The SCN5A gene belongs to a family of genes that provide instructions for making sodium channels. These channels open and close at specific times to control the flow of positively charged sodium atoms (sodium ions) into cells. The sodium channels containing proteins produced from the SCN5A gene are abundant in heart (cardiac) muscle cells and play key roles in these cells' ability to generate and transmit electrical signals. These channels play a major role in signaling the start of each heartbeat, coordinating the contractions of the upper and lower chambers of the heart, and maintaining a normal heart rhythm.
Health Conditions Related to Genetic Changes
More than 400 mutations in the SCN5A gene have been identified in people with Brugada syndrome, which is a heart condition characterized by an irregular heart rhythm (arrhythmia). SCN5A gene mutations also cause sudden unexpected nocturnal death syndrome (SUNDS), which was originally described in Southeast Asian populations. Researchers have since determined that SUNDS and Brugada syndrome are the same disorder.
Some SCN5A gene mutations associated with Brugada syndrome change single protein building blocks (amino acids) in the SCN5A protein. These mutations alter the structure of ion channels made with the SCN5A protein and disrupt the flow of sodium ions into cardiac muscle cells. Other mutations prevent the SCN5A gene from producing any functional ion channels, which also reduces the inward flow of sodium ions. A disruption in ion transport changes the way the heart beats, leading to the arrhythmia often found in Brugada syndrome and SUNDS.More About This Health Condition
Progressive familial heart block
A few mutations in the SCN5A gene have been found to cause progressive familial heart block. This condition alters the normal beating of the heart and can lead to fainting (syncope) or sudden cardiac arrest and death. The SCN5A gene mutations change single amino acids in the SCN5A protein. Channels made with this altered protein allow little or no sodium to enter the cell. Cardiac cells with these altered channels have difficulty producing and transmitting electrical signals that coordinate normal heartbeats. Interruption of this signaling is known as heart block. The impaired cardiac cells die, leading to a buildup of scar tissue (fibrosis) over time that worsens the heart block.More About This Health Condition
At least 238 mutations in the SCN5A gene are known to cause Romano-Ward syndrome, which is the most common form of an arrhythmia called long QT syndrome. Mutations in this gene account for five to 10 percent of cases of Romano-Ward syndrome. In individuals with this condition the cardiac muscle takes longer than usual to recharge between beats.
The SCN5A gene mutations that cause Romano-Ward syndrome include changes in single amino acids and deletions or insertions of a small number of amino acids in the SCN5A protein. Channels made with these altered SCN5A proteins stay open longer than usual, which allows sodium ions to continue flowing into cardiac muscle cells abnormally. This delay in channel closure alters the transmission of electrical signals in the heart, increasing the risk of an irregular heartbeat that can cause syncope or sudden death.More About This Health Condition
Sick sinus syndrome
At least 16 mutations in the SCN5A gene have been found to cause another heart condition called sick sinus syndrome. This condition affects the function of the sino-atrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SCN5A gene mutations that cause sick sinus syndrome lead to the production of nonfunctional sodium channels or abnormal channels that cannot transport ions properly. The flow of these ions is essential for creating the electrical impulses that start each heartbeat and spread these signals to other areas of the heart. Mutations reduce the flow of sodium ions, which alters the SA node's ability to create and spread electrical signals. These changes increase the risk of abnormally fast or slow heartbeats, which can cause dizziness, light-headedness, syncope, and related symptoms.More About This Health Condition
Familial atrial fibrillation
MedlinePlus Genetics provides information about Familial atrial fibrillationMore About This Health Condition
Familial dilated cardiomyopathy
MedlinePlus Genetics provides information about Familial dilated cardiomyopathyMore About This Health Condition
Left ventricular noncompaction
MedlinePlus Genetics provides information about Left ventricular noncompactionMore About This Health Condition
Variations in the SCN5A gene are associated with several other heart conditions. These include potentially life-threatening forms of arrhythmia called atrial fibrillation and ventricular fibrillation. The genetic variations associated with these conditions alter the flow of sodium ions through the channel, which can lead to abnormal heart rhythms and affect the heart's ability to pump blood.
SCN5A gene mutations have also been identified in some cases of sudden infant death syndrome (SIDS). SIDS is a major cause of death in babies younger than 1 year. It is characterized by sudden and unexplained death, usually during sleep. Researchers are working to determine how changes in the SCN5A gene could contribute to SIDS. Other genetic and environmental factors, many of which have not been identified, also play a part in determining the risk of this disorder.
Certain drugs, including medications used to treat arrhythmias, infections, seizures, and psychotic disorders, can lead to an abnormal heart rhythm in some people. This drug-induced heart condition, which is known as acquired long QT syndrome, increases the risk of cardiac arrest and sudden death. A small percentage of cases of acquired long QT syndrome occur in people who have an underlying change in the SCN5A gene.
Other Names for This Gene
- Sodium channel protein, cardiac muscle alpha-subunit
- sodium channel, voltage gated, type V alpha subunit
- sodium channel, voltage-gated, type V, alpha (long QT syndrome 3)
- sodium channel, voltage-gated, type V, alpha subunit
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
- Brugada P. Brugada syndrome: More than 20 years of scientific excitement. J Cardiol. 2016 Mar;67(3):215-20. doi: 10.1016/j.jjcc.2015.08.009. Epub 2015 Nov 25. Citation on PubMed
- Butters TD, Aslanidi OV, Inada S, Boyett MR, Hancox JC, Lei M, Zhang H. Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome. Circ Res. 2010 Jul 9;107(1):126-37. doi: 10.1161/CIRCRESAHA.110.219949. Epub 2010 May 6. Citation on PubMed or Free article on PubMed Central
- Gui J, Wang T, Jones RP, Trump D, Zimmer T, Lei M. Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome. PLoS One. 2010 Jun 7;5(6):e10985. doi: 10.1371/journal.pone.0010985. Erratum In: PLoS One. 2010;5(6). doi: 10.1371/annotation/1230d58a-8d86-4a5c-8918-0a2c513839be. PLoS One. 2010;5(7) doi: 10.1371/annotation/b8de07e2-fd0a-4ae3-bfe6-0eb565da0f75. Citation on PubMed or Free article on PubMed Central
- Herfst LJ, Rook MB, Jongsma HJ. Trafficking and functional expression of cardiac Na+ channels. J Mol Cell Cardiol. 2004 Feb;36(2):185-93. doi: 10.1016/j.yjmcc.2003.11.014. Citation on PubMed
- Juang JM, Huang SK. Brugada syndrome--an under-recognized electrical disease in patients with sudden cardiac death. Cardiology. 2004;101(4):157-69. doi: 10.1159/000076693. Epub 2004 Feb 12. Citation on PubMed
- Kapplinger JD, Tester DJ, Alders M, Benito B, Berthet M, Brugada J, Brugada P, Fressart V, Guerchicoff A, Harris-Kerr C, Kamakura S, Kyndt F, Koopmann TT, Miyamoto Y, Pfeiffer R, Pollevick GD, Probst V, Zumhagen S, Vatta M, Towbin JA, Shimizu W, Schulze-Bahr E, Antzelevitch C, Salisbury BA, Guicheney P, Wilde AA, Brugada R, Schott JJ, Ackerman MJ. An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 Jan;7(1):33-46. doi: 10.1016/j.hrthm.2009.09.069. Epub 2009 Oct 8. Citation on PubMed or Free article on PubMed Central
- Lei M, Huang CL, Zhang Y. Genetic Na+ channelopathies and sinus node dysfunction. Prog Biophys Mol Biol. 2008 Oct-Nov;98(2-3):171-8. doi: 10.1016/j.pbiomolbio.2008.10.003. Epub 2008 Nov 5. Citation on PubMed
- Paulussen AD, Gilissen RA, Armstrong M, Doevendans PA, Verhasselt P, Smeets HJ, Schulze-Bahr E, Haverkamp W, Breithardt G, Cohen N, Aerssens J. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 Mar;82(3):182-8. doi: 10.1007/s00109-003-0522-z. Epub 2004 Feb 4. Citation on PubMed
- Plant LD, Bowers PN, Liu Q, Morgan T, Zhang T, State MW, Chen W, Kittles RA, Goldstein SA. A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y. J Clin Invest. 2006 Feb;116(2):430-5. doi: 10.1172/JCI25618. Citation on PubMed or Free article on PubMed Central
- Shimizu W, Aiba T, Kamakura S. Mechanisms of disease: current understanding and future challenges in Brugada syndrome. Nat Clin Pract Cardiovasc Med. 2005 Aug;2(8):408-14. doi: 10.1038/ncpcardio0268. Citation on PubMed
- Vatta M, Dumaine R, Varghese G, Richard TA, Shimizu W, Aihara N, Nademanee K, Brugada R, Brugada J, Veerakul G, Li H, Bowles NE, Brugada P, Antzelevitch C, Towbin JA. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet. 2002 Feb 1;11(3):337-45. doi: 10.1093/hmg/11.3.337. Citation on PubMed
- Veerman CC, Wilde AA, Lodder EM. The cardiac sodium channel gene SCN5A and its gene product NaV1.5: Role in physiology and pathophysiology. Gene. 2015 Dec 1;573(2):177-87. doi: 10.1016/j.gene.2015.08.062. Epub 2015 Sep 8. Citation on PubMed
- Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC, Hohnloser SH, Shimizu W, Schwartz PJ, Stanton M, Murray KT, Norris K, George AL Jr, Roden DM. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation. 2002 Apr 23;105(16):1943-8. doi: 10.1161/01.cir.0000014448.19052.4c. Citation on PubMed
- Zaklyazminskaya E, Dzemeshkevich S. The role of mutations in the SCN5A gene in cardiomyopathies. Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1799-805. doi: 10.1016/j.bbamcr.2016.02.014. Epub 2016 Feb 23. Citation on PubMed
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