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
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.More About This Health Condition
Pseudohypoaldosteronism type 1
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.More About This Health Condition
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.
Other Names for This Gene
- amiloride-sensitive epithelial sodium channel gamma subunit
- amiloride-sensitive sodium channel gamma-subunit
- amiloride-sensitive sodium channel subunit gamma
- ENaC gamma subunit
- epithelial Na(+) channel subunit gamma
- nonvoltage-gated sodium channel 1 subunit gamma
- sodium channel, non voltage gated 1 gamma subunit
- sodium channel, non-voltage-gated 1, gamma subunit
- sodium channel, nonvoltage-gated 1, gamma
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
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- Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger JD, Rossier BC. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994 Feb 3;367(6462):463-7. Citation on PubMed
- Chang SS, Grunder S, Hanukoglu A, Rösler A, Mathew PM, Hanukoglu I, Schild L, Lu Y, Shimkets RA, Nelson-Williams C, Rossier BC, Lifton RP. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996 Mar;12(3):248-53. Citation on PubMed
- Chen SY, Bhargava A, Mastroberardino L, Meijer OC, Wang J, Buse P, Firestone GL, Verrey F, Pearce D. Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2514-9. Citation on PubMed or Free article on PubMed Central
- Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP. Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995 Sep;11(1):76-82. Citation on PubMed
- Masilamani S, Kim GH, Mitchell C, Wade JB, Knepper MA. Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney. J Clin Invest. 1999 Oct;104(7):R19-23. Citation on PubMed or Free article on PubMed Central
- Mutesa L, Azad AK, Verhaeghe C, Segers K, Vanbellinghen JF, Ngendahayo L, Rusingiza EK, Mutwa PR, Rulisa S, Koulischer L, Cassiman JJ, Cuppens H, Bours V. Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants. Chest. 2009 May;135(5):1233-1242. doi: 10.1378/chest.08-2246. Epub 2008 Nov 18. Citation on PubMed
- Snyder PM, Price MP, McDonald FJ, Adams CM, Volk KA, Zeiher BG, Stokes JB, Welsh MJ. Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel. Cell. 1995 Dec 15;83(6):969-78. Citation on PubMed
- Warnock DG. Liddle syndrome: genetics and mechanisms of Na+ channel defects. Am J Med Sci. 2001 Dec;322(6):302-7. Review. Citation on PubMed