C1QA

C1QA is a gene that encodes the A subunit of the C1q component of the complement system. C1q is the recognition subcomponent of the classical pathway of complement activation and is essential for initiating the proteolytic cascade that leads to pathogen clearance and inflammation. The active C1 complex is composed of C1q bound to a tetramer of proteases, C1r2 and C1s2. C1q itself is a hexamer formed from six heterotrimeric subunits, each containing A, B, and C chains, arranged to create a bouquet-like particle with globular heads that bind to the Fc regions of antibodies or to surface ligands on pathogens and apoptotic cells.

The C1QA gene is located on chromosome 1 and is part of a gene cluster that includes C1QB and C1QC. Expression is detected in a range of cell types, including monocytes, macrophages, dendritic cells, and microglia, with C1q circulating in the bloodstream as a serum protein. The A chain, together with the B and C chains, forms the functional C1q molecule that recognizes immune complexes and other targets to trigger complement activation.

In clinical relevance, C1q deficiency, arising from mutations in C1QA or related genes, is a major genetic risk factor for systemic lupus erythematosus (SLE). Altered C1q levels and activity are observed in various autoimmune and inflammatory conditions. In the central nervous system, microglial C1q participates in development and synaptic pruning, and has been implicated in neurodegenerative processes through its interactions with dying cells and aggregates.