C4A: Complement C4A (Chido/Rodgers Blood Group)
A key component of the classical complement pathway involved in immune defense and associated with autoimmune and infectious disease susceptibility.
Gene Information Card
| Symbol | C4A |
|---|---|
| Full Name | Complement C4A (Chido/Rodgers blood group) |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.33 (MHC class III region) |
| NCBI Gene ID | 720 ncbi.nlm.nih.gov/gene/720 |
| Ensembl ID | ENSG00000244731 |
| UniProt ID | P0C0L4 |
| OMIM ID | 120810 |
| HGNC ID | 1323 |
| Aliases | C4A2, C4A3, C4A4, C4A6, C4S, CO4, CPAMD2, RG |
Description
The C4A gene encodes complement component 4A, a key protein of the classical and lectin complement activation pathways. C4A is part of the central complement component C4, which is cleaved into C4a and C4b fragments. C4b covalently binds to pathogen surfaces and immune complexes, facilitating opsonization and activation of the downstream complement cascade. The gene is located in the MHC class III region on chromosome 6 and exhibits copy number variation (CNV) that influences susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and infections. C4A also carries the Rodgers (Rg) blood group antigens.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus (SLE) | Low copy number or deficiency of C4A reduces clearance of immune complexes, leading to tissue deposition and inflammation. | OMIM #120810; PMID: 12033749 |
| Complement C4A deficiency | Homozygous or heterozygous deficiency impairs classical pathway activation, increasing risk for immune complex diseases and infections. | OMIM #120810; ClinVar |
| Infectious diseases (e.g., meningococcal infection) | Deficient C4A compromises opsonization and lysis of encapsulated bacteria. | PMID: 10799849 |
| Age-related macular degeneration (AMD) | Altered complement regulation involving C4A variants may contribute to chronic inflammation in the retina. | PMID: 20385826 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 78.5 | High |
| Adrenal gland | 12.3 | Medium |
| Kidney | 8.9 | Medium |
| Lung | 6.2 | Low |
| Spleen | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 85.2 | Hepatocyte line, high expression |
| THP-1 (monocyte) | 22.4 | Macrophage-like, moderate expression |
| A549 (lung) | 4.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.331C>T (p.Arg111*) | Nonsense | Rare | Loss of function; associated with C4A deficiency |
| c.925G>A (p.Gly309Arg) | Missense | 0.1% in European populations | May affect C4A function; reported in ClinVar |
| Copy number variation (CNV) | Structural variant | Variable (0-4 copies) | Low copy number increases SLE risk |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or absent C4A protein; copy number loss reduces protein levels.
Gain of Function (GOF)
Not described for C4A; gain-of-function is not a recognized mechanism for this gene.
Dominant Negative (DN)
Not reported; C4A deficiency is typically recessive or due to CNV.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement cascade (classical pathway) – Reactome R-HSA-166663
• Complement and coagulation cascades – KEGG hsa04610
• Immune system – Reactome R-HSA-168256
Protein Summary
Complement C4A is a 1744-amino-acid glycoprotein synthesized primarily in the liver and secreted into plasma. It is cleaved by C1s into C4a (anaphylatoxin) and C4b, which covalently attaches to target surfaces via its thioester bond. C4b then binds C2 to form the C3 convertase (C4b2a), propagating the complement cascade. C4A preferentially binds to immune complexes and protein antigens, while its isotype C4B binds to carbohydrate-rich surfaces. The protein carries the Rodgers blood group antigens. Deficiency or low copy number of C4A is a strong genetic risk factor for SLE.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C4A Knockout HEK293 Cell Line | EDJ-KQ50165 | Human | 720 | Details Get a Quote |
| C4A Knockout HeLa Cell Line | EDJ-KQ52745 | Human | 720 | Details Get a Quote |
| C4A Knockout A-549 Cell Line | EDJ-KQ61217 | Human | 720 | Details Get a Quote |
| C4A Knockout HCT 116 Cell Line | EDJ-KQ69710 | Human | 720 | Details Get a Quote |
