The reference OMIM entry for this protein is 120900

Complement component 5; c5

CLONING

C5 is a 190-kD glycoprotein comprised of 2 disulfide-linked polypeptide chains, alpha (C5a) and beta (C5b), with a molecular mass of 155 and 75 kD, respectively (Tack et al., 1979). Haviland et al. (1991) constructed the complete cDNA sequence of human complement pro-C5, which is predicted to encode a 1,676-amino acid promolecule that contains an 18-amino acid leader peptide and a 4-amino acid linker separating the beta and alpha chains. Northern blot analysis demonstrated a major 6.0-kb C5 transcript, as well as 3.0-kb and 4.8-kb transcripts.

GENE FUNCTION

Karp et al. (2000) found that blockade of C5R1 (113995) in human monocytes caused marked, dose-dependent inhibition of IL12 production, as well as inhibition of TNFA (191160) secretion and IFNG (147570)-mediated suppression of IL10 (124092) production, although there was no overall effect on IL10 production. These results suggested that deficiency of C5 leads to an antiinflammatory phenotype. Karp et al. (2000) noted that previous genomewide screens had found evidence of linkage of asthma susceptibility to the C5 (Ober et al., 1998; Wjst et al., 1999) and C5R1 (Collaborative Study on the Genetics of Asthma, 1997; Ober et al., 1998) chromosomal regions.

GENE STRUCTURE

Carney et al. (1991) determined that the C5 gene contains 41 exons that span a genomic region of 79 kb.

MAPPING

By study of somatic cell hybrids using a cDNA probe and by in situ hybridization using the same probe, Jeremiah et al. (1987, 1988) assigned the C5 gene to chromosome 9q22-q34. Wetsel et al. (1988) employed in situ hybridization methods to localize the gene to band 9q32-q34. In their studies, the largest cluster of grains was found at 9q34.1.

MOLECULAR GENETICS

Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). - C5 Deficiency In affected members 2 African American families segregating C5 deficiency (609536), Wang et al. (1995) identified mutations in the C5 gene (120900.0001-120900.0002). - Poor Response To Eculizumab In 11 patients of Japanese origin with paroxysmal nocturnal hemoglobinuria (PNH; 300818) who had a poor response to treatment with the C5 inhibitor eculizumab (615749), Nishimura et al. (2014) identified a heterozygous variant in the C5 gene (R885H; 120900.0006). Both the R885H variant and wildtype C5 caused classic complement pathway hemolysis in vitro, but only wildtype C5 bound to and was blocked by eculizumab. In vitro hemolysis due to nonmutant and mutant C5 was completely blocked with the use of N19-8, a monoclonal antibody that binds to a different site on C5 than does eculizumab. A variant affecting the same residue (R885C; 120900.0007) was found in another PNH patient of Asian descent who had a poor response to eculizumab. The findings indicated that changes at this residue disrupt the eculizumab epitope on C5. - Possible Association With Rheumatoid Arthritis Plenge et al. (2007) genotyped 317,503 SNPs in a combined case-control study of 1,522 case subjects with rheumatoid arthritis (180300) and 1,850 matched control subjects. All patients were seropositive for autoantibodies against cyclic citrullinated peptide (CCP). Samples were from 2 datasets: the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Results from NARAC and EIRA for 297,086 SNPs that passed quality control filters were combined, and SNPs ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 120900 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).