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


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.


Carstea, E D; Morris, J A; Coleman, K G; Loftus, S K; Zhang, D; Cummings, C; Gu, J; Rosenfeld, M A; Pavan, W J; Krizman, D B; Nagle, J; Polymeropoulos, M H; Sturley, S L; Ioannou, Y A; Higgins, M E; Comly, M; Cooney, A; Brown, A; Kaneski, C R; Blanchette-Mackie, E J; Dwyer, N K; Neufeld, E B; Chang, Soju; Liscum, L; Strauss, J F; Ohno, K; Zeigler, M; Carmi, R; Sokol, J; Markie, D; O'Neill, R R; van Diggelen, O P; Elleder, M; Patterson, M C; Brady, R O; Vanier, M T; Pentchev, P G; Tagle, Danilo;


  • 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 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

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