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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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 |
6.45 |
| Passage Frozen |
13 |
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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 |
W833X; NIEMANN-PICK DISEASE, TYPE C1 |
| Identified Mutation |
TRP833TER |
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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; fibroblasts showed 67 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. Hum Mut 22:313-325 (2003)]; fibroblasts were scored as "NA" in a filipin staining assay (see Park et al., 2003); the donor subject is a compound heterozygote at the NPC1 gene locus: allele 1 carries a substitution (G>A) at nucleotide 2498 (c.2498G>A) in exon 16, resulting in a nonsense mutation at codon 833 [W833X (TRP833TER)]; allele 2 carries a substitution (T>C) at nucleotide 3182 (c.3182T>C) in exon 21, resulting in a missense mutation at codon 1061 [I1061T (ILE1061THR)]; the subject also carries the following polymorphism: (G>A) at nucleotide 3797 (3797G>A) resulting in a missense mutation (R>Q) at codon 1266 [R1266Q (ARG1266GLN]; the first nucleotide of the initiating MET codon is numbered +1. |
| Flint M, Chatterjee P, Lin DL, McMullan LK, Shrivastava-Ranjan P, Bergeron É, Lo MK, Welch SR, Nichol ST, Tai AW, Spiropoulou CF, A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus Nature communications10:285 2018 |
| PubMed ID: 30655525 |
| Passage Frozen |
13 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Supplement |
- |
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