From: Complement regulator CD46: genetic variants and disease associations
Mutation# | Domain | Disease association | Functional studies | Notes | References |
---|---|---|---|---|---|
−366A > G | Promoter | Systemic sclerosis | Reduced expression | Polymorphic variant; rs2796268 | [56] |
−652A > G | Promoter | Systemic sclerosis | Reduced expression | Polymorphic variant; rs2796267 | [56] |
S13F | SP | HELLP; SLE; aHUS | ND | Â | |
R59X | CCP1 | aHUS and common variable immunodeficiency | Reduced expression | Homozygote | |
K66N | CCP1 | PE & SLE | Normal expression; reduced ability to regulate C4b | Dimerization site on structural model | [59] |
c.475 + 1G > A | CCP2 | TTP | Reduced expression | Splice-site single nucleotide variant; deletes G152-C157 | [81] |
P193S | CCP3 (indel) | Miscarriage | Normal expression & C3b/C4b regulatory activity | Â | [60] |
N213I | CCP3 | Miscarriage | Reduced expression & C3b/C4b regulatory activity | Â | [60] |
V215M | CCP3 | Glomerulonephritis | Expression normal | Patient also has A353V mutation | [62] |
A219V | CCP3 | SLE | ND | Â | [57] |
P324L | STP-C | Miscarriage | Reduced expression; Normal C3b/C4b regulatory activity | Â | [60] |
A353V | TM | Miscarriage; C3-glomerulonephritis; HELLP Syndrome; aHUS | Reduced complement control on cell surface | Â | |
T383I | CYT-1 | Miscarriage; aHUS | Normal expression & C3b/C4b regulatory activity; but could disrupt phosphorylation site on tail | Â |