Rare coding variants induced a change in the C3b binding capacity of the CFHR5 protein. Compared with CFHR5-WT, CFHR5-M (c.508G>A/p.Val170Met), CFHR5-S (c.533A>G/p.Asn178Ser), and CFHR5-D (c.822A>T/p.Glu274Asp) showed significantly higher binding capacities for C3b (CFHR5-M: 109.67%±3.54%; P=0.02; CFHR5-S: 174.27%±9.78%; P<0.001; CFHR5-D: 127.25%±1.75%; P<0.001), whereas CFHR5-Short (c.776T>A/p.Leu259Termination) had a significantly lower C3b binding capacity (CFHR5-Short: 56.89%±0.57%; P<0.001). Experiments were performed in triplicate and repeated three times with similar results. White columns represent quantities of recombinant CFHR5 proteins coated on the plates. Black columns represent C3b binding capacity of the coated CFHR5 proteins compared with wild-type CFHR5. Blank-1, no CFHR5 + C3b + polyclonal anti–C3c/CFHR5 antibody; blank-2, no CFHR5 + no C3b + polyclonal anti–C3c/CFHR5 antibody.