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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] [132–135]

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]