Protein | Gene | Inheritance | Gene OMIM | Laboratory features | Diseases |
Classical pathway | |||||
C1q | C1QA | AR | 120550 | CH50 = 0; CP defective activation; Inefficient clearance apoptotic cells | SLE; infections with encapsulated organisms |
C1QB | AR | 120570 | |||
C1QC | AR | 120575 | |||
C1r | C1R | AR | 613785 | CH50 = 0; CP defective activation | SLE; infections with encapsulated organisms; Ehlers-Danlos phenotype |
C1R | AD GOF | Normal CH50 | Hyperpigmentation; skin fragility | ||
C1s | C1S | AR | 120580 | CH50 = 0; CP defective activation | SLE; infection with encapsulated organisms; Ehlers-Danlos phenotype |
C1S | AD GOF | Normal CH50 | Hyperpigmentation; skin fragility | ||
C2 | C2 | AR | 217000 | CH50 = 0; CP defective activation | SLE; infections with encapsulated organisms; atherosclerosis; AMD |
C4 | C4A + C4B | AR | 120810 + 120820 | CH50 = 0; CP defective activation; biallelic mutations, deletions, or conversions of both C4A and C4B | SLE; infections with encapsulated organisms; partial or complete C4A deficiency predisposes to SLE |
C3* | C3 | AR LOF | 120700 | Both CH50 and AH50 = 0; Defective opsonization and humoral immune response | Infections; glomerulonephritis |
AD GOF | Increased complement activation | aHUS; AMD | |||
Lectin pathway | |||||
MBL | MBL2 | AD | 154545 | LP defective activation | Increased susceptibility to bacterial infection |
MASP-2 | MASP2 | AR | 605102 | LP defective activation | Pyogenic infections; inflammatory lung disease; autoimmunity |
MASP-3 | MASP1¶ | AR | 600521 | LP defective activation | 3MC1 |
Collectin (CL-L1; CL-K1) | COLEC11 | AR | 612502 | LP defective activation | 3MC2 |
Ficolin 3 | FCN3 | AR | 604973 | LP defective activation | Respiratory infections; abscesses |
Alternative pathway | |||||
Factor B | CFB | AD GOF | 138470 | AH50 = normal | aHUS; AMD |
AR | AH50 = 0 | Infections with encapsulated bacteria | |||
Factor D | CFD | AR | 134350 | AH50 = 0 | Neisserial infections |
Properdin | CFP | XLR | 300383 | AH50 = 0; need to employ assay that would require properdin | Neisserial infections |
Membrane attack complex | |||||
C5 | C5 | AR | 120900 | CH50 and AH50 = 0; defective bactericidal activity | Neisserial infections |
C6 | C6 | AR | 217050 | CH50 and AH50 = 0; defective bactericidal activity | |
C7 | C7 | AR | 217070 | ||
C8-alpha | C8A | AR | 120950 | ||
C8-beta | C8B | AR | 120960 | ||
C8-gamma | C8G | AR | 120930 | ||
C9 | C9 | AR | 120940 | Reduced CH50 and AH50; deficient bactericidal activity | Mild susceptibility to Neisserial infections |
Regulators and receptors | |||||
C1 inhibitor | SERPING1 | AD | 606860 | Spontaneous activation of complement; consumption of C4/C2; spontaneous activation contact system; generation of bradykinin from high molecular weight kininogen | Hereditary angioedema |
Factor I | CFI | AD | 217030 | AP activation; C3 consumption | AMD; aHUS; preeclampsia |
AR | Neisserial infections | ||||
Factor H | CFH | AD | 134370 | AP activation; C3 consumption | AMD; aHUS; preeclampsia |
AR | Neisserial infections | ||||
CD46 (membrane cofactor protein) | MCP | AD LOF | 120920 | Excessive AP activation; half normal (approximately 75% of cases) to normal levels on PBC via flow cytometry; decreased C3b/C4b binding | aHUS; HELLP syndrome; C3G |
AR | Excessive AP activation; CD46 levels absent | CVID | |||
CD55 | CD55 | AR | 125240 | Hyperactivation of complement on endothelium | CHAPLE disease = protein-losing enteropathy; thrombosis |
CD59 | CD59 | AR | 107271 | Erythrocytes highly susceptible to complement-mediated lysis | PNH-like, hemolytic anemia; polyneuropathy |
Factor H-related protein deficiencies | CFHR1 | AR or AD | 134371 | Normal CH50 and AH50; autoantibodies to factor H; linked deletions of one or more CFHR genes leads to susceptibility to autoantibody-mediated aHUS | Older onset aHUS; Neisserial infections |
CFHR2 | 600889 | ||||
CFHR3 | 605336 | ||||
CFHR4 | 605337 | ||||
CFHR5 | 608593 | ||||
Receptors | |||||
CR2 | CR2 | AR | 120650 | CVID | |
CR3 (CD11b/CD18) | ITGAM + ITGB2 | AR | 120980 | Low levels of CD11/CD18 (LFA-1 or leukocyte function antigen-1) glycoprotein | LAD I |
CR4 (CD11c/CD18) | ITGAX + ITGB2 | AR | 116920 |
AR: autosomal recessive; CP: classical pathway; AD: autosomal dominant; GOF: gain of function; LOF: loss of function; XLR: X-linked recessive; SLE: systemic lupus erythematosus; aHUS: atypical hemolytic uremic syndrome; LP: lectin pathway; AMD: age-related macular degeneration; MBL: mannose-binding lectin; MASP: mannan-binding lectin-associated protease; 3MC1: name pooled from identical but four separately named disorders; AP: alternative pathway; MAC: membrane attack complex; PBC: peripheral blood cells; HELLP: hemolysis, elevated liver enzymes, and low platelets; C3G: C3 glomerulopathy; CVID: common variable immunodeficiency; CHAPLE disease: CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and severe protein-losing enteropathy; CR2: complement receptor 2; CR3: complement receptor type 3; CR4: complement receptor type 4; LAD: leukocyte adhesion deficiency 1.
* C3 is the central component of all three activation pathways.
¶ MASP-3 is alternatively spliced from the MASP-1 gene.Do you want to add Medilib to your home screen?