Prediction of Kv11.1 potassium channel PAS-domain variants trafficking via machine learning

Congenital long QT syndrome (LQTS) is characterized by a prolonged QT-interval on an electrocardiogram (ECG). An abnormal prolongation in the QT-interval increases the risk for fatal arrhythmias. Genetic variants in several different cardiac ion channel genes, including KCNH2, are known to cause LQTS. Here, we evaluated whether structure-based molecular dynamics (MD) simulations and machine learning (ML) could improve the identification of missense variants in LQTS-linked genes. To do this, we investigated KCNH2 missense variants in the Kv11.1 channel protein shown to have wild type (WT) like or class II (trafficking-deficient) phenotypes in vitro.

Source: Journal of Molecular and Cellular Cardiology - May 13, 2023 Category: Cytology Authors: Xuan Fang, Kalyan Immadisetty, Geraldine San Ramon, Cassandra M. Hartle, Thomas P. McCoy, Regeneron Genetics Center, Tooraj Mirshahi, Brian P. Delisle, Peter M. Kekenes-Huskey Source Type: research