Using in vitro translated podocin and purified nephrin, it was found that nephrin bound poorly to R229Q podocin; these data suggest that the R229Q mutation alone is, probably, insufficient to cause FSGS but it might enhance susceptibly to renal injury in association with a second NPHS2 mutation or variants in other genes, such as nephrin. This evidence concerns the gene NPHS1 and focal segmental glomerulosclerosis.