Gene SymbolCD46
Full NameCD46 Molecule (Membrane Cofactor Protein)
Chromosomal Location1q32.2
Ensembl IDENSG00000108539
Associated DiseasesAge-Related Macular Degeneration, Multiple Sclerosis
The CD46 gene encodes membrane cofactor protein (MCP), a crucial complement regulatory protein expressed on all nucleated cells. CD46 is a type I membrane protein that serves as a cofactor for factor I-mediated cleavage of C3b and C4b, protecting cells from complement-mediated damage [1].
CD46 is a member of the regulators of complement activation (RCA) gene family. The protein exists in multiple isoforms generated by alternative splicing, with different cytoplasmic tails that can signal differently. CD46 also serves as a receptor for several pathogens, including measles virus, adenovirus, and Streptococcus pyogenes [2].
The CD46 protein functions as:
- Complement Regulation: Serves as a cofactor for factor I cleavage of C3b and C4b, preventing complement activation on host cells
- Host Cell Protection: Protects cells from complement-mediated lysis by regulating C3b deposition
- Pathogen Receptor: Serves as a receptor for measles virus, adenovirus types 2 and 5, and Streptococcus pyogenes
- Immune Modulation: Modulates T cell function and promotes regulatory T cell development
- Signal Transduction: Can trigger intracellular signaling upon ligand binding
- CD46 variants are associated with AMD risk
- CD46 plays a role in retinal pigment epithelial cell protection
- Altered complement regulation contributes to drusen formation
- CD46 is implicated in MS pathogenesis
- Regulates immune cell function and neuroinflammation
- May influence disease progression and severity
- Atypical Hemolytic Uremic Syndrome: CD46 mutations can contribute to aHUS
- Chronic Lymphocytic Leukemia: CD46 overexpression may promote immune evasion
- Asthma: CD46 variants associated with disease severity
- Ubiquitous: Expressed on most nucleated cells
- Brain: Neurons, astrocytes, microglia express CD46
- Immune cells: High expression on leukocytes
- Epithelial cells: Strong expression on mucosal surfaces
- Cytokines can modulate CD46 expression
- IFN-α and IFN-β upregulate CD46
- Cell activation increases CD46 surface expression
- Located at 1q32.2 in the RCA gene cluster
- Multiple isoforms generated by alternative splicing
- Polymorphisms affect disease susceptibility
- Therapeutic Target: CD46-targeted therapies in development for cancer and infections
- Biomarker: CD46 expression levels may have diagnostic utility
- Vaccine Vector: CD46 used as receptor for viral vaccine vectors
- Riley-Vargas et al., CD46: a viral receptor and complement regulator (2005)
- Liszewski et al., Membrane cofactor protein (MCP) function (2005)
- Kemper et al., CD46 in T cell activation (2003)
- Astier et al., CD46 and adaptive immunity (2006)
- Cardone et al., CD46 signaling in T cells (2010)
- Fischer et al., CD46 and viral pathogenesis (2006)
- Wang et al., CD46 in neurodegeneration (2012)
- Crawford et al., Complement regulators in brain (2003)