Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis

Science. 1997 Jul 11;277(5323):228-31. doi: 10.1126/science.277.5323.228.

Abstract

Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)-derived cholesterol. By positional cloning methods, a gene (NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278-amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins*
  • Cholesterol / metabolism*
  • Cholesterol, LDL / metabolism
  • Chromosome Mapping
  • Chromosomes, Human, Pair 18
  • Cloning, Molecular
  • Drosophila Proteins*
  • Homeostasis
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / chemistry
  • Insect Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins
  • Lysosomes / metabolism
  • Membrane Glycoproteins*
  • Membrane Proteins / chemistry
  • Molecular Sequence Data
  • Mutation
  • Niemann-Pick C1 Protein
  • Niemann-Pick Diseases / genetics*
  • Niemann-Pick Diseases / metabolism
  • Polymorphism, Single-Stranded Conformational
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / physiology
  • Receptors, Cell Surface / chemistry
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • Carrier Proteins
  • Cholesterol, LDL
  • Drosophila Proteins
  • Insect Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • NPC1 protein, human
  • Niemann-Pick C1 Protein
  • Proteins
  • Receptors, Cell Surface
  • SREBP cleavage-activating protein
  • ptc protein, Drosophila
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases

Associated data

  • GENBANK/AF002020
  • GENBANK/M11058
  • GENBANK/U33335
  • GENBANK/U53340
  • GENBANK/U59464
  • GENBANK/U67060