Mutations in PCSK9 Cause Autosomal Dominant Hypercholesterolemia

Nat Genet. 2003 Jun;34(2):154-6. doi: 10.1038/ng1161.

Abstract

Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Chromosomes, Human, Pair 1 / genetics
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Humans
  • Hyperlipoproteinemia Type II / enzymology
  • Hyperlipoproteinemia Type II / genetics*
  • Liver / enzymology
  • Male
  • Mutation*
  • Pedigree
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases / genetics*

Substances

  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases

Associated data

  • OMIM/144400
  • OMIM/176000
  • OMIM/603776