To illustrate, the TRPC6 GOF mutation identified in patients with focal segmental glomerulosclerosis (FSGS) impairs the function of the inhibitory CBS1 in the cytoplasmic region of TRPC6, yet does not affect the function of the activating The sustained activation of the mutant channel in the presence of Ca2+influx through positive feedback, resulting from the activation of CBS3, leads to an overload of Ca2+ ions in renal pedunculated cells. The gene discussed is MSRB2; the disease is focal segmental glomerulosclerosis.