title: Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
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.
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Carstea
authors.forename: J A
authors.initials: JA
authors.lastname: Morris
authors.forename: K G
authors.initials: KG
authors.lastname: Coleman
authors.forename: S K
authors.initials: SK
authors.lastname: Loftus
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Cummings
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: M A
authors.initials: MA
authors.lastname: Rosenfeld
authors.forename: W J
authors.initials: WJ
authors.lastname: Pavan
authors.forename: D B
authors.initials: DB
authors.lastname: Krizman
authors.forename: J
authors.initials: J
authors.lastname: Nagle
authors.forename: M H
authors.initials: MH
authors.lastname: Polymeropoulos
authors.forename: S L
authors.initials: SL
authors.lastname: Sturley
authors.forename: Y A
authors.initials: YA
authors.lastname: Ioannou
authors.forename: M E
authors.initials: ME
authors.lastname: Higgins
authors.forename: M
authors.initials: M
authors.lastname: Comly
authors.forename: A
authors.initials: A
authors.lastname: Cooney
authors.forename: A
authors.initials: A
authors.lastname: Brown
authors.forename: C R
authors.initials: CR
authors.lastname: Kaneski
authors.forename: E J
authors.initials: EJ
authors.lastname: Blanchette-Mackie
authors.forename: N K
authors.initials: NK
authors.lastname: Dwyer
authors.forename: E B
authors.initials: EB
authors.lastname: Neufeld
authors.forename: T Y
authors.initials: TY
authors.lastname: Chang
authors.forename: L
authors.initials: L
authors.lastname: Liscum
authors.forename: J F
authors.initials: JF
authors.lastname: Strauss
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Zeigler
authors.forename: R
authors.initials: R
authors.lastname: Carmi
authors.forename: J
authors.initials: J
authors.lastname: Sokol
authors.forename: D
authors.initials: D
authors.lastname: Markie
authors.forename: R R
authors.initials: RR
authors.lastname: O'Neill
authors.forename: O P
authors.initials: OP
authors.lastname: van Diggelen
authors.forename: M
authors.initials: M
authors.lastname: Elleder
authors.forename: M C
authors.initials: MC
authors.lastname: Patterson
authors.forename: R O
authors.initials: RO
authors.lastname: Brady
authors.forename: M T
authors.initials: MT
authors.lastname: Vanier
authors.forename: P G
authors.initials: PG
authors.lastname: Pentchev
authors.forename: D A
authors.initials: DA
authors.lastname: Tagle
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D006706:Homeostasis; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry; D019476:Insect Proteins / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D008078:Cholesterol, LDL; D029721:Drosophila Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011506:Proteins; D011956:Receptors, Cell Surface; C102196:SREBP cleavage-activating protein; C070844:ptc protein, Drosophila; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases