Biallelic loss-of-function variants in KCNJ16 presenting with hypokalemic metabolic acidosis
Bryn D. Webb, Hilary Hotchkiss, Pankaj Prasun, Bruce D. Gelb, Lisa M. Satlin
Abstract
Abstract KCNJ16 encodes K ir 5.1 and acts in combination with K ir 4.1, encoded by KCNJ10 , to form an inwardly rectifying K + channel expressed at the basolateral membrane of epithelial cells in the distal nephron. This K ir 4.1/K ir 5.1 channel is critical for controlling basolateral membrane potential and K + recycling, the latter coupled to Na-K-ATPase activity, which determines renal Na + handling. Previous work has shown that Kcnj16 −/− mice and SS Kcnj16 −/− rats demonstrate hypokalemic, hyperchloremic metabolic acidosis. Here, we present the first report of a patient identified to have biallelic loss-of-function variants in KCNJ16 by whole exome sequencing who presented with chronic metabolic acidosis with exacerbations triggered by minor infections.