Table 1.
Complement gene variants and associated diseases.
| Gene | Variant | Disease |
|---|---|---|
| C1q | Deficiency Polymorphism |
Increased risk of lupus and glomerulonephritis Arthritis, cancer, diabetes, schizophrenia |
| C1r/C1s | Deficiency GOF SNP |
Autoimmunity, infections, glomerulonephritis, Type I periodontal Ehlers-Danlos Increased risk of AD |
| C1INH | Deficiency | Hereditary angioedema (types I and II) |
| C2 | Deficiency SNPs |
Lupus, bacterial infections Protective for AMD and PCVP |
| C3 | GOF Nonsynonymous Coding variant |
aHUS, C3G, and AMD |
| C4 | Deficiency CNV |
Lupus Schizophrenia |
| C5 | Nonsense; hom or Compound het |
C5 deficiency; neisserial infections |
| C6 | Single bp deletion | C6 deficiency; neisserial infections |
| C7 | Nonsense: hom or compound het | C7 deficiency; neisserial infections |
| C8α | Nonsense: hom or compound het | C8 deficiency, type I; neisserial infections; no C8α protein; free C8β |
| C8β | Premature stop codon | C8 deficiency, type II; neisserial infections; no C8β protein; free C8α |
| C9 | Nonsense: hom or compound het SNPs |
C9 deficiency; neisserial infections AMD; AD |
| MASP-1, collectins | Hom/het deficiency | Various developmental; Malpuech, Carnevale, Michels, and Mingarelli syndrome |
| Ficolins | SNPs | Rheumatoid arthritis, leprosy, systemic inflammation, bacterial infections |
| CFH | Hom deficiency SNPs and truncations |
DDD; MPGN C3G; acquired partial lipodystrophy; aHUS AMD; AD; Some protective against meningococcal disease, AMD, IgAN, or C3G |
| CFI | Nonsense: hom, het or compound het | AMD; C3G; aHUS; recurrent infections |
| MCP | Hom/Het deletion/truncation Missense SNP |
Systemic sclerosis, miscarriage, HELLP syndrome, and C3G Severe aHUS; linked to CVID |
| CFB | Nonsense: hom or compound het Het GOF SNP Other SNPs |
Factor B deficiency; recurrent bacterial infections aHUS Protection against AMD |
| Properdin | Nonsense/truncating mutations | Properdin deficiency (X-linked); neisserial infections |
| DAF | Nonsense: hom or compound het | CHAPLE Syndrome; linked to Inab Cromer blood group |
| CD59 | Nonsense: hom or compound het | CD59 deficiency; PNH-like disease; Peripheral neuropathy; strokes |
| CFHR1/3 | Combined gene deletion | Risk for aHUS; protection from AMD |
| CFHR5 | Gene duplication SNPs |
aHUS C3G; poststreptococcal glomerulonephritis |
| Clu | SNPs | AD |
| CR1 | SNPs | AD |
AD—Alzheimer’s disease, aHUS—atypical haemolytic uremic syndrome, AMD—age-related macular degeneration, bp—basepair, C3G—complement 3 glomerulopathy, CHAPLE—complement hyperactivity, angiopathic thrombosis, and protein-losing enteropathy, CNV—copy number variant, CVID—common variable immunodeficiency, DDD—dense deposit disease, GOF—gain of function, het—heterozygous, hom—homozygous, MPGN—membranoproliferative glomerulonephritis, LOF—loss of function, PCVP—polypoidal choroidal vasculopathy, PNH—paroxysmal nocturnal hemoglobinuria, SNP—single nucleotide polymorphism.