NPC1L1

Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract's epithelial cells^[5] as well as in hepatocytes.^[6] Specifically, it appears to bind to a critical mediator of cholesterol absorption.

NPC1L1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3QNT
Identifiers
Aliases	NPC1L1, NPC11L1, NPC1 like intracellular cholesterol transporter 1, SLC65A2, LDLCQ7
External IDs	OMIM: 608010; MGI: 2685089; HomoloGene: 56585; GeneCards: NPC1L1; OMA:NPC1L1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p13 Start 44,512,535 bp[1] End 44,541,330 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A1 Start 6,161,013 bp[2] End 6,180,143 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa duodenum right lobe of liver testicle islet of Langerhans gallbladder muscle layer of sigmoid colon right coronary artery Descending thoracic aorta popliteal artery Top expressed in epithelium of small intestine jejunum ileum duodenum migratory enteric neural crest cell embryo Paneth cell morula blastocyst yolk sac More reference expression data BioGPS n/a
Gene ontology Molecular function myosin V binding protein binding Cellular component membrane plasma membrane brush border membrane apical plasma membrane cytoplasmic vesicle membrane cytoplasmic vesicle integral component of membrane spanning component of plasma membrane Biological process lipoprotein metabolic process steroid metabolic process lipid metabolism cholesterol transport cholesterol metabolic process intestinal cholesterol absorption cholesterol biosynthetic process intestinal lipid absorption cellular response to sterol depletion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 29881 237636 Ensembl ENSG00000015520 ENSMUSG00000020447 UniProt Q9UHC9 Q6T3U4 RefSeq (mRNA) NM_001101648 NM_001300967 NM_013389 NM_207242 RefSeq (protein) NP_001095118 NP_001287896 NP_037521 n/a Location (UCSC) Chr 7: 44.51 – 44.54 Mb Chr 11: 6.16 – 6.18 Mb PubMed search [3] [4]
Wikidata
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The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of 15-20%.^[7] Polymorphic variations in the NPC1L1 gene could be associated with non-response to ezetimibe treatment.^[8] One study found that people with inactivating mutations in the NPC1L1 gene had a lower LDL cholesterol level, as well as an around 50% reduction in the risk of coronary heart disease.^[9]

NPC1L1 has been shown to be an accessory receptor for hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy.^[10]

As cancer appeared more frequently in patients treated with simvastatin-ezetimibe combination therapy in one clinical trial,^[11] it had been hypothesized that NPC1L1 inhibition by ezetimibe might be associated with an increased cancer risk.^[12] However, a meta-analysis of ezetimibe clinical data showed no increase in the risk of cancer from treatment with ezetimibe.^[13]