CD46: Complement Regulatory Protein and Pathogen Receptor
A multifunctional transmembrane glycoprotein involved in complement regulation, immune modulation, and susceptibility to infection and autoimmune disease.
Gene Information Card
| Symbol | CD46 |
|---|---|
| Full Name | CD46 molecule, complement regulatory protein |
| Gene Type | protein-coding |
| Chromosomal Location | 1q32.2 |
| NCBI Gene ID | 4179 ncbi.nlm.nih.gov/gene/4179 |
| Ensembl ID | ENSG00000117335 |
| UniProt ID | P15529 |
| OMIM ID | 120920 |
| HGNC ID | 6953 |
| Aliases | MCP, MIC10, TRA2.10, TLX, AHUS2 |
Description
CD46 (Membrane Cofactor Protein, MCP) is a ubiquitously expressed transmembrane glycoprotein that serves as a critical regulator of the complement system. It acts as a cofactor for factor I-mediated cleavage of C3b and C4b, thereby protecting host cells from complement-mediated damage. CD46 also functions as a receptor for several pathogens, including measles virus, human herpesvirus 6, and certain strains of Streptococcus pyogenes and Neisseria. Genetic variants in CD46 are associated with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy, and other complement-mediated disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atypical hemolytic uremic syndrome (aHUS) | Loss-of-function variants impair complement regulation on endothelial cells, leading to uncontrolled complement activation and microvascular thrombosis. | ClinVar, OMIM |
| C3 glomerulopathy (C3G) | Defective cofactor activity results in excessive C3 deposition in glomeruli. | ClinVar, OMIM |
| Hemolytic uremic syndrome, atypical, susceptibility to (AHUS2) | Heterozygous or homozygous mutations in CD46 cause familial aHUS with incomplete penetrance. | OMIM |
| Measles virus infection | CD46 serves as a cellular receptor for vaccine and laboratory-adapted measles virus strains. | UniProt, NCBI |
| Recurrent infections (Streptococcus, Neisseria) | CD46 acts as a receptor for pathogenic bacteria; altered expression may increase susceptibility. | UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 22.5 | Medium |
| Lung | 18.3 | Medium |
| Liver | 15.7 | Medium |
| Heart | 14.1 | Medium |
| Brain | 9.8 | Low |
| Spleen | 20.1 | Medium |
| Testis | 12.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 35.2 | High expression |
| HeLa | 28.6 | High expression |
| HepG2 | 22.1 | Medium expression |
| K562 | 15.3 | Medium expression |
| A549 | 19.7 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.286+2T>G | Splice donor | Rare | Loss of function; associated with aHUS |
| p.Ser206Pro | Missense | Rare | Impaired cofactor activity; aHUS |
| p.Arg103Trp | Missense | Rare | Reduced cell surface expression; aHUS |
| p.Gly61Arg | Missense | Rare | Defective C3b binding; aHUS |
| c.565-1G>A | Splice acceptor | Rare | Skipping of exon 6; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most CD46 mutations in aHUS are loss-of-function, leading to reduced cofactor activity or decreased cell surface expression, resulting in impaired complement regulation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in CD46.
Dominant Negative (DN)
Some heterozygous mutations may exert a dominant-negative effect by interfering with wild-type CD46 function, though haploinsufficiency is more common.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 – protein binding | • GO:0005886 – plasma membrane |
| • GO:0007338 – single fertilization | • GO:0009986 – cell surface |
| • GO:0016021 – integral component of membrane | • GO:0030449 – regulation of complement activation |
| • GO:0045087 – innate immune response | • GO:0050829 – defense response to Gram-negative bacterium |
| • GO:0050830 – defense response to Gram-positive bacterium | • GO:1903561 – extracellular vesicle |
Pathways
• Complement cascade (Reactome: R-HSA-166658)
• Regulation of complement cascade (Reactome: R-HSA-977606)
• Measles virus infection (KEGG: hsa05162)
• Staphylococcus aureus infection (KEGG: hsa05150)
Protein Summary
CD46 is a type I transmembrane glycoprotein composed of four short consensus repeats (SCRs) in the extracellular domain, a serine/threonine-rich region, a transmembrane domain, and a cytoplasmic tail. It binds C3b and C4b and serves as a cofactor for factor I-mediated proteolytic inactivation, protecting host cells from complement attack. CD46 is expressed on all nucleated cells and is involved in T-cell regulation, fertilization, and pathogen recognition. Alternative splicing generates multiple isoforms differing in the cytoplasmic domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD46 Knockout HEK293 Cell Line | EDC09605 | Human | 4179 | Details Get a Quote |
| CD46 Knockout A-549 Cell Line | EDJ-KQ19828 | Human | 4179 | Details Get a Quote |
| CD46 Knockout HCT 116 Cell Line | EDJ-KQ19829 | Human | 4179 | Details Get a Quote |
| CD46 Knockout HeLa Cell Line | EDJ-KQ19830 | Human | 4179 | Details Get a Quote |
| CD46 and CD55 and CD59 Knockout HEK293 Cell Line | EDC08362 | Human | 4179 and 1604 and 966 | Details Get a Quote |
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