SCNN1G gene

The SCNN1G gene provides instructions for creating the gamma subunit of the epithelial sodium channel (ENaC), which is essential for regulating sodium and fluid balance in the body.

Normal Function

The SCNN1G gene provides instructions for making one piece, the gamma 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 open in response to signals that sodium levels in the blood are too low, which allows sodium to flow into cells. From the kidney cells, this sodium is returned to the bloodstream (a process called reabsorption) rather than being removed from the body in urine. 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.

Health Conditions Related to Genetic Changes

Liddle syndrome

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 lead to the production of an abnormally short gamma subunit protein.
• These changes affect a region involved in signaling for the protein's breakdown (degradation).
• Because the protein is not degraded, more ENaC channels remain at the cell surface.
• The increase in channels allows for the reabsorption of excess sodium and water, leading to hypertension and hypokalemia.

Pseudohypoaldosteronism type 1

Mutations in the SCNN1G gene are involved in pseudohypoaldosteronism type 1 (PHA1), a condition typically beginning in infancy. It is characterized by low levels of sodium (hyponatremia), high levels of potassium (hyperkalemia), and severe dehydration due to the loss of excess sodium and fluid in urine.

• SCNN1G mutations are specifically involved in autosomal recessive PHA1, a severe form that does not improve with age.
• Most mutations lead to an abnormally short gamma subunit protein, resulting in reduced or absent ENaC channel activity.
• Impaired sodium reabsorption leads to hyponatremia.
• Reduced function of ENaC channels in lung epithelial cells leads to excess fluid in the lungs and recurrent lung infections.

Other disorders

Some people with cystic fibrosis-like syndrome (also known as atypical cystic fibrosis or bronchiectasis with or without elevated sweat chloride type 3) have a mutation or a normal gene variation (polymorphism) in the SCNN1G gene. These individuals exhibit breathing problems and lung infections similar to cystic fibrosis, even when changes in the CFTR gene are not present. It is thought that these SCNN1G variations disrupt sodium transport and fluid balance.

Other Names for This Gene

• amiloride-sensitive epithelial sodium channel gamma subunit
• amiloride-sensitive sodium channel gamma-subunit
• amiloride-sensitive sodium channel subunit gamma
• BESC3
• ENaC gamma subunit
• ENaCg
• ENaCgamma
• epithelial Na(+) channel subunit gamma
• gamma-ENaC
• gamma-NaCH
• nonvoltage-gated sodium channel 1 subunit gamma
• SCNEG
• SCNNG_HUMAN
• sodium channel, non voltage gated 1 gamma subunit
• sodium channel, non-voltage-gated 1, gamma subunit
• sodium channel, nonvoltage-gated 1, gamma