Table 1 CD46 mutations associated with aHUS and functional consequences

M1K

SP

Reduced expression

[69]

S13F

SP

ND

[70]

Y29X

SP

ND

Compound heterozygote with factor H mutation

[43, 53]

D33H

SP

ND

[46]

IVS1 − 1G > C

CCP1

Reduced expression

Aberrant splicing of 2 bp after normal splice site; premature stop codon C35X

[36, 43, 47, 48]

IVS2 + 2 T > G

CCP1

Reduced expression

Deleted 144 bp and 48 amino acids in phase with wild-type

[36, 43, 47, 48, 71]

IVS2 + 1G > C

CCP1

Reduced expression

[39, 38, 71, 48, 43]

C35X

CCP1

Reduced expression

[43, 72]

C35Y

CCP1

Reduced expression

[43, 47, 48, 71]

E36X

CCP1

Reduced expression

[43, 71]

P50T

CCP1

ND

[43, 72]

Y54C

CCP1

ND

Successful treatment with eculizumab; transplanted

[73]

R59X

CCP1

Reduced expression

[43, 46, 47, 71, 74]

C64F

CCP1

Reduced expression

Varicella trigger; 16 y/o successfully treated with plasma exchange

[43, 75, 76]

K65D-fsX73

CCP1

ND

[43, 53]

c. 286 + 2 T > G

Between CCP1-2

ND

Frameshift leads to stop in CCP2

[45]

IVS2 − 2A > G

CCP2

Reduced expression

c. 287 − 2A > G;

Lacks exon 3 and creates stop codon at L133X;

[36, 43, 45, 47, 48, 71, 77–79]

C99R

CCP2

Reduced expression

[43, 47, 48]

R103W

CCP2

Normal expression & C3/C4 regulatory activity

[38, 39, 43, 48, 61, 71]

R103Q

CCP2

ND

Compound heterozygote with factor H mutation

[43, 53]

Y117X

CCP2

Reduced expression

[46, 69]

G130V

CCP2

ND

[43, 53]

G135D

CCP2

Reduced expression

[69]

G135V-fsX13

CCP2

ND

[43, 74]

P165S

CCP3

Reduced expression

[38, 39, 43, 48, 53]

E179Q

CCP3

Normal to higher expression; 50 % loss regulatory activity

[36, 43, 48]

D185N/Y189D

CCP3

Reduced expression

[36, 43, 48]

Y189D

CCP3

Reduced expression

[43, 45, 48, 70–72, 80]

G196R

CCP3

Reduced expression; decreased C4b CA only (FI interaction site)

[36, 48, 53, 73, 81]

G204R

CCP3

ND

[43, 53]

S206P

CCP3

ND

[43, 53]

I208Y

CCP3

ND

Compound heterozygote with factor H mutation

[43, 53]

C210F

CCP3

ND

Compound heterozygote with factor-I mutation

[43, 53]

W216C

CCP3

ND

Near functional site per [44]

[43, 45]

P231R

CCP4

ND

Functional site per [44]

[43, 45]

E234K

CCP4

ND

[46]

S240P

CCP4

Normal expression; loss of C3b CA & binding

Originally numbered S206P

[43, 48, 51]

F242C

CCP4

Normal expression; reduced C3b/C4b binding and CA

[43, 45, 48, 53, 72]

Y248X

CCP4

Reduced expression

[43, 48, 52, 71, 72]

Y248C

CCP4

ND

[46]

K249N-fsX5

CCP4

ND

[46]

G259V

CCP4

Reduced expression; reduced C3b/C4b binding and CA

Compound heterozygote with FH mutations

[82]

L262P

CCP4

Reduced expression

aHUS pts successfully treated with eculizumab;

[83]

T267-fs270X

CCP4

Reduced expression

delA843-C844

[43, 48, 52, 72]

Del D271/S272

CCP4

Reduced expression

Originally numbered D237/S238

[43, 48, 51, 84]

c.852-856del

CCP4

Reduced expression

Originally numbered as 903-907del

[38, 39, 43, 48]

858-872del + D277N + P278S

CCP4

Reduced expression

[43, 47, 48]

IVS10 + 2 T > C

TM

Reduced expression

Exon 10 skipped changing aa 316–321 & adding a stop at 322

[43, 71, 74]

c.983-984delAT

TM

ND

Frameshift with stop

[43, 45]

A353V

TM

Normal expression and complement regulatory function

Uncommon variant; numerous studies and several disease implications; sometimes termed A304V

[43, 47, 48, 61]

A359V

TM

ND

Japanese pt; compound heterozygote with Y189D in CCP3

[70]

T383I

CYT-1

ND

Fatal infections triggered aHUS in 2 patients. Mother massive viral infection; son by E. coli O157:H7

[43, 53, 69]