“…PCSK9 is highly conserved among mammals, including chimpanzee, monkey, camel, alpaca, rat, and mouse, with an approximate amino acid identity of 99, 96, 82, 81, 77, and 77%, respectively. The majority of identified gain-of-function and loss-of-function mutations occur in entirely conserved residues, such as gain-of-function mutations D35Y, L108R, S127R, D129G, N157K, R215H, F216L, R218S, A220T, R357H, D374Y, N425S, R468W, R496W and R499H, and lossof-function mutations R104C, R105Q, G106R, G236S, L253F, G316C, N354I and S462P (2, 4,11,12). However, loss-of-function mutations R46L and R93C and gain-of-function mutations R96L, A168E, R499H, and S636R are not conserved between human and mouse or rat PCSK9.…”