Alt. symbols: MIC10 | MCP | TRA2.10 | MGC26544 | TLX

Approved name: CD46 molecule
Alt. names: antigen identified by monoclonal antibody TRA-2-10, membrane cofactor protein (CD46, trophoblast-lymphocyte cross-reactive antigen), CD46 antigen, complement regulatory protein, CD46 molecule, complement regulatory protein

Location: 1q32.2: 207752037 - 207795513 (+)
Gene type: protein_coding, 33 transcripts.

Scores: LoFtool: 0.983000 | pLI: 0.00019160 | LOEUF: 0.896

HGNC: 6953

NCBI: 4179, RefSeq: NG_009296.1

Ensembl: ENSG00000117335.21

LRG_155 | Status: public

OMIM: 120920

Expression | ProteinAtlas

The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded protein has cofactor activity for inactivation of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. In addition, the encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6, and type IV pili of pathogenic Neisseria. Finally, the protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization.

Noris et al. (2003) were the first to report the association of a heterozygous mutation in this gene (MCP/CD46) with atypical hemolytic uremic syndrome in 2 patients. The mutation caused a premature stop codon, which resulted in loss of the transmembrane domain of the protein and severely reduced cell-surface expression of MCP. Like factor H (CFH), MCP inhibits complement activation by regulating C3b deposition on targets. Richards et al. (2003) hypothesized that MCP mutations could predispose t o aHUS and identified mutations in the MCP gene in affected members from 3 of 30 affected families: a heterozygous 6-bp deletion in one family and a p.S206P mutation, which was heterozygous in one family and homozygous in another. An individual with the 6-bp deletion had reduced MCP levels and approximately 50% C3b binding compared with normal controls. Individuals with the S206P mutation expressed normal quantities of protein, but demonstrated approximately 50% reduction in C3b binding in heterozygotes and complete lack of C3b binding in homozygotes. Studies in transfectants showed that the deletion mutant was retained intracellularly. S206P protein was expressed on the cell surface but had a reduced ability to prevent complement activation, consistent with its reduced C3b binding and cofactor activity. Esparza-Gordillo et al. (2005) identified a specific SNP haplotype in the MCP gene, which was overrepresented in aHUS patients and strongly associated with the severity of the disease. Linkage disequilibrium analysis suggested that the haplotype included the CR1, DAF (CD55), and C4BPA genes. Two SNPs in the haplotype influenced the transcription activity of the MCP promoter in transient transfection experiments. The SNP haplotype block was particularly frequent among patients who carried mutations in HF1 (CFH), MCP, or FI (CFI). Esparza-Gordillo et al. (2005) suggested that complement regulatory molecules may act as a protein network, and that multiple mutations involving plasma- and membrane-associated complement regulatory proteins are necessary to impair protection of host tissues and to confer significant predisposition to aHUS. Fremeaux-Bacchi et al. (2005) examined single-nucleotide polymorphisms (SNPs) in both the CFH and the MCP genes in 2 large cohorts of HUS. In both cohorts there was an association with HUS for both CFH and MCP alleles. Furthermore, CFH and MCP haplotypes were significantly different in HUS patients compared with controls. The results suggested that there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical HUS. A characteristic feature of both MCP- and CFH-associated HUS is reduced penetrance and variable inheritance. Caprioli et al. (2006) identified 14 mutations in the MCP gene in 20 (12.8%) of 156 patients with atypical HUS. Three patients from 1 family were compound heterozygotes, 2 patients from 1 family carried a homozygous mutation, and the others were heterozygotes. In addition, the 3 patients from 1 family also carried a mutation in the CFH gene. Most (93%) MCP mutations clustered in the 4 SCRs at the N-terminal region of MCP, indicating the importance of this region for complement regulation. The mutations resulted in either reduced protein expression or impaired C3b binding capability. Analyses of available relatives revealed a penetrance of 54%.[source:OMIM] [Load More]