Description:
NIEMANN-PICK DISEASE, TYPE C1; NPC1
NPC1 GENE; NPC1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Lipid Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Molecular characterization before cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
4.37 |
| Passage Frozen |
7 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| Gene |
NPC1 |
| Chromosomal Location |
18q11-q12 |
| Allelic Variant 1 |
607623.0010; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
ILE1061THR; In an initial study of 25 patients with type C1 Niemann-Pick disease, Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] identified a T-to-C transition at nucleotide 3182 of the NPC1 gene that led to an ile1061-to-thr substitution (I1061T) in 3 patients. The mutation, located in exon 21, affected a putative transmembrane domain of the protein. The mutation was particularly frequent in patients with NPC from western Europe, especially France and the U.K. and in Hispanic patients whose roots were in the Upper Rio Grande valley of the U.S. Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] concluded that the I1061T mutation originated in Europe and that the high frequency in northern Rio Grande Hispanics resulted from a founder effect. |
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| Gene |
NPC1 |
| Chromosomal Location |
18q11-q12 |
| Allelic Variant 2 |
607623.0010; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
ILE1061THR; In an initial study of 25 patients with type C1 Niemann-Pick disease, Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] identified a T-to-C transition at nucleotide 3182 of the NPC1 gene that led to an ile1061-to-thr substitution (I1061T) in 3 patients. The mutation, located in exon 21, affected a putative transmembrane domain of the protein. The mutation was particularly frequent in patients with NPC from western Europe, especially France and the U.K. and in Hispanic patients whose roots were in the Upper Rio Grande valley of the U.S. Millat et al. [Am. J. Hum. Genet. 65: 1321-1329 (1999)] concluded that the I1061T mutation originated in Europe and that the high frequency in northern Rio Grande Hispanics resulted from a founder effect. |
| Remarks |
Clinically affected; the donor subject is homozygous at the NPC1 gene locus: alleles 1 & 2 carry a substitution (T>C) at nucleotide 3182 (c.3182T>C) in exon 21, resulting in a missense mutation at codon 1061 [ I1061T (ILE1061THR); the first nucleotide of the initiating Met codon is numbered +1; fibroblasts showed 533 pmol CE/mg protein/6 hr activity in a cholesterol esterification assay (normal mean was 1855 +/- 1327 pmol CE/mg protein/6 hr, see Park et al., 2003). |
| Azaria RD, Correia AB, Schache KJ, Zapata M, Pathmasiri KC, Mohanty V, Nannapaneni DT, Ashfeld BL, Helquist P, Wiest O, Ohgane K, Li Q, Fredenburg RA, Blagg BS, Cologna SM, Schultz ML, Lieberman AP, Mutant induced neurons and humanized mice enable identification of Niemann-Pick C1 proteostatic therapies JCI insight: 2024 |
| PubMed ID: 39207850 |
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| Chen J, Cazenave-Gassiot A, Xu Y, Piroli P, Hwang R, DeFreitas L, Chan RB, Di Paolo G, Nandakumar R, Wenk MR, Marquer C, Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate Communications biology6:210 2022 |
| PubMed ID: 36823305 |
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| Liedtke M, Völkner C, Hermann A, Frech MJ, Impact of Organelle Transport Deficits on Mitophagy and Autophagy in Niemann-Pick Disease Type C Cells11:210 2022 |
| PubMed ID: 35159316 |
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| Schultz ML, Schache KJ, Azaria RD, Kuiper EQ, Erwood S, Ivakine EA, Farhat NY, Porter FD, Pathmasiri KC, Cologna SM, Uhler MD, Lieberman AP, Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease JCI insight7:210 2022 |
| PubMed ID: 36301667 |
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| Stahl-Meyer K, Bilgin M, Holland LKK, Stahl-Meyer J, Kirkegaard T, Petersen NHT, Maeda K, Jäättelä M, Galactosyl- and glucosylsphingosine induce lysosomal membrane permeabilization and cell death in cancer cells PloS one17:e0277058 2022 |
| PubMed ID: 36409725 |
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| Kang I, Yoo JM, Kim D, Kim J, Cho MK, Lee SE, Kim DJ, Lee BC, Lee JY, Kim JJ, Shin N, Choi SW, Lee YH, Ko HS, Shin S, Hong BH, Kang KS, Graphene Quantum Dots Alleviate Impaired Functions in Niemann-Pick Disease Type C in Vivo Nano letters21:2339-2346 2021 |
| PubMed ID: 33472003 |
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| Kutchukian C, Vivas O, Casas M, Jones JG, Tiscione SA, Simó S, Ory DS, Dixon RE, Dickson EJ, NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes The EMBO journal21:e105990 2021 |
| PubMed ID: 34019311 |
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| Völkner C, Pantoom S, Liedtke M, Lukas J, Hermann A, Frech MJ, Assessment of FDA-Approved Drugs as a Therapeutic Approach for Niemann-Pick Disease Type C1 Using Patient-Specific iPSC-Based Model Systems Cells11:e105990 2021 |
| PubMed ID: 35159129 |
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| Hong S, Lee SE, Kang I, Yang J, Kim H, Kim J, Kang KS, Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice Journal of veterinary science22:e7 2020 |
| PubMed ID: 33522159 |
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| Lee SE, Shin N, Kook MG, Kong D, Kim NG, Choi SW, Kang KS, Human iNSC-derived brain organoid model of lysosomal storage disorder in Niemann-Pick disease type C Cell death & disease11:1059 2020 |
| PubMed ID: 33311479 |
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| Li R, Pradhan M, Xu M, Roeder A, Beers J, Zou J, Liu C, Porter FD, Zheng W, An induced pluripotent stem cell line (TRNDi001-D) from a Niemann-Pick disease type C1 (NPC1) patient carrying a homozygous p I1061T (c 3182T>C) mutation in the NPC1 gene Stem cell research44:101737 2020 |
| PubMed ID: 32114296 |
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| Liu EA, Schultz ML, Mochida C, Chung C, Paulson HL, Lieberman AP, Fbxo2 mediates clearance of damaged lysosomes and modifies neurodegeneration in the Niemann-Pick C brain JCI insight44:101737 2020 |
| PubMed ID: 32931479 |
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| Shioi R, Karaki F, Yoshioka H, Noguchi-Yachide T, Ishikawa M, Dodo K, Hashimoto Y, Sodeoka M, Ohgane K, Image-based screen capturing misfolding status of Niemann-Pick type C1 identifies potential candidates for chaperone drugs PloS one15:e0243746 2020 |
| PubMed ID: 33315900 |
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| Subramanian K, Hutt DM, Scott SM, Gupta V, Mao S, Balch WE, Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid The Journal of biological chemistry15:e0243746 2020 |
| PubMed ID: 32354745 |
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| Gupta A, Rivera-Molina F, Xi Z, Toomre D, Schepartz A, Endosome motility defects revealed at super-resolution in live cells using HIDE probes Nature chemical biology15:e0243746 2019 |
| PubMed ID: 32094922 |
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| Schultz ML, Fawaz MV, Azaria RD, Hollon TC, Liu EA, Kunkel TJ, Halseth TA, Krus KL, Ming R, Morin EE, McLoughlin HS, Bushart DD, Paulson HL, Shakkottai VG, Orringer DA, Schwendeman AS, Lieberman AP, Synthetic high-density lipoprotein nanoparticles for the treatment of Niemann-Pick diseases BMC medicine17:200 2019 |
| PubMed ID: 31711490 |
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| Tiscione SA, Vivas O, Ginsburg KS, Bers DM, Ory DS, Santana LF, Dixon RE, Dickson EJ, Disease-associated mutations in Niemann-Pick type C1 alter ER calcium signaling and neuronal plasticity The Journal of cell biology17:200 2019 |
| PubMed ID: 31601621 |
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| Vivas O, Tiscione SA, Dixon RE, Ory DS, Dickson EJ, Niemann-Pick Type C Disease Reveals a Link between Lysosomal Cholesterol and PtdIns(4,5)P Cell reports27:2636-2648.e4 2018 |
| PubMed ID: 31141688 |
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| Wang C, Scott SM, Subramanian K, Loguercio S, Zhao P, Hutt DM, Farhat NY, Porter FD, Balch WE, Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process Nature communications10:5052 2018 |
| PubMed ID: 31699992 |
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| Zhang X, Chen W, Gao Q, Yang J, Yan X, Zhao H, Su L, Yang M, Gao C, Yao Y, Inoki K, Li D, Shao R, Wang S, Sahoo N, Kudo F, Eguchi T, Ruan B, Xu H, Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR PLoS biology17:e3000252 2018 |
| PubMed ID: 31112550 |
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| Pugach EK, Feltes M, Kaufman RJ, Ory DS, Bang AG, High-content screen for modifiers of Niemann-Pick type C disease in patient cells Human molecular genetics27:2101-2112 2017 |
| PubMed ID: 29659804 |
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| Schultz ML, Krus KL, Kaushik S, Dang D, Chopra R, Qi L, Shakkottai VG, Cuervo AM, Lieberman AP, Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD Nature communications9:3671 2017 |
| PubMed ID: 30202070 |
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| Maetzel D, Sarkar S, Wang H, Abi-Mosleh L, Xu P, Cheng AW, Gao Q, Mitalipova M, Jaenisch R, Genetic and chemical correction of cholesterol accumulation and impaired autophagy in hepatic and neural cells derived from Niemann-Pick Type C patient-specific iPS cells Stem cell reports2:866-80 2014 |
| PubMed ID: 24936472 |
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| Ohgane K, Karaki F, Dodo K, Hashimoto Y, Discovery of Oxysterol-Derived Pharmacological Chaperones for NPC1: Implication for the Existence of Second Sterol-Binding Site Chemistry & biology20:391-402 2012 |
| PubMed ID: 23521797 |
| Passage Frozen |
7 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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