mutations result in reduced or absent ENaC channel activity. As a result, sodium reabsorption is impaired, leading to hyponatremia and other signs and symptoms of autosomal recessive PHA1. The reduced function of ENaC channels in lung epithelial cells leads to excess fluid in the lungs and recurrent lung infections.

Some people with cystic fibrosis-like syndrome have a mutation or a normal gene variation (polymorphism) in the SCNN1G gene. People with cystic fibrosis-like syndrome (also known as atypical cystic fibrosis or bronchiectasis with or without elevated sweat chloride type 3) have signs and symptoms that resemble those of cystic fibrosis, including breathing problems and lung infections. However, changes in the gene most commonly associated with cystic fibrosis, CFTR, cannot explain development of the condition. It is thought that a mutation or gene variation in the SCNN1G gene can disrupt sodium transport and fluid balance, which leads to the signs and symptoms of cystic fibrosis-like syndrome.