C3 Gene

The C3 gene (C3 stands for "complement C3") is a protein-coding gene located on chromosome 19p13.3.

Complement component C3 plays a central role in the activation of the complement system. Its activation is required for both the classical and alternative complement activation pathways. The encoded preprotein is proteolytically processed. This produces the alpha and beta subunits that form the mature protein.

The C3a peptide, also known as C3a anaphylatoxin, is a mediator of local inflammatory processes. It possesses antimicrobial activity. In chronic inflammation, it acts as a chemoattractant for neutrophil grnaulocytes. C3a induces smooth muscle contraction, increases vascular permeability, and causes the release of histamine from mast cells and basophilic leukocytes. C3a is a ligand for C5AR2.

C3b, once activated, can covalently bind to cell surface carbohydrates or immune aggregates via reactive thioester binding.

Mutations in the C3 gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients.

Mutations in the C3 gene induce autosomal recessive inherited C3 deficiency, and atypical hemolytic uremic syndrome. Furthermore, age-related macular degeneration is associated with C3 deficiency. Activated signaling pathways include immune response, lectin-induced complement pathway, and peptide ligand-binding receptors.

1. Berger M et al (1983) Circulating immune complexes and glomerulonephritis in a patient with congenital absence of the third component of complement. New Engl J Med 308: 1009-1012.
2. Botto M et al (1990) Molecular basis of polymorphisms of human complement component C3. J Exp Med 172: 1011-1017.
3. Cole FS et al (1985) The molecular basis for genetic deficiency of the second component of human complement. New Eng J Med 313: 11-16.
4. McLean et al (1980) Partial lipodystrophy and familial C3 deficiency. Hum. Hered. 30: 149-154.
5. McLean RH et al (1980) Familial partial deficiency of the third component of complement (C3) and the hypocomplementemic cutaneous vasculitis syndrome. Am J Med 68: 549-558.
6. Nilsson UR et al (1992) Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis. Arthritis Rheum 35: 580-586.