SCN5A

About SCN5A

SCN5A on chromosome 3p22.2 encodes the alpha subunit of the cardiac sodium channel Nav1.5, which carries the inward sodium current responsible for the rapid upstroke, phase 0, of the cardiac action potential. Variants cause several inherited arrhythmia syndromes. Loss of function variants are the best known genetic cause of Brugada syndrome, found in a minority of cases, which is characterized by a distinctive coved ST segment elevation in the right precordial ECG leads and a risk of ventricular fibrillation and sudden death, and which is more common in men and in Southeast Asia. Loss of function variants also cause progressive cardiac conduction disease, sick sinus syndrome, and some cases of dilated cardiomyopathy. Gain of function variants that produce a persistent late sodium current cause long QT syndrome type 3, in which dangerous arrhythmias tend to occur at rest or during sleep. Some variants produce overlap syndromes combining features of these conditions. Management may involve beta blockers, sodium channel blocking drugs, avoidance of certain medications, and implantable cardioverter defibrillators. SCN5A is also relevant to drug safety, since many medications affect sodium channel function.