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.

Pathology

 mutations of the CD46 gene in atypical hemolytic uremic syndrome (HUS)

• heterozygous deletion resulting in the intracellular retention of the mutant protein
• different heterozygous deletion leading to a premature stop codon and the loss of the C-terminus
• substitution (S206P) resulting in cell-surface expression but inefficient inactivation of surface-bound C3b

Features

 factor-H mutations in 15-30% of patients with atypical hemolytic uremic syndrome (HUS)

References

 Gill DB, Atkinson JP. CD46 in Neisseria pathogenesis. Trends Mol Med. 2004 Sep;10(9):459-65. PMID: #15350899#

 Goodship TH, Liszewski MK, Kemp EJ, Richards A, Atkinson JP. Mutations in CD46, a complement regulatory protein, predispose to atypical HUS. Trends Mol Med. 2004 May 1;10(5):226-231. PMID: #15121049#