Complement regulator CD46: genetic variants and disease associations

Hum Genomics. 2015 Jun 10;9(1):7. doi: 10.1186/s40246-015-0029-z.


Membrane cofactor protein (MCP; CD46) is an ubiquitously expressed complement regulatory protein that protects host cells from injury by complement. This type-I membrane glycoprotein serves as a cofactor for the serine protease factor I to mediate inactivation of C3b and C4b deposited on host cells. More than 60 disease-associated mutations in MCP have now been identified. The majority of the mutations are linked to a rare thrombotic microangiopathic-based disease, atypical hemolytic uremic syndrome (aHUS), but new putative links to systemic lupus erythematosus, glomerulonephritis, and pregnancy-related disorders among others have also been identified. This review summarizes our current knowledge of disease-associated mutations in this complement inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Complement C3b / genetics
  • Complement C3b / metabolism
  • Complement C4b / genetics
  • Complement C4b / metabolism
  • Female
  • Glomerulonephritis / genetics*
  • Glomerulonephritis / pathology
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / pathology
  • Membrane Cofactor Protein / genetics*
  • Membrane Cofactor Protein / metabolism
  • Mutation
  • Pregnancy
  • Pregnancy Complications / genetics


  • CD46 protein, human
  • Membrane Cofactor Protein
  • Complement C3b
  • Complement C4b