Journal Article

The many faces of SCN5A pathogenic variants: from channelopathy to cardiomyopathy

Parcharidou, Despoina, Tziomalos, Georgios, Didagelos, Matthaios, Agbariah, Andrea, Gossios, Thomas D., Kamperidis, Vasileios, Zegkos, Thomas, Efthimiadis, Georgios K., Vouloagkas, Ioannis, Ziakas, Antonios

2025

Overview

The SCN5A gene encodes the alpha subunit of the cardiac sodium channel, which plays a fundamental role in the generation and propagation of the action potential in the heart muscle. During the past years our knowledge concerning the function of the cardiac sodium channel and the diseases caused by mutations of the SCN5A gene has grown. Although initially SCN5A pathogenic variants were mainly associated with channelopathies, increasing recent evidence suggests an association with structural heart disease in the form of heart muscle disease. The pathways leading to a cardiomyopathic phenotype remain unclear and require further elucidation. The aim of the present review is to provide a concise summary regarding the mechanisms through which SCN5A pathogenic variants result in heart disease, focusing in cardiomyopathy, highlighting along the way the complex role of the SCN5A gene at the intersection of cardiac excitability and contraction networks.

• Publisher: Springer US,Springer Nature B.V
• Subject: Action potential / Cardiac arrhythmia / Cardiac muscle / Cardiology / Cardiomyopathies - genetics / Cardiomyopathies - physiopathology / Cardiomyopathy / Cardiovascular disease / Channelopathies - genetics / Channelopathies - physiopathology / Channelopathy / Coronary artery disease / Excitability / Genotype & phenotype / Heart diseases / Heart failure / Hospitals / Humans / Long QT syndrome / Medicine / Medicine & Public Health / Muscle contraction / Mutation / Myocarditis / NAV1.5 Voltage-Gated Sodium Channel - genetics / Phenotype / Phenotypes / Proteins / Review / Sodium