Complement regulator CD46: genetic variants and disease associations

Table 2 CD46 mutations associated with aHUS and/or other diseases

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		[57, 58, 70]
R59X	CCP1	aHUS and common variable immunodeficiency	Reduced expression	Homozygote	[36, 37]
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		[60]
N213I	CCP3	Miscarriage	Reduced expression & C3b/C4b regulatory activity		[60]
V215M	CCP3	Glomerulonephritis	Expression normal	Patient also has A353V mutation	[62]
A219V	CCP3	SLE	ND		[57]
P324L	STP-C	Miscarriage	Reduced expression; Normal C3b/C4b regulatory activity		[60]
A353V	TM	Miscarriage; C3-glomerulonephritis; HELLP Syndrome; aHUS	Reduced complement control on cell surface		[47, 48, 60, 64]
T383I	CYT-1	Miscarriage; aHUS	Normal expression & C3b/C4b regulatory activity; but could disrupt phosphorylation site on tail		[60, 69]

Abbreviations: See Table 1 abbreviations, SLE systemic lupus erythematosus, PE preeclampsia, TTP thrombotic thrombocytopenic purpura, HELLP syndrome, hemolysis, elevated liver enzymes and low platelets

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