NPC2 Gene: Niemann-Pick Disease, Type C2
NPC2 encodes a cholesterol-binding protein essential for intracellular lipid trafficking; mutations cause Niemann-Pick disease type C2.
Gene Information Card
| Symbol | NPC2 |
|---|---|
| Full Name | NPC intracellular cholesterol transporter 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 10577 ncbi.nlm.nih.gov/gene/10577 |
| Ensembl ID | ENSG00000119655 |
| UniProt ID | P61916 |
| OMIM ID | 601015 |
| HGNC ID | 7897 |
| Aliases | HE1, EPC2, NP-C2 |
Description
NPC2 (NPC intracellular cholesterol transporter 2) encodes a small soluble lysosomal protein that binds cholesterol with high affinity and facilitates its egress from lysosomes. It functions cooperatively with NPC1 to mediate the export of unesterified cholesterol and other lipids. Loss-of-function mutations in NPC2 cause Niemann-Pick disease type C2 (NPC2), a rare autosomal recessive lysosomal storage disorder characterized by progressive neurodegeneration, hepatosplenomegaly, and accumulation of cholesterol and glycosphingolipids in lysosomes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Niemann-Pick disease type C2 | Loss-of-function mutations in NPC2 impair cholesterol transport from lysosomes, leading to lysosomal lipid accumulation and cellular dysfunction. | ClinVar, OMIM |
| Niemann-Pick disease type C (general) | NPC2 mutations account for approximately 5% of NPC cases; the remaining 95% are due to NPC1 mutations. Both genes are required for normal cholesterol egress. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 24.3 | High |
| Liver | 18.7 | High |
| Spleen | 16.2 | High |
| Kidney | 12.1 | Medium |
| Brain | 8.5 | Medium |
| Heart | 6.3 | Medium |
| Pancreas | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 22.4 | Hepatocellular carcinoma cell line |
| A549 | 19.8 | Lung adenocarcinoma cell line |
| K-562 | 15.6 | Chronic myelogenous leukemia cell line |
| SH-SY5Y | 10.2 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.58G>T (p.Glu20*) | Nonsense | Rare | Premature stop codon; loss of protein function; associated with NPC2 disease. |
| c.140C>T (p.Pro47Leu) | Missense | Rare | Reduced cholesterol binding affinity; pathogenic in NPC2. |
| c.199C>T (p.Arg67Cys) | Missense | Rare | Impaired secretion and lysosomal targeting; pathogenic. |
| c.441+1G>A | Splice site | Rare | Exon skipping; frameshift and loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most NPC2 mutations are loss-of-function, leading to reduced or absent cholesterol-binding activity and lysosomal lipid accumulation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NPC2.
Dominant Negative (DN)
No dominant-negative effects described; NPC2 disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • cholesterol binding (GO:0005543) | • lysosome (GO:0005764) |
| • cholesterol transport (GO:0015485) | • cholesterol homeostasis (GO:0030301) |
| • extracellular space (GO:0005615) |
Pathways
• Intracellular cholesterol transport (NPC1/NPC2 pathway)
• Lysosomal lipid degradation
Protein Summary
NPC2 is a 151-amino-acid soluble glycoprotein (UniProt P61916) localized primarily to the lysosomal lumen. It contains a cholesterol-binding pocket formed by a beta-sandwich fold. NPC2 binds cholesterol with high affinity and transfers it to the N-terminal domain of NPC1 for export from lysosomes. The protein is also secreted into various body fluids, including plasma, milk, and epididymal fluid, where it may play roles in extracellular cholesterol transport. Deficiency leads to lysosomal cholesterol accumulation characteristic of Niemann-Pick disease type C2.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPC2 Knockout HEK293 Cell Line | EDJ-KQ3169 | Human | 10577 | Details Get a Quote |
| NPC2 Knockout A-549 Cell Line | EDJ-KQ24585 | Human | 10577 | Details Get a Quote |
| NPC2 Knockout HCT 116 Cell Line | EDJ-KQ24586 | Human | 10577 | Details Get a Quote |
| NPC2 Knockout HeLa Cell Line | EDJ-KQ24587 | Human | 10577 | Details Get a Quote |
