The association of protection with the absence of CFHR3-CFHR1 is due to enhanced local complement regulation; greater than two copies of CFHR3-CFHR1 increase circulating FHR-1, decrease FH regulation, and explain how copy numbers of CFHR3-CFHR1 act as a pathogenic factor in development of C3G and potentially other complement-mediated diseases (Figure 7). This evidence concerns the gene CFHR3 and complement 3 glomerulopathy.