Alt. symbols:

Approved name: complement C6
Alt. names: complement component 6

Location: 5p13.1: 41142116 - 41261438 (-)
Gene type: protein_coding, 11 transcripts.

Scores: LoFtool: 0.273000 | pLI: 0.00000000 | LOEUF: 0.993

HGNC: 1339

NCBI: 729, RefSeq: NG_011582.1

Ensembl: ENSG00000039537.16

LRG_29 | Status: public

OMIM: 217050

Expression | ProteinAtlas

The C6 gene encodes a serum glycoprotein (C6) that forms a membrane attack complex (MAC) together with complement components C5b, C7, C8, and C9 as part of the terminal complement pathway of the innate immune system. The MAC perforates cell membranes, forming transmembrane channels in order to facilitate cell lysis.

Biallelic mutations in C6 may cause complement C6 deficiency (C6D) [MIM:612446] or combined C6/C7 deficiency, a rare disease associated with susceptibility to severe recurrent infections, predominantly by Neisseria species. Of note, homozygous C6D has been rarely observed in Caucasians but has been reported at higher prevalence among African-Americans living in the Southeastern United States (PMID: 10632667). There have been at least 3 reports of patients with C6D presenting with SLE-like phenot ypes. Though there has been a long-standing link between monogenic lupus and early classical complement components, this has been reported since the 1980s for terminal complement components as well. Zeitz et al. (1981) noted systemic lupus erythematosus (SLE) or an SLE-like syndrome in 7% of individuals with hereditary C5, C7, C8, or C9 deficiency (PMID: 7470173). Tedesco et al. (1981) reported complete C6D in association with an SLE-like illness (PMID: 7317125) and Trapp et al. (1987) described discoid lupus, Sjogren’s and hyperthyroidism in another complete C6D patient (PMID: 3430506). Wisniewski et al. (1985) reported a third complete C6D patient presenting with a systemic rheumatic illness characterized by fever, anemia, lymphadenopathy, hepatosplenomegaly, episcleritis, and asymmetric arthritis who was found to have developed anti-C6 antibodies (PMID: 3931570). Dragon-Durey et al. (2003) identified complete C6D in 7 unrelated individuals of North or Central Africa descent living in France, of whom 4 presented with Neisseria meningitidis infections, 1 with focal and segmental glomerulosclerosis with hyalinosis, 1 with SLE and 1 with Still's disease (PMID: 12653841). Kallel-Sellami et al. (2007) reported combined homozygous C2 and C6 deficiency in a discoid lupus patient (PMID: 17893986). Most recently, in their large cohort of patients with various complement deficiencies, El-Sissy et al. (2019) found that 10 of 50 patients with C6D had some form of autoimmune disease (PMID: 31440263). [Load More]