Table 1.

Genes associated with GA/AMD

Gene	Protein	Activity	Impact of mutation/polymorphism on protein product function	Mutation impact on complement activity	GA risk
CFH	Factor H (FH)	Cofactor for FI-mediated cleavage of C3b; Competes C1q binding; Competes FHR1	Decrease surface binding of FH decreases FI cleavage; allows C1q binding	Increase	Increase OR = 2.7–7.4
CFHR1/3	FHR1 and / or FHR3	Stabilizers C3b; enhances C1q binding; Competes FH	Gentic deletion allows more FH binding, greater FI cleavage of C3b, less C1q binding	Decrease	Decrease OR = 0.35
CFI	Factor I (FI)	Cleaves C3b to inhibit cascade activity and to produce Ic3b for opsonization/phagocytosis	Reduced FI levels / activity	Increase	Increase OR up to 22
C2	C2	Drives classical / lectin activation of C3	Uncharacterized	Increase	Decrease OR = 0.47–0.49
CFB	Factor B (FB)	Drives alternative / AP amplification via activation of C3	Decrease activity	Decrease	Decrease OR = 0.41–0.54
C3	C3	Activation leads to C3b as opsonin and plateform for AP amplification or C5 cleavage	Resistance to inactivation by FI cleavage	Increase	Increase OR 2.8
C9	C9	Component of membrane attack complex(MAC)	Increased MAC polymerization	Increase	Increase OR 2.2

Reference for Table 1: CFH: 23, 37, 38, 41–44; CFHR1/3: 32, 39, 45–48; FI: 35, 49, 50, 54; C2/CFB: 51, 52, 53, 55-57; C3: 35; C9: 58