SCNN1A

The SCNN1A gene provides instructions for making one piece, the alpha subunit, of a protein complex called the epithelial sodium channel (ENaC). The channel is composed of alpha, beta, and gamma subunits, each of which is produced from a different gene. These channels are found at the surface of certain cells called epithelial cells in many tissues of the body, including the kidneys, lungs, and sweat glands. The ENaC channel transports sodium into cells.

In the kidney, ENaC channels take sodium into cells in response to signals that sodium levels in the body are too low. From the kidney cells, this sodium is returned to the bloodstream rather than being removed from the body (a process called reabsorption). In addition to regulating the amount of sodium in the body, the flow of sodium ions helps control the movement of water in tissues. For example, ENaC channels in lung cells help regulate the amount of fluid in the lungs.

pseudohypoaldosteronism type 1 - caused by mutations in the SCNN1A gene

At least a dozen mutations in the SCNN1A gene cause 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. In particular, SCNN1A gene mutations are involved in autosomal recessive PHA1, a severe form of the condition that does not improve with age.

Most mutations in the SCNN1A gene result in a shortened alpha subunit protein of the ENaC channel. Other mutations delete a small piece of DNA or change a single protein building block (amino acid) in the alpha subunit protein. SCNN1A gene mutations lead to 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.

other disorders - associated with the SCNN1A gene

Some people with cystic fibrosis-like syndrome have a mutation or a normal gene variation (polymorphism) in the SCNN1A gene. People with cystic fibrosis-like syndrome (also known as atypical cystic fibrosis or bronchiectasis with or without elevated sweat chloride type 2) 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 SCNN1A gene can disrupt sodium transport and fluid balance, which leads to the signs and symptoms of cystic fibrosis-like syndrome.