PCSK9 Mutations

PCSK9 gene mutations can have profound effects on plasma LDL-C levels1

PCSK9 Loss of Function Mutations

Increase LDLR levels on the surface of the hepatocyte, which leads to an increase in LDL clearance, resulting in low plasma LDL-C levels2,3

PCSK9 Gain of Function Mutations

Decrease LDLR levels on the surface of the hepatocyte, which leads to a reduction in LDL clearance, resulting in high plasma LDL-C levels2,3

PCSK9 FunctionPCSK9 Function
LDLR Surface ExpressionLDLR Surface Expression
Plasma LDL-C LevelsPlasma LDL-C Levels
LDL
LDL
LDL
LDL
LDL
LDL
LDL
LDL
LDL
LDL
LDL
PCSK9
PCSK9
Blood
LDL
LDL
LDL
PCSK9
PCSK9
Blood
Learn more about PCSK9 mutations

Learn more about PCSK9 mutations

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Individuals with PCSK9 loss-of-function mutations display low LDL-C levels, whereas those with gain-of-function mutations display increased plasma LDL-C levels1


What is the relationship between HMG-CoA, LDLRs, and PCSK9?

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HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LDL = low-density lipoprotein; LDL-C = low-density lipoprotein cholesterol; LDLR = low-density lipoprotein receptor; PCSK9 = proprotein convertase subtilisin/kexin type 9.

References

  1. Horton JD, Cohen JC, Hobbs HH. J Lipid Res. 2009;50(suppl):S172-S177.
  2. Abifadel M, Rabes J-P, Devilliers M, et al. Hum Mutat. 2009;30:520-529.
  3. Steinberg D, Witzum JL. PNAS. 2009;106:9546-9547.