ABSTRACT: Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital bilateral sensorineural hearing loss, a prolonged QT interval (QTc) on an electrocardiogram (ECG), and a high incidence of sudden death in childhood. More than 90% of JLNS cases are associated with variants in the potassium voltage-gated channel subfamily Q member 1 gene, KCNQ1 (Kv7.1). Herein, eighteen identified JLNS-related KCNQ1 variants were examined, including I145S, Y148S, G168R, Y171X, S182R, G186D, R190Q, G269D, G272D, A302V, G306V, V307V, S333F, A344A, F351L, K422S, T587M, and R594Q. Using an integrative method, we systematically characterized the biophysical properties, functional, and membrane trafficking of KCNQ1 variants distributed in different structural domains of the channel. The results demonstrated
