NPC1 Gene: Niemann-Pick Disease Type C1
A comprehensive biomedical overview of the NPC1 gene, its function, associated diseases, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | NPC1 |
|---|---|
| Full Name | NPC intracellular cholesterol transporter 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 18q11.2 |
| NCBI Gene ID | 4864 ncbi.nlm.nih.gov/gene/4864 |
| Ensembl ID | ENSG00000141458 |
| UniProt ID | O15118 |
| OMIM ID | 607623 |
| HGNC ID | 7897 |
| Aliases | NPC, SLC65A1, Niemann-Pick disease, type C1 |
Description
The NPC1 gene encodes a large transmembrane protein that resides in the late endosome/lysosome and is essential for the intracellular trafficking of cholesterol and lipids. Mutations in NPC1 cause Niemann-Pick disease type C1 (NPC1), an autosomal recessive lysosomal storage disorder characterized by progressive neurodegeneration and hepatosplenomegaly. The protein functions in concert with NPC2 to mediate cholesterol export from lysosomes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Niemann-Pick disease type C1 (NPC1) | Loss-of-function mutations in NPC1 impair cholesterol and lipid trafficking, leading to lysosomal accumulation of unesterified cholesterol and glycosphingolipids. | OMIM 257220; ClinVar; multiple publications |
| Niemann-Pick disease type C (broader phenotype) | NPC1 mutations account for ~95% of NPC cases; the remainder are due to NPC2 mutations. | OMIM; GeneReviews |
| Hepatocellular carcinoma (potential association) | Altered NPC1 expression may affect cholesterol homeostasis and tumor progression, but evidence is preliminary. | COSMIC; limited studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Brain | 8.5 | Medium |
| Lung | 6.3 | Low |
| Kidney | 5.1 | Low |
| Spleen | 7.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 12.4 | Liver cancer cell line; high expression |
| SH-SY5Y | 9.8 | Neuroblastoma; moderate expression |
| A549 | 7.2 | Lung carcinoma; moderate |
| HeLa | 6.5 | Cervical carcinoma; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3182T>C (p.I1061T) | Missense | ~15-20% of NPC1 alleles in Western populations | Common pathogenic variant; causes protein misfolding and reduced function |
| c.3019C>T (p.R1007C) | Missense | Rare | Pathogenic; disrupts sterol-sensing domain |
| c.3599A>G (p.N1200S) | Missense | Rare | Pathogenic; affects protein stability |
| c.1628delC (frameshift) | Frameshift | Rare | Loss-of-function; leads to truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most NPC1 mutations are loss-of-function, leading to impaired cholesterol export from lysosomes. This results in lysosomal lipid accumulation and cellular dysfunction.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NPC1; all known pathogenic variants are loss-of-function.
Dominant Negative (DN)
NPC1 is autosomal recessive; no dominant-negative effects are documented. Heterozygous carriers are typically asymptomatic.
View complete mutation data：
Gene Ontology (GO)
| • cholesterol binding | • lipid transporter activity |
| • sterol transporter activity | • late endosome membrane |
| • lysosomal membrane | • cholesterol homeostasis |
| • intracellular cholesterol transport | • response to sterol depletion |
Pathways
• Cholesterol metabolism
• Sphingolipid metabolism
• Lysosomal transport
• NPC1/NPC2-mediated cholesterol transport
Protein Summary
The NPC1 protein is a 1278-amino-acid glycoprotein with 13 transmembrane domains, a sterol-sensing domain, and a luminal N-terminal domain that binds cholesterol. It localizes to late endosomes/lysosomes and interacts with NPC2 to facilitate cholesterol egress. Mutations cause Niemann-Pick type C1, a neurodegenerative lysosomal storage disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPC1 Knockout HEK293T Cell Line | EDJ-KQ240 | Human | 4864 | Details Get a Quote |
| NPC1L1 Knockout HEK293 Cell Line | EDJ-KQ3813 | Human | 29881 | Details Get a Quote |
| NPC1 Knockout HEK293 Cell Line | EDJ-KQ14457 | Human | 4864 | Details Get a Quote |
| NPC1 Knockout HCT 116 Cell Line | EDJ-KQ44689 | Human | 4864 | Details Get a Quote |
| NPC1 Knockout HeLa Cell Line | EDJ-KQ44690 | Human | 4864 | Details Get a Quote |
| NPC1 Knockout A-549 Cell Line | EDJ-KQ43431 | Human | 4864 | Details Get a Quote |
| NPC1L1 Knockout HeLa Cell Line | EDJ-KQ56115 | Human | 29881 | Details Get a Quote |
| NPC1L1 Knockout A-549 Cell Line | EDC08212 | Human | 29881 | Details Get a Quote |
| NPC1L1 Knockout HCT 116 Cell Line | EDJ-KQ73053 | Human | 29881 | Details Get a Quote |
| NPC1L1 Knockout Huh-7 Cell Line | EDC08353 | Human | 29881 | Details Get a Quote |
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