Diseases caused by mutations in Nav1.5 interacting proteins.
Sodium current in the heart flows principally through the pore protein NaV1.5, which is part of a complex of interacting proteins that serve both to target and localize the complex in the membrane, and to modulate function by such post-translational modifications as phosphorylation and nitrosylation. Multiple mutations in seven different NaV1.5 interacting proteins have been associated with dysfunctional sodium current and inherited cardiac diseases, including long QT syndrome, Brugada syndrome, atrial fibrillation, and cardiomyopathy, as well as sudden infant death syndrome (SIDS). Mutations in as yet unidentified interacting proteins may account for cardiac disease for which a genetic basis has not yet been established. Characterizing the mechanisms by which these mutations cause disease may give insight into etiologies and treatments of more common acquired cardiac disease, such as ischemia and heart failure.
Department of Medicine, Division of Cardiovascular Medicine, University of Wisconsin, Madison, Wisconsin, USA 53792.
John W
JW
Kyle
Department of Medicine, Division of Cardiovascular Medicine, University of Wisconsin, Madison, Wisconsin, USA 53792.
Jonathan C
JC
Makielski
Arrhythmia; Brugada syndrome; Cardiomyopathy; Late Sodium Current; Long QT syndrome; Macromolecular complex; SCN5a; Sodium channel; Sodium current; Sudden Infant Death Syndrome