Schematic diagram of the structure of MCP and depiction of the initial 24 mutations associated with aHUS. MCP is an ∼ 65-kDa type 1 transmembrane glycoprotein. Beginning at the N-terminus, it consists of 4 ∼ 60 amino acid complement control repeats (also called short consensus repeats and occasionally referred to as “Sushi domains”). Modules 1, 2, and 4 each contain one N-glycosylation site. Next is an alternatively spliced region, rich in serines, threonines, and prolines that are sites for O-glycosylation. This is followed by a juxtamembraneous group of 12 amino acids (encoded by a separate exon) of unknown function, a transmembrane hydrophobic domain, a charged intracellular anchor, and the alternatively spliced cytoplasmic tail (tail 1 or 2). The MCP-BC isoform is shown. Mutations associated with aHUS are primarily clustered in the 4 extracellular modules. Mutations associated with reduced expression levels are marked by an asterisk. The mutation in red is S206P, which is discussed in the text. (Used with permission from Richards et al.¹⁵ )