Complement component 4

Complement component 4 (C4), in humans, is a protein involved in the intricate complement system, originating from the human leukocyte antigen (HLA) system, which when paired with complement component 2 (C2) is imperative in generating an immune response. C4 serves a number of critical functions in immunity, tolerance, and autoimmunity with the other numerous components.

Furthermore, it is a crucial factor in connecting the recognition pathways of the overall system instigated by antibody-antigen (Ab-Ag) complexes to the other effector proteins of the innate immune response. For example, the severity of a dysfunctional complement system can lead to fatal diseases and infections and even emotional and mental disorders like schizophrenia.

The C4 protein was initially thought to be derived from a simple two-locus allelic model, but in more recent years, popular scientific consensus has grown around a more sophisticated multi-modular RCCX gene complex model. This RCCX multi-modular model, contains long and short forms of the C4A or C4B genes which are usually in tandem with RCCX cassettes; or a mobile genetic element often containing a specific gene or set of genes along with a recombination site with copy number variation. This RCCX cassette, somewhat parallels variation in the levels of their respective proteins within a population along with CYP21 in some cases depending on the number of cassettes and whether it contains the functional gene instead of pseudogenes or fragments. Originally defined in the context of the Chido/Rodgers blood group system, the C4A-C4B genetic model is under investigation for its possible role in schizophrenia risk and development.