Table 8.

Complement deficiencies

DiseaseGenetic defectInheritanceGene OMIMLaboratory featuresAssociated features
Complement deficiencies 
C1q deficiency due to defects C1QA AR 120550 Absent CH50 hemolytic activity, defective activation of the classical pathway, diminished clearance of apoptotic cells SLE, infections with encapsulated organisms 
C1QB AR 120570 
C1QC AR 120575 
C1r deficiency C1R AR 613785 Absent CH50 hemolytic activity, defective activation of the classical pathway SLE, infections with encapsulated organisms, Ehlers–Danlos phenotype 
C1r Periodontal Ehlers–Danlos C1R AD GOF 613785 Normal CH50 Hyperpigmentation, skin fragility 
C1s deficiency C1S AR 613785 Absent CH50 hemolytic activity, defective activation of the classical pathway SLE, infections with encapsulated organisms, Ehlers–Danlos phenotype 
C1s Periodontal Ehlers–Danlos C1S AD GOF 613785 Normal CH50 Hyperpigmentation, skin fragility 
Complete C4 deficiency C4A+C4B AR 120810 Absent CH50 hemolytic activity, defective activation of the classical pathway, complete deficiency requires biallelic mutations/deletions/conversions of both C4A and C4B SLE, infections with encapsulated organisms, partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense 
C2 deficiency C2 AR 217000 Absent CH50 hemolytic activity, defective activation of the classical pathway SLE, infections with encapsulated organisms, atherosclerosis 
C3 deficiency (LOF) C3 AR 120700 Absent CH50 and AH50 hemolytic activity, defective opsonization, defective humoral immune response Infections, glomerulonephritis, atypical hemolytic–uremic syndrome with GOF mutations 
C3 GOF C3 AD GOF 120700 Increased activation of complement Atypical hemolytic–uremic syndrome 
C5 deficiency C5 AR 120900 Absent CH50 and AH50 hemolytic activity
Defective bactericidal activity 		Disseminated neisserial infections 
C6 deficiency C6 AR 217050 Absent CH50 and AH50 hemolytic activity, defective bactericidal activity 
C7 deficiency C7 AR 217070 
C8α deficiency C8A AR 120950 
C8γ deficiency C8G AR 120930 
C8β deficiency C8B AR 120960 
C9 deficiency C9 AR 120940 Reduced CH50 and AP50 hemolytic activity, deficient bactericidal activity Mild susceptibility to disseminated neisserial infections 
MASP2 deficiency MASP2 AR 605102 Deficient activation of the lectin activation pathway Pyogenic infections, inflammatory lung disease, autoimmunity 
Ficolin-3 deficiency FCN3 AR 604973 Absence of complement activation by the ficolin-3 pathway Respiratory infections, abscesses 
C1 inhibitor deficiency SERPING1 AD/AR 606860 Spontaneous activation of the complement pathway with consumption of C4/C2, spontaneous activation of the contact system with generation of bradykinin from high molecular weight kininogen Hereditary angioedema 
Factor B GOF CFB AD GOF 612924 GOF mutation with increased spontaneous AH50 Atypical hemolytic–uremic syndrome 
Factor B deficiency CFB AR 615561 Deficient activation of the alternative pathway Infections with encapsulated organisms 
Factor D deficiency CFD AR 134350 Absent AH50 hemolytic activity Neisserial infections 
Properdin deficiency CFP XL 300383 Absent AH50 hemolytic activity Neisserial infections 
Factor I deficiency CFI AR 217030 Spontaneous activation of the alternative complement pathway with consumption of C3 Infections, disseminated neisserial infections, atypical hemolytic–uremic syndrome, preeclampsia 
Factor H deficiency CFH AR or AD 134370 Spontaneous activation of the alternative complement pathway with consumption of C3 
Factor H–related protein deficiencies CFHR1 AR or AD 134371 Normal CH50, AH50, autoantibodies to factor H, linked deletions of one or more CFHR genes lead to susceptibility to autoantibody-mediated aHUS Older onset atypical hemolytic–uremic syndrome, disseminated neisserial infections 
CFHR2 600889 
CFHR3 605336 
CFHR4 605337 
CFHR5 608593 
Thrombomodulin deficiency THBD AD 188040 Normal CH50, AH50 Atypical hemolytic–uremic syndrome 
Membrane cofactor protein (CD46) deficiency CD46 AD/AR 120920 Inhibitor of complement alternate pathway, decreased C3b binding Atypical hemolytic–uremic syndrome, infections, preeclampsia 
Membrane attack complex inhibitor (CD59) deficiency CD59 AR 107271 Erythrocytes highly susceptible to complement-mediated lysis Hemolytic anemia, polyneuropathy 
CD55 deficiency (CHAPLE disease) CD55 AR 125240 Hyperactivation of complement on endothelium Protein losing enteropathy, thrombosis 
DiseaseGenetic defectInheritanceGene OMIMLaboratory featuresAssociated features
Complement deficiencies 
C1q deficiency due to defects C1QA AR 120550 Absent CH50 hemolytic activity, defective activation of the classical pathway, diminished clearance of apoptotic cells SLE, infections with encapsulated organisms 
C1QB AR 120570 
C1QC AR 120575 
C1r deficiency C1R AR 613785 Absent CH50 hemolytic activity, defective activation of the classical pathway SLE, infections with encapsulated organisms, Ehlers–Danlos phenotype 
C1r Periodontal Ehlers–Danlos C1R AD GOF 613785 Normal CH50 Hyperpigmentation, skin fragility 
C1s deficiency C1S AR 613785 Absent CH50 hemolytic activity, defective activation of the classical pathway SLE, infections with encapsulated organisms, Ehlers–Danlos phenotype 
C1s Periodontal Ehlers–Danlos C1S AD GOF 613785 Normal CH50 Hyperpigmentation, skin fragility 
Complete C4 deficiency C4A+C4B AR 120810 Absent CH50 hemolytic activity, defective activation of the classical pathway, complete deficiency requires biallelic mutations/deletions/conversions of both C4A and C4B SLE, infections with encapsulated organisms, partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense 
C2 deficiency C2 AR 217000 Absent CH50 hemolytic activity, defective activation of the classical pathway SLE, infections with encapsulated organisms, atherosclerosis 
C3 deficiency (LOF) C3 AR 120700 Absent CH50 and AH50 hemolytic activity, defective opsonization, defective humoral immune response Infections, glomerulonephritis, atypical hemolytic–uremic syndrome with GOF mutations 
C3 GOF C3 AD GOF 120700 Increased activation of complement Atypical hemolytic–uremic syndrome 
C5 deficiency C5 AR 120900 Absent CH50 and AH50 hemolytic activity
Defective bactericidal activity 		Disseminated neisserial infections 
C6 deficiency C6 AR 217050 Absent CH50 and AH50 hemolytic activity, defective bactericidal activity 
C7 deficiency C7 AR 217070 
C8α deficiency C8A AR 120950 
C8γ deficiency C8G AR 120930 
C8β deficiency C8B AR 120960 
C9 deficiency C9 AR 120940 Reduced CH50 and AP50 hemolytic activity, deficient bactericidal activity Mild susceptibility to disseminated neisserial infections 
MASP2 deficiency MASP2 AR 605102 Deficient activation of the lectin activation pathway Pyogenic infections, inflammatory lung disease, autoimmunity 
Ficolin-3 deficiency FCN3 AR 604973 Absence of complement activation by the ficolin-3 pathway Respiratory infections, abscesses 
C1 inhibitor deficiency SERPING1 AD/AR 606860 Spontaneous activation of the complement pathway with consumption of C4/C2, spontaneous activation of the contact system with generation of bradykinin from high molecular weight kininogen Hereditary angioedema 
Factor B GOF CFB AD GOF 612924 GOF mutation with increased spontaneous AH50 Atypical hemolytic–uremic syndrome 
Factor B deficiency CFB AR 615561 Deficient activation of the alternative pathway Infections with encapsulated organisms 
Factor D deficiency CFD AR 134350 Absent AH50 hemolytic activity Neisserial infections 
Properdin deficiency CFP XL 300383 Absent AH50 hemolytic activity Neisserial infections 
Factor I deficiency CFI AR 217030 Spontaneous activation of the alternative complement pathway with consumption of C3 Infections, disseminated neisserial infections, atypical hemolytic–uremic syndrome, preeclampsia 
Factor H deficiency CFH AR or AD 134370 Spontaneous activation of the alternative complement pathway with consumption of C3 
Factor H–related protein deficiencies CFHR1 AR or AD 134371 Normal CH50, AH50, autoantibodies to factor H, linked deletions of one or more CFHR genes lead to susceptibility to autoantibody-mediated aHUS Older onset atypical hemolytic–uremic syndrome, disseminated neisserial infections 
CFHR2 600889 
CFHR3 605336 
CFHR4 605337 
CFHR5 608593 
Thrombomodulin deficiency THBD AD 188040 Normal CH50, AH50 Atypical hemolytic–uremic syndrome 
Membrane cofactor protein (CD46) deficiency CD46 AD/AR 120920 Inhibitor of complement alternate pathway, decreased C3b binding Atypical hemolytic–uremic syndrome, infections, preeclampsia 
Membrane attack complex inhibitor (CD59) deficiency CD59 AR 107271 Erythrocytes highly susceptible to complement-mediated lysis Hemolytic anemia, polyneuropathy 
CD55 deficiency (CHAPLE disease) CD55 AR 125240 Hyperactivation of complement on endothelium Protein losing enteropathy, thrombosis 

MAC, membrane attack complex; SLE, systemic lupus erythematosus.

Total number of mutant genes in Table 8: 36.

New disorders: None.

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