C1QA Gene

C1QA (Complement C1q A Chain) is a protein coding gene located on chromosome 1p36.12. Alternative splicing results in multiple transcript variants.

The C1QA gene encodes the A-chain polypeptide of the serum complement subcomponent C1q. The protein, together with C1r and C1s, forms the first component of the serum complement system. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. C1q consists of 18 polypeptide chains, including 6 A chains, 6 B chains, and 6 C chains. Each chain contains an N-terminal collagen-like region and a C-terminal globular C1q domain.

Diseases associated with C1QA include autosomal recessive inherited C1q deficiency (OMIM: 613652) caused by a homozygous mutation in the C1QA gene due to complement deficiency of the classical component pathway.

Associated pathways include the lectin-induced complement pathway. An important paralog of this gene is C1QB.

C1q complexes with the proenzymes C1r and C1s, to form complement component C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 occurs through interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibodies in immune complexes (see Fig.)

1. Bruiners N et al. (2020) A regulatory variant in the C1Q gene cluster is associated with tuberculosis susceptibility and C1qA plasma levels in a South African population. Immunogenetics 72:305-314.
2. Hannema AJ et al (1984) SLE like syndrome and functional deficiency of C1q in members of a large family. Clin Exp Immun 55: 106-114.
3. Higuchi Yet al. (2013) The identification of a novel splicing mutation in C1qB in a Japanese family with C1q deficiency: a case report. Pediat Rheum Online J 11: 41.
4. Ling GS et al (2018) C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism. Science 360: 558-563.
5. Lopez-Lera A et al. (2014) M. Rothmund-Thomson syndrome and glomerulonephritis in a homozygous C1q-deficient patient due to a gly164ser C1qC mutation. (Letter) J Invest Derm 134: 1152-1154.