Mutations in CD46, a complement regulatory protein, predispose to atypical HUS

Trends Mol Med. 2004 May;10(5):226-31. doi: 10.1016/j.molmed.2004.03.006.

Abstract

Membrane cofactor protein (MCP, CD46) is a widely expressed transmembrane complement regulator. As does the soluble regulator factor H, it inhibits complement activation by inactivating the C3b that is deposited on target membranes. Factor H mutations have been described in 15-30% of patients with atypical haemolytic uraemic syndrome (HUS). Recent studies have identified mutations in the MCP gene in four families. In one, a heterozygous deletion resulted in the intracellular retention of the mutant protein. In another, a different heterozygous deletion led to a premature stop codon and the loss of the C-terminus. In the other two, a substitution (S206P) resulted in cell-surface expression but inefficient inactivation of surface-bound C3b. These findings provide further evidence that complement dysregulation predisposes to the development of HUS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Membrane / immunology*
  • Codon, Nonsense
  • Complement Activation / genetics
  • Complement C3b / metabolism
  • Complement Factor H / genetics
  • Genetic Predisposition to Disease
  • Hemolytic-Uremic Syndrome / genetics*
  • Hemolytic-Uremic Syndrome / immunology
  • Heterozygote
  • Humans
  • Membrane Cofactor Protein / genetics*
  • Membrane Cofactor Protein / metabolism
  • Mutation*
  • Phenotype
  • Risk Factors
  • Sequence Deletion

Substances

  • CD46 protein, human
  • CFH protein, human
  • Codon, Nonsense
  • Membrane Cofactor Protein
  • Complement C3b
  • Complement Factor H