Brugada syndrome More than 300 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 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. familial dilated cardiomyopathy Genetics Home Reference provides information about familial dilated cardiomyopathy. 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 protein building blocks (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 causes heart block. Death of these impaired cardiac cells over time can lead to a buildup of scar tissue (fibrosis), worsening the heart block. Romano-Ward syndrome More than 200 mutations in the SCN5A gene are known to cause Romano-Ward syndrome, often called long QT syndrome. This condition causes the cardiac muscle to take longer than usual to recharge between beats, which can lead to arrhythmia. 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 fainting (syncope) or sudden death. sick sinus syndrome At least 10 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. other disorders 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.

     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 produced from the SCN5A gene are abundant in heart (cardiac) muscle 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.

The following transcription factors affect gene expression:

• NF-kappaB
• GR
• Egr-1
• AhR
• NF-kappaB1

Tissue specificity:

Found in jejunal circular smooth muscle cells (at protein level). Expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. Isoform 4 is expressed in brain.

Molecular Function:

• Voltage-Gated Sodium Channel Activity
• Calmodulin Binding
• Fibroblast Growth Factor Binding
• Enzyme Binding
• Protein Kinase Binding
• Protein Domain Specific Binding
• Ankyrin Binding
• Ubiquitin Protein Ligase Binding
• Ion Channel Binding
• Nitric-Oxide Synthase Binding
• Voltage-Gated Sodium Channel Activity Involved In Cardiac Muscle Cell Action Potential
• Voltage-Gated Sodium Channel Activity Involved In Av Node Cell Action Potential
• Voltage-Gated Sodium Channel Activity Involved In Bundle Of His Cell Action Potential
• Voltage-Gated Sodium Channel Activity Involved In Purkinje Myocyte Action Potential
• Voltage-Gated Sodium Channel Activity Involved In Sa Node Cell Action Potential
• Scaffold Protein Binding

Biological Processes:

• Regulation Of Heart Rate
• Cardiac Ventricle Development
• Brainstem Development
• Sodium Ion Transport
• Positive Regulation Of Sodium Ion Transport
• Response To Denervation Involved In Regulation Of Muscle Adaptation
• Neuronal Action Potential
• Telencephalon Development
• Cerebellum Development
• Sodium Ion Transmembrane Transport
• Odontogenesis Of Dentin-Containing Tooth
• Positive Regulation Of Action Potential
• Positive Regulation Of Epithelial Cell Proliferation
• Membrane Depolarization
• Cardiac Muscle Contraction
• Regulation Of Ventricular Cardiac Muscle Cell Membrane Repolarization
• Regulation Of Atrial Cardiac Muscle Cell Membrane Depolarization
• Regulation Of Atrial Cardiac Muscle Cell Membrane Repolarization
• Regulation Of Ventricular Cardiac Muscle Cell Membrane Depolarization
• Cardiac Conduction
• Cellular Response To Calcium Ion
• Cardiac Muscle Cell Action Potential Involved In Contraction
• Regulation Of Cardiac Muscle Cell Contraction
• Ventricular Cardiac Muscle Cell Action Potential
• Membrane Depolarization During Action Potential
• Membrane Depolarization During Cardiac Muscle Cell Action Potential
• Sa Node Cell Action Potential
• Av Node Cell Action Potential
• Bundle Of His Cell Action Potential
• Membrane Depolarization During Av Node Cell Action Potential
• Membrane Depolarization During Sa Node Cell Action Potential
• Membrane Depolarization During Purkinje Myocyte Cell Action Potential
• Membrane Depolarization During Bundle Of His Cell Action Potential
• Av Node Cell To Bundle Of His Cell Communication
• Regulation Of Heart Rate By Cardiac Conduction
• Regulation Of Sodium Ion Transmembrane Transport

Drug Bank:

• Cinchocaine
• Quinidine Barbiturate
• Benzonatate
• Carbamazepine
• Cocaine
• Disopyramide
• Encainide
• Ethotoin
• Fosphenytoin
• Hexylcaine
• Indecainide
• Lidocaine
• Mexiletine
• Oxcarbazepine
• Phenytoin
• Prilocaine
• Procainamide
• Propafenone
• Ranolazine
• Riluzole
• Tocainide
• Valproic Acid
• Verapamil
• Ajmaline
• Aprindine
• Flecainide
• Moricizine
• Quinidine
• Zonisamide