C8A Gene: Complement C8 Alpha Chain
Genetic and functional insights into the complement C8 alpha subunit, its role in the membrane attack complex, and associated deficiencies.
Gene Information Card
| Symbol | C8A |
|---|---|
| Full Name | Complement C8 alpha chain |
| Gene Type | protein-coding |
| Chromosomal Location | 1p32.2 |
| NCBI Gene ID | 731 ncbi.nlm.nih.gov/gene/731 |
| Ensembl ID | ENSG00000157110 |
| UniProt ID | P07357 |
| OMIM ID | 120950 |
| HGNC ID | 1326 |
| Aliases | C8, complement component 8, alpha polypeptide |
Description
The C8A gene encodes the alpha subunit of complement component 8 (C8), a constituent of the membrane attack complex (MAC) that mediates cell lysis of pathogens. C8 is a heterotrimer composed of alpha, beta, and gamma chains. The alpha chain is covalently linked to the gamma chain, and the alpha-gamma dimer is disulfide-bonded to the beta chain. C8 binds to the C5b-7 complex and facilitates the insertion of C9 to form the lytic pore. Mutations in C8A cause complement C8 deficiency, which is associated with increased susceptibility to Neisseria infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Complement component 8 deficiency | Loss-of-function mutations in C8A lead to absence or dysfunction of the C8 alpha chain, preventing MAC formation and impairing bactericidal activity against Neisseria species. | OMIM 120950; ClinVar; PMID: 23431077 |
| Meningococcal disease (recurrent) | C8 deficiency impairs the terminal complement pathway, increasing susceptibility to recurrent Neisseria meningitidis infections. | OMIM; PMID: 23431077 |
| Systemic lupus erythematosus (SLE) (association) | Complement deficiencies, including C8, may predispose to autoimmune diseases due to impaired clearance of immune complexes and apoptotic cells. | PMID: 23431077; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 31.5 | High |
| Plasma | N/A | Secreted |
| Kidney | 5.2 | Low |
| Testis | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 28.7 | Hepatocyte cell line |
| K562 (leukemia) | 0.8 | Low expression |
| HeLa (cervical) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.965C>T (p.Arg322Ter) | Nonsense | Rare | Premature stop codon leading to truncated protein and C8 deficiency |
| c.1282C>T (p.Arg428Cys) | Missense | Rare | Disrupts protein folding or interaction, causing functional deficiency |
| c.165delG (p.Leu56TrpfsTer19) | Frameshift | Rare | Frameshift leading to loss of function |
Mutation functional classification
Loss of Function (LOF)
Most C8A mutations are loss-of-function, resulting in C8 deficiency and impaired MAC formation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for C8A.
Dominant Negative (DN)
C8 deficiency is inherited in an autosomal recessive manner; no dominant-negative effects are documented.
View complete mutation data：
Gene Ontology (GO)
| • complement activation | • membrane attack complex |
| • immune response | • protein binding |
| • cell lysis | • pore formation |
Pathways
• Complement cascade
• Membrane attack complex formation
• Immune system
Protein Summary
The C8 alpha chain is a 584-amino acid glycoprotein that forms a disulfide-linked heterodimer with the C8 gamma chain. This alpha-gamma dimer associates with the C8 beta chain to form the mature C8 protein. C8 is part of the membrane attack complex, where it binds to C5b-7 and recruits C9, leading to pore formation and osmotic lysis of target cells. The alpha chain contains a MACPF domain essential for membrane insertion. Defects in C8A lead to complement C8 deficiency, characterized by recurrent Neisseria infections.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC8A1 Knockout HEK293 Cell Line | EDJ-KQ849 | Human | 6546 | Details Get a Quote |
| SLC8A2 Knockout HEK293 Cell Line | EDJ-KQ1432 | Human | 6543 | Details Get a Quote |
| SLC8A3 Knockout HEK293 Cell Line | EDJ-KQ1433 | Human | 6547 | Details Get a Quote |
| LRRC8A Knockout HEK293 Cell Line | EDJ-KQ3564 | Human | 56262 | Details Get a Quote |
| C8A Knockout HEK293 Cell Line | EDJ-KQ4168 | Human | 731 | Details Get a Quote |
| KLHDC8A Knockout HEK293 Cell Line | EDJ-KQ13950 | Human | 55220 | Details Get a Quote |
| LRRC8A Knockout HeLa Cell Line | EDJ-KQ24056 | Human | 56262 | Details Get a Quote |
| LRRC8A Knockout A-549 Cell Line | EDJ-KQ25431 | Human | 56262 | Details Get a Quote |
| LRRC8A Knockout HCT 116 Cell Line | EDJ-KQ25432 | Human | 56262 | Details Get a Quote |
| C8A Knockout HeLa Cell Line | EDJ-KQ52751 | Human | 731 | Details Get a Quote |
| SLC8A2 Knockout HeLa Cell Line | EDJ-KQ54498 | Human | 6543 | Details Get a Quote |
| SLC8A1 Knockout HeLa Cell Line | EDJ-KQ54500 | Human | 6546 | Details Get a Quote |
| SLC8A3 Knockout HeLa Cell Line | EDJ-KQ54501 | Human | 6547 | Details Get a Quote |
| KLHDC8A Knockout HeLa Cell Line | EDJ-KQ56558 | Human | 55220 | Details Get a Quote |
| C8A Knockout A-549 Cell Line | EDJ-KQ61221 | Human | 731 | Details Get a Quote |
Displaying Records 1 To 15 Of 24 Records
