NPC1 Gene

Name	Niemann-Pick disease, type C1
Description	This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNPC1 functions as an essential endosomal receptor that is hijacked by filoviruses such as Ebola and Marburg to gain entry into host cells. Following proteolytic cleavage of the viral glycoprotein in the endosome, NPC1 directly engages the processed glycoprotein to trigger membrane fusion and promote viral escape into the cytoplasm. This receptor activity is independent of NPC1’s role in cholesterol transport yet is critical for efficient infection by these deadly viruses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn its canonical role, NPC1 is a large, multispanning lysosomal membrane protein that governs the egress of LDL‐derived cholesterol from late endosomes and lysosomes. Together with its soluble partner NPC2, NPC1 accepts cholesterol released by lysosomal hydrolysis and facilitates its “hand‐off” via a network of intricately structured domains—including a luminal cholesterol binding pocket, a sterol‐sensing domain, and a defined intramolecular tunnel—to deliver cholesterol to other cellular compartments. Photoaffinity labeling and high‐resolution structural studies have demonstrated that NPC1 directly binds cholesterol and analogs; conformational changes in its domains (often pH dependent) underlie the directional transfer of cholesterol. Moreover, NPC1 participates in membrane contact site formation with the endoplasmic reticulum—via interactions with proteins such as Gramd1b—and even influences plasma membrane cholesterol distribution by mediating transfer across the lysosomal glycocalyx."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in NPC1 disrupt its normal function and lead to Niemann–Pick type C disease, a fatal neurodegenerative disorder characterized by lysosomal cholesterol and lipid accumulation. Disease‐causing missense and folding‐defective mutations result in protein mislocalization and enhanced degradation through quality control pathways, thereby impairing cholesterol export. Genetic studies have even linked specific NPC1 alleles to metabolic traits such as obesity, underscoring its broader role in organismal lipid homeostasis. Recent therapeutic approaches have focused on pharmacological chaperones and strategies to stabilize misfolded NPC1, thereby restoring proper cholesterol trafficking and ameliorating disease phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marceline Côté, John Misasi, Tao Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10380"}], "href": "https://doi.org/10.1038/nature10380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21866101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21866101"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jan E Carette, Matthijs Raaben, Anthony C Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10348"}], "href": "https://doi.org/10.1038/nature10348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21866103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21866103"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Emily Happy Miller, Gregor Obernosterer, Matthijs Raaben, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ebola virus entry requires the host-programmed recognition of an intracellular receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2012.53"}], "href": "https://doi.org/10.1038/emboj.2012.53"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22395071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22395071"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Han Wang, Yi Shi, Jian Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2015.12.044"}], "href": "https://doi.org/10.1016/j.cell.2015.12.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26771495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26771495"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Andrey Frolov, Sarah E Zielinski, Jan R Crowley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M302588200"}], "href": "https://doi.org/10.1074/jbc.M302588200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12719428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12719428"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nobutaka Ohgami, Dennis C Ko, Matthew Thomas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0405255101"}], "href": "https://doi.org/10.1073/pnas.0405255101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15314240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15314240"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rodney E Infante, Arun Radhakrishnan, Lina Abi-Mosleh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Purified NPC1 protein: II. Localization of sterol binding to a 240-amino acid soluble luminal loop."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M707944200"}], "href": "https://doi.org/10.1074/jbc.M707944200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17989072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17989072"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ronghua Liu, Peihua Lu, Joseph W K Chu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of fluorescent sterol binding to purified human NPC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M803741200"}], "href": "https://doi.org/10.1074/jbc.M803741200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19029290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19029290"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hyock Joo Kwon, Lina Abi-Mosleh, Michael L Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ebolavirus Glycoprotein Directs Fusion through NPC1+ Endolysosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01828-15"}], "href": "https://doi.org/10.1128/JVI.01828-15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26468524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26468524"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaochun Li, Jiawei Wang, Elias Coutavas, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "NPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-12152-2"}], "href": "https://doi.org/10.1038/s41467-019-12152-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31537798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31537798"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hongwu Qian, Xuelan Wu, Ximing Du, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "NPC1: Complete genomic sequence, mutation analysis, and characterization of haplotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.10016"}], "href": "https://doi.org/10.1002/humu.10016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11754101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11754101"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Mark E Gelsthorpe, Nikola Baumann, Elizabeth Millard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Niemann-Pick type C1 I1061T mutant encodes a functional protein that is selected for endoplasmic reticulum-associated degradation due to protein misfolding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M708735200"}], "href": "https://doi.org/10.1074/jbc.M708735200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18216017"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18216017"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "David Meyre, Jérôme Delplanque, Jean-Claude Chèvre, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Reduction of TMEM97 increases NPC1 protein levels and restores cholesterol trafficking in Niemann-pick type C1 disease cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw204"}], "href": "https://doi.org/10.1093/hmg/ddw204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27378690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27378690"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Xiaochun Li, Feiran Lu, Michael N Trinh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "3.3 Å structure of Niemann-Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1711716114"}], "href": "https://doi.org/10.1073/pnas.1711716114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28784760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28784760"}]}]}]}
Synonyms	SLC65A1, NPC, POGZ
Proteins	NPC1_HUMAN
NCBI Gene ID	4864
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NPC1 has 15,070 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 133 datasets.

Click the + buttons to view associations for NPC1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NPC1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by NPC1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NPC1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of NPC1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of NPC1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NPC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NPC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NPC1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of NPC1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NPC1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NPC1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of NPC1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NPC1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NPC1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NPC1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NPC1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NPC1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NPC1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NPC1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with NPC1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with NPC1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of NPC1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing NPC1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NPC1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NPC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NPC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NPC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NPC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NPC1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NPC1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NPC1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NPC1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with NPC1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NPC1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NPC1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for NPC1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving NPC1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving NPC1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with NPC1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NPC1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NPC1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.