Proprotein convertase subtilisin kexin 9: the third locus implicated in autosomal dominant hypercholesterolemia

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Updated: Aug 19, 2026

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
08:14

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9

Published on: August 28, 2018

Kara N Maxwell1, Jan L Breslow

  • 1Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021, USA.

Current Opinion in Lipidology
|March 16, 2005
PubMed

Insights

Proprotein convertase subtilisin kexin 9 (PCSK9) mutations cause autosomal dominant hypercholesterolemia (HCHOLA3). PCSK9 regulates LDL receptor levels, offering new targets for cholesterol-lowering drugs.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cardiovascular Disease

Background:

  • Autosomal dominant hypercholesterolemia (ADHD) is a genetic disorder characterized by high LDL cholesterol and early atherosclerosis.
  • Mutations in LDL receptor and apolipoprotein B genes are known causes of ADHD.
  • Recent studies identified families with ADHD phenotypes but without mutations in known genes.

Purpose of the Study:

  • To identify novel genes responsible for autosomal dominant hypercholesterolemia.
  • To gain further insights into LDL metabolism and receptor-mediated endocytosis.
  • To understand the genetic basis of ADHD in families without known mutations.

Main Methods:

  • Microarray analysis
  • Database searches
  • Genetic linkage studies (implied)
  • Functional studies of PCSK9 (implied)

Main Results:

  • A novel gene, proprotein convertase subtilisin kexin 9 (PCSK9), was identified.
  • Missense mutations in PCSK9 were found in families with autosomal dominant hypercholesterolemia (HCHOLA3).
  • PCSK9 was demonstrated to play a role in regulating LDL receptor protein levels.

Conclusions:

  • PCSK9 is the third identified genetic locus for autosomal dominant hypercholesterolemia (HCHOLA3).
  • PCSK9 plays a significant role in cellular cholesterol metabolism.
  • Understanding PCSK9 function may lead to new treatments for hypercholesterolemia.
Abstract

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