Check out our October newsletter
KCNJ8 (NM_004982.2) encodes Kir6.1, a pore-forming member of the inward rectifier potassium channel family. Kir6.1 plays an important role in the ventricular repolarization. KCNJ8 is located at 12p12.1 and is composed of 3 exons. KCNJ8 mutations are typically inherited in an autosomal dominant manner with reduced penetrance and variable expressivity. A frameshift and missense variant in the KCNJ8 gene have been reported in infants with sudden infant death syndrome. Further functional studies indicate these changes cause loss of function of the Kir6.1 protein (Tester D et al. Circ Cardiovas Genet. 2011;4:510-515). A missense gain of function alteration, p.S422L, has been shown to be associated with J-wave syndromes, including atrial fibrillation and Brugada syndrome (BrS) (Barajas-Martinez et al. Heart Rhythm. 2012 Apr;9(4):548-55. Epub 2011 Nov 3). Two additional missense alterations, one of which was characterized as a gain of function, have been reported in association with Cantú syndrome (Brownstein C et al. Eur J Med Genet. 2013; 56(12):678-682; Cooper P et al. Hum Mutat. 2014;35:809-813).