NPC1L1
NPC1 like intracellular cholesterol transporter 1
Gene Information Card
| Symbol | NPC1L1 |
|---|---|
| Full Name | NPC1 like intracellular cholesterol transporter 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p13 |
| NCBI Gene ID | 29881 ncbi.nlm.nih.gov/gene/29881 |
| Ensembl ID | ENSG00000115594 |
| UniProt ID | Q9UHC9 |
| OMIM ID | 608010 |
| HGNC ID | 7898 |
| Aliases | NPC1L1, NPC1L1, SLC65A2 |
Description
NPC1L1 (NPC1 like intracellular cholesterol transporter 1) encodes a multi-pass transmembrane protein that plays a critical role in intestinal cholesterol absorption and hepatic cholesterol reuptake. It is the molecular target of the cholesterol-lowering drug ezetimibe. The protein localizes to the brush border membrane of enterocytes and the canalicular membrane of hepatocytes, where it facilitates the uptake of dietary and biliary cholesterol. Loss-of-function variants are associated with reduced cholesterol absorption and lower plasma LDL-cholesterol levels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypercholesterolemia, susceptibility to | Reduced function of NPC1L1 decreases intestinal cholesterol absorption, lowering LDL-C levels. | ClinVar, OMIM |
| Sitosterolemia (indirect) | NPC1L1 mediates plant sterol absorption; variants may contribute to sterol accumulation. | OMIM |
| Non-alcoholic fatty liver disease (NAFLD) | Altered NPC1L1 expression influences hepatic cholesterol accumulation. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 45.2 | High |
| Liver | 12.8 | Medium |
| Gallbladder | 8.5 | Medium |
| Pancreas | 3.1 | Low |
| Kidney | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | 32.5 | Intestinal epithelial cell line, high expression |
| HepG2 | 15.3 | Hepatocellular carcinoma cell line, moderate expression |
| HeLa | 0.8 | Cervical cancer cell line, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1679C>T (p.Thr560Met) | missense | 0.1% (gnomAD) | Reduced cholesterol uptake; associated with lower LDL-C |
| c.2534A>G (p.Asn845Ser) | missense | 0.05% | Decreased ezetimibe binding affinity |
| c.2920C>T (p.Arg974*) | nonsense | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense variants that impair cholesterol transport or protein stability.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • cholesterol transport | • sterol uptake |
| • plasma membrane | • integral component of membrane |
| • receptor-mediated endocytosis |
Pathways
• Cholesterol metabolism (Reactome: R-HSA-191273)
• Intestinal cholesterol absorption (KEGG: hsa04979)
Protein Summary
NPC1L1 is a 1359-amino-acid transmembrane protein with 13 transmembrane domains, a sterol-sensing domain, and multiple N-linked glycosylation sites. It functions as a sterol transporter, mediating the uptake of cholesterol and plant sterols into enterocytes. The protein undergoes clathrin-mediated endocytosis upon sterol binding and is the pharmacological target of ezetimibe, which inhibits cholesterol absorption.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPC1L1 Knockout HEK293 Cell Line | EDJ-KQ3813 | Human | 29881 | 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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