C3 Gene - Complement C3: Function, Mutations, and Disease Associations

The C3 gene encodes complement component 3, a central protein of the complement system. C3 is synthesized primarily by the liver and plays a critical role in innate immunity by opsonizing pathogens, promoting inflammation, and forming the membrane attack complex. Proteolytic cleavage generates active fragments C3a (anaphylatoxin) and C3b (opsonin). Mutations in C3 are associated with atypical hemolytic uremic syndrome, age-related macular degeneration, and C3 glomerulopathy.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Complement cascade (Reactome: R-HSA-166658)

• Alternative complement activation (Reactome: R-HSA-173736)

• Classical antibody-mediated complement activation (Reactome: R-HSA-173623)

• Lectin pathway of complement activation (Reactome: R-HSA-166662)

• Immune system (KEGG: hsa04610)

Complement C3 is a 1663-amino-acid glycoprotein (185 kDa) synthesized as a single-chain precursor, then proteolytically processed into alpha and beta chains linked by disulfide bonds. It is the most abundant complement protein in serum (~1.3 mg/mL). C3 is cleaved by C3 convertase into C3a (anaphylatoxin) and C3b (opsonin). C3b covalently attaches to pathogen surfaces, marking them for phagocytosis, and initiates the formation of the membrane attack complex. C3a promotes inflammation via chemotaxis and mast cell degranulation. Regulation by factors H and I prevents excessive activation. Mutations disrupting regulation lead to renal and retinal diseases.