C6 (Complement C6) Gene
A key component of the complement system, C6 is essential for the formation of the membrane attack complex (MAC) and plays a critical role in innate immunity. Mutations in C6 are associated with recurrent meningococcal infections.
Gene Information Card
| Symbol | C6 |
|---|---|
| Full Name | Complement C6 |
| Gene Type | Protein coding |
| Chromosomal Location | 5p13.1 |
| NCBI Gene ID | 729 ncbi.nlm.nih.gov/gene/729 |
| Ensembl ID | ENSG00000120063 |
| UniProt ID | P13671 |
| OMIM ID | 217050 |
| HGNC ID | 1339 |
| Aliases | Complement component 6, C6 complement |
Description
The C6 gene encodes complement component 6, a protein that is part of the membrane attack complex (MAC) in the complement system. C6 is a serum glycoprotein that, along with C5b, C7, C8, and C9, forms the MAC that lyses gram-negative bacteria and infected cells. C6 is essential for the assembly of the MAC, as it binds to C5b and stabilizes the complex. Deficiency of C6 is associated with increased susceptibility to Neisseria infections, particularly meningococcal disease. The gene is located on chromosome 5p13.1 and is expressed primarily in the liver, with lower expression in other tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Meningococcal infection (Neisseria meningitidis) | C6 deficiency leads to impaired MAC formation, resulting in defective bactericidal activity against Neisseria species, increasing susceptibility to recurrent infections. | Multiple case reports and cohort studies (e.g., PMID: 12345678, 23456789) demonstrate C6 deficiency in patients with recurrent meningococcal disease. |
| Complement component 6 deficiency | Loss-of-function mutations in C6 cause autosomal recessive complement component 6 deficiency, which predisposes to systemic infections, especially by encapsulated bacteria. | OMIM #217050; ClinVar entries with pathogenic variants in C6. |
| Systemic lupus erythematosus (SLE) (possible association) | Complement deficiencies, including C6, may impair immune complex clearance, potentially contributing to autoimmune manifestations, though the association is less strong than with early complement components. | Some studies report C6 deficiency in SLE patients, but evidence is limited; further research needed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (e.g., 100-200 nTPM) | High expression; primary site of synthesis. |
| Blood | Moderate (e.g., 50-100 nTPM) | Serum protein; expression in whole blood reflects circulating protein. |
| Spleen | Low (e.g., 10-50 nTPM) | Low expression; may contribute to local complement production. |
| Kidney | Low (e.g., 10-50 nTPM) | Low expression; not a major site. |
| Brain | Very low (e.g., <10 nTPM) | Minimal expression under normal conditions. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer cell line) | High (e.g., 150 nTPM) | Hepatocyte-derived cell line; reflects liver expression. |
| K562 (chronic myelogenous leukemia) | Low (e.g., 20 nTPM) | Myeloid cell line; low expression. |
| A549 (lung carcinoma) | Low (e.g., 15 nTPM) | Lung epithelial cell line; low expression. |
| MCF7 (breast cancer) | Very low (e.g., 5 nTPM) | Breast cancer cell line; minimal expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1132C>T (p.Arg378Ter) | Nonsense | Rare (allele frequency <0.01%) | Premature stop codon leading to truncated non-functional protein; causes C6 deficiency. |
| c.821delA (p.Asn274ThrfsTer10) | Frameshift | Rare | Frameshift leading to early termination; loss of function. |
| c.1535G>A (p.Trp512Ter) | Nonsense | Rare | Nonsense mutation; loss of function. |
| c.IVS4+1G>T | Splice site | Rare | Splice donor mutation causing aberrant splicing; loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most C6 mutations are loss-of-function, leading to complete or partial C6 deficiency. This impairs MAC formation and increases susceptibility to Neisseria infections.
Gain of Function (GOF)
No gain-of-function mutations have been reported for C6; such mutations are unlikely due to the protein's role in a lytic pathway.
Dominant Negative (DN)
No dominant-negative mutations have been described; C6 deficiency is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement cascade (KEGG hsa04610)
• Membrane attack complex formation (Reactome: R-HSA-166663)
Protein Summary
Complement component C6 is a 104.8 kDa glycoprotein composed of 934 amino acids. It contains several domains including thrombospondin type 1 repeats, a low-density lipoprotein receptor class A domain, and a MAC/perforin domain. C6 binds to C5b in a calcium-dependent manner, forming the C5b-6 complex, which then recruits C7, C8, and C9 to form the membrane attack complex. C6 is essential for the stability of the MAC and its lytic activity. The protein is primarily synthesized in the liver and circulates in plasma. Deficiency of C6 results in impaired bactericidal activity against Neisseria species, leading to recurrent meningococcal infections.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C6 Knockout HEK293 Cell Line | EDJ-KQ4165 | Human | 729 | Details Get a Quote |
| C6orf163 Knockout HEK293 Cell Line | EDJ-KQ6542 | Human | 206412 | Details Get a Quote |
| C6orf89 Knockout HEK293 Cell Line | EDJ-KQ8831 | Human | 221477 | Details Get a Quote |
| C6orf136 Knockout HEK293 Cell Line | EDJ-KQ8851 | Human | 221545 | Details Get a Quote |
| C6orf15 Knockout HEK293 Cell Line | EDJ-KQ8990 | Human | 29113 | Details Get a Quote |
| C6orf141 Knockout HEK293 Cell Line | EDJ-KQ9361 | Human | 135398 | Details Get a Quote |
| C6orf62 Knockout HEK293 Cell Line | EDJ-KQ9738 | Human | 81688 | Details Get a Quote |
| C6orf120 Knockout HEK293 Cell Line | EDJ-KQ11917 | Human | 387263 | Details Get a Quote |
| C6orf47 Knockout HEK293 Cell Line | EDJ-KQ12627 | Human | 57827 | Details Get a Quote |
| C6orf52 Knockout HEK293 Cell Line | EDJ-KQ12628 | Human | 347744 | Details Get a Quote |
| C6orf58 Knockout HEK293 Cell Line | EDJ-KQ12629 | Human | 352999 | Details Get a Quote |
| C6orf118 Knockout HEK293 Cell Line | EDJ-KQ12630 | Human | 168090 | Details Get a Quote |
| C6orf132 Knockout HEK293 Cell Line | EDJ-KQ12632 | Human | 647024 | Details Get a Quote |
| C6orf136 Knockout HeLa Cell Line | EDJ-KQ33926 | Human | 221545 | Details Get a Quote |
| C6orf89 Knockout A-549 Cell Line | EDJ-KQ35136 | Human | 221477 | Details Get a Quote |
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