APOL1 genotyping is incomplete without testing for the protective M1 modifier p.N264K variant

Focal segmental glomerulosclerosis (FSGS), a pattern of injury seen in some patients with nephrotic syndrome, is a leading cause of chronic kidney disease (CKD) especially in people of African ancestry [1].In 2008, using the method of Mapping by Admixture Linkage Disequilibrium (MALD), two studies discovered a locus on chromosome 22 as the genetic driver of high prevalence of hypertension associated end stage kidney disease (H-ESKD) and FSGS in African Americans [2,3].Fine mapping of the region later showed that two variants in apolipoprotein L1(APOL1), G1 (rs73885319: p.S342G and rs60910145: p.I384M) and G2 (rs71785313: a 6 base-pair deletion), when inherited in homozygous or compound heterozygous pattern, are driving this major risk [4,5].APOL1 is