High-throughput discovery of trafficking-deficient variants in the cardiac potassium channel KV11.1

KCHN2 encodes the KV11.1 potassium channel responsible for IKr, a major repolarization current during the cardiomyocyte action potential. Variants in KCNH2 that lead to decreased IKr have been associated with Type 2 Long QT syndrome (LQT2). The mechanism of LQT2 is most often induced loss of KV11.1 trafficking to the cell surface. Accurately discriminating between variants with normal and abnormal trafficking would aid in understanding the deleterious nature of these variants; however, the volume of reported nonsynonymous KCNH2 variants precludes the use of conventional methods for functional study.

Source: Heart Rhythm - June 4, 2020 Category: Cardiology Authors: Krystian A. Kozek, Andrew M. Glazer, Chai-Ann Ng, Daniel Blackwell, Christian L. Egly, Loren R. Vanags, Marcia Blair, Devyn Mitchell, Kenneth A. Matreyek, Douglas M. Fowler, Bjorn C. Knollmann, Jamie I. Vandenberg, Dan M. Roden, Brett M. Kroncke Source Type: research