C4B_2: Complement C4B (Chido/Rodgers Blood Group) Gene
A key component of the complement system involved in immune defense and associated with autoimmune and infectious disease susceptibility.
Gene Information Card
| Symbol | C4B_2 |
|---|---|
| Full Name | Complement C4B (Chido/Rodgers blood group) |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.33 (within the MHC class III region) |
| NCBI Gene ID | 721 ncbi.nlm.nih.gov/gene/721 |
| Ensembl ID | ENSG00000224389 |
| UniProt ID | P0C0L5 |
| OMIM ID | 120810 |
| HGNC ID | 1324 |
| Aliases | C4B, C4B1, C4B2, C4B3, C4B5, CH, RG |
Description
C4B_2 encodes complement component 4B, a key protein of the classical and lectin complement pathways. It is part of the central complement component C4, which is cleaved into C4a and C4b. 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 and exhibits copy number variation. C4B_2 specifically refers to the C4B isotype (Chido/Rodgers blood group), which differs from C4A by a few amino acids and has distinct binding preferences.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus (SLE) | Low C4 copy number (including C4B deficiency) impairs immune complex clearance, increasing autoantibody deposition and inflammation. | OMIM #120810; multiple GWAS studies |
| Age-related macular degeneration (AMD) | Altered complement activation via C4B variants contributes to chronic inflammation in the retina. | ClinVar; PMID: 20385826 |
| Meningococcal infection | C4B deficiency reduces complement-mediated opsonization and lysis of Neisseria meningitidis. | OMIM #120810; PMID: 10931758 |
| Hereditary angioedema (HAE) | C4B deficiency (low C4 levels) is a diagnostic marker for HAE due to C1 inhibitor deficiency. | OMIM #106100; clinical guidelines |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Plasma | 8.3 | Medium |
| Spleen | 6.1 | Medium |
| Lung | 4.2 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | 15.2 | High expression; major site of C4 synthesis |
| THP-1 (monocyte) | 7.8 | Medium; monocytes produce complement components |
| A549 (lung carcinoma) | 4.1 | Low |
| HeLa (cervical carcinoma) | 2.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1216C>T (p.Arg406Cys) | missense | <0.1% | Reduced C4B hemolytic activity; associated with SLE |
| c.3622G>A (p.Gly1208Arg) | missense | <0.05% | Altered binding to C4b-binding protein; functional impact unclear |
| Complete C4B deficiency (copy number 0) | copy number variation | 1-2% in general population | Loss of C4B function; increased risk of SLE and infection |
Mutation functional classification
Loss of Function (LOF)
Complete C4B deficiency (copy number 0) leads to loss of C4B protein, impairing complement activation and immune complex clearance.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for C4B_2.
Dominant Negative (DN)
Not described for C4B_2; C4B is typically co-dominant with C4A.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement cascade (classical pathway)
• Complement cascade (lectin pathway)
• Immune system (Reactome: R-HSA-168249)
• Innate immune system (Reactome: R-HSA-168249)
Protein Summary
Complement C4B 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. C4b contains a reactive thioester bond that covalently attaches to hydroxyl groups on target surfaces (e.g., microbial cells, immune complexes). This covalent attachment is essential for opsonization and assembly of the C3 convertase (C4b2a). C4B differs from C4A by having a more efficient binding to hydroxyl-rich surfaces (e.g., carbohydrates), whereas C4A prefers amino groups. The UniProt ID for C4B_2 is P0C0L5.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C4B_2 Knockout HEK293 Cell Line | EDJ-KQ12617 | Human | 100293534 | Details Get a Quote |
| C4B_2 Knockout A-549 Cell Line | EDJ-KQ41670 | Human | 100293534 | Details Get a Quote |
| C4B_2 Knockout HCT 116 Cell Line | EDJ-KQ41671 | Human | 100293534 | Details Get a Quote |
| C4B_2 Knockout HeLa Cell Line | EDJ-KQ41672 | Human | 100293534 | Details Get a Quote |
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