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The PCSK9 gene at 1p32.3 codes for the precursor 692 amino acid peptide to proprotein convertase 9 (Proprotein convertase subtilisin/kexin type 9). This serine protease is key to the degradation of low-density lipid receptor proteins so regulating plasma cholesterol. It is active on:

It inhibits intracellular degradation of apolipoprotein B-100 via the autophagosome/lysosome pathway as well as regulating neuronal apoptosis via modulation of apolipoprotein receptor 2 levels. With in the cell its processing depends upon autocatalytic cleavage so as to transport it from the endoplasmic reticulum to the Golgi apparatus and for its secretion. In the absence of LDLR it stays in the endoplasmic reticulum but colocalizes to the cell surface and to the endosomes/lysosomes if LDLR is present. This then allows LDLR degradation.

It is targeted by the monoclonal antibodies alirocumab and evolocumab. These may be useful as inhibition of HMGCoA reductase by statins upregulates PCSK9 limiting their effectiveness[1].

Variations in the PCSK9gene which is close by the APOA2 gene are associated with:


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