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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) Band 7p13 Start 44,512,535 bp End 44,541,330 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 A1 Start 6,161,013 bp End 6,180,143 bp
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
Wikidata
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Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract's epithelial cells as well as in hepatocytes. Specifically, it appears to bind to a critical mediator of cholesterol absorption.

The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of 15-20%. Polymorphic variations in the NPC1L1 gene could be associated with non-response to ezetimibe treatment. 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.

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.

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

References

1. ^ GRCh38: Ensembl release 89: ENSG00000015520 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000020447 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. (June 2005). "The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8132–7. Bibcode:2005PNAS..102.8132G. doi:10.1073/pnas.0500269102. PMC 1149415. PMID 15928087.
6. Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L (July 2007). "Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe". The Journal of Clinical Investigation. 117 (7): 1968–78. doi:10.1172/JCI30060. PMC 1888567. PMID 17571164.
7. Davis HR, Veltri EP (June 2007). "Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia". Journal of Atherosclerosis and Thrombosis. 14 (3): 99–108. doi:10.5551/jat.14.99. PMID 17587760.
8. Universal protein resource accession number Q9UHC9 for "Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)" at UniProt.
9. Myocardial Infarction Genetics Consortium Investigators; Stitziel, Nathan O.; Won, Hong-Hee; Morrison, Alanna C.; Peloso, Gina M.; Do, Ron; Lange, Leslie A.; Fontanillas, Pierre; Gupta, Namrata; Duga, Stefano; Goel, Anuj; Farrall, Martin; Saleheen, Danish; Ferrario, Paola; König, Inke (2014-11-27). "Inactivating mutations in NPC1L1 and protection from coronary heart disease". The New England Journal of Medicine. 371 (22): 2072–2082. doi:10.1056/NEJMoa1405386. ISSN 1533-4406. PMC 4335708. PMID 25390462.
10. Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (January 2012). "Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor". Nature Medicine. 18 (2): 281–5. doi:10.1038/nm.2581. PMC 3530957. PMID 22231557.
11. Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. (SEAS Investigators) (September 2008). "Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis". The New England Journal of Medicine. 359 (13): 1343–56. doi:10.1056/NEJMoa0804602. PMID 18765433.
12. Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R (September 2008). "Analyses of cancer data from three ezetimibe trials". The New England Journal of Medicine. 359 (13): 1357–66. doi:10.1056/NEJMsa0806603. PMID 18765432.
13. Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P (December 2015). "Safety and efficacy of ezetimibe: A meta-analysis". International Journal of Cardiology. 201: 247–52. doi:10.1016/j.ijcard.2015.08.103. PMID 26301648.

External links

• NPC1L1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q9UHC9 (Human NPC1-like intracellular cholesterol transporter 1) at the PDBe-KB.

• Genes on human chromosome 7