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Table 4 AP complement variants

From: AMD and the alternative complement pathway: genetics and functional implications

Gene Variant Position OR Common/Rare Domain Variant domain effect Effect on AP Ref
C3 R102G 19:6718387 1.7–2.6 Common Macroglobulin 1 Decreased binding efficiency of C3b to its inhibitor CFH decreasing CFH’s cofactor activity Increased AP [20, 65]
C3 P314L 19:6713262 1.5 Common Macroglobulin 3 Decreased binding efficiency of C3b to its inhibitor CFH decreasing CFH’s cofactor activity Increased AP [65]
C3 K155Q 19:6718146 2.8–3.8 Rare Macroglobulin 2 Reduces binding to FH and C3b proteolytic cleavage by CFI Increase C3 convertase production [59, 65]
CFB R32Q 6:31914180 0.32 Common Ba Reduced affinity for C3b and reduced hemolytic activity Decrease formation of C3 convertase; reduced AP [130]
CFB L9H 6:31914024 0.37 Common Signal peptide Affects secretion of CFB Decrease formation of C3 convertase; reduced AP [12]
CFH Y402H 1:196659291 2.45–5.57 Common Complement control protein 7 Affects binding to GAG heparin sulfate, sialic acid, and C-reactive protein Reduces ability of CFH to degrade C3: increased AP [131]
CFH R1210C 1:196716375 23.11 Rare Complement control protein 20 Defective binding to C3b, C3d, and heparin Impaired CFH attachment to host surfaces; reduces AP regulation [58]
CFH R53C 1:196642206   Rare Complement control protein 1 Reduced accelerating activity for AP C3 convertase Altered CFH-mediated cofactor activity or decay-accelerating activity; increased AP [63]
CFH D90G 1:196643011   Rare Complement control protein 2 Alters CFI cofactor activity Decreased cofactor-mediated inactivation; increased AP [63]
CFH I62V 1:196642233 1.95–2.79 Common Complement control protein 2 Binds more efficiently to C3b Enhanced cofactor activity and increased formation of iC3b; reduced AP [63]
CFH N1050Y 1:196712596 0.4 Common Complement control protein 18 Possibly affects GAG and sialic acid binding Increased AP [62]
CFHR1/3 CFHR1/3del   0.29 Common n/a n/a Reduces cofactor activity for CFI and inhibits C5 convertase; reduced AP [13] [132135]
CFI G119R 4:110685820 22.2 Rare Scavenger receptor cysteine-rich Perturbs interdomain packing and stability of CFI Diminished ability to degrade C3b; increased formation of C5 convertase; increased AP [19]
CFI G188A 4:110682768   Rare Scavenger receptor cysteine-rich Perturbs interdomain packing and stability of CFI Diminished ability to degrade C3b; increased formation of C5 convertase; increased AP [19]
C9 P167S 5:39331894 2.2 Rare Membrane attack complex/perforin Alters oligomerization and possibly inhibits C9's lytic activity Affects binding with CD59; alters pore formation [59]
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