Biallelic loss-of-function variants in KCNJ16 presenting with hypokalemic metabolic acidosis

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.