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Protein

NPC intracellular cholesterol transporter 1

Gene

NPC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:9211849, PubMed:9927649, PubMed:10821832, PubMed:18772377, PubMed:27238017, PubMed:12554680). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1 (PubMed:9211849, PubMed:9927649, PubMed:18772377, PubMed:19563754, PubMed:27238017, PubMed:28784760). Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket (PubMed:19563754). Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals (Probable).Curated8 Publications
(Microbial infection) Acts as an endosomal entry receptor for ebolavirus.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei41CholesterolCombined sources1 Publication1 Publication1
Binding sitei79CholesterolCombined sources1 Publication1 Publication1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei108Important for cholesterol binding1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

  • cholesterol binding Source: UniProtKB
  • signaling receptor activity Source: ProtInc
  • sterol transporter activity Source: ProtInc
  • transmembrane signaling receptor activity Source: ProtInc
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processCholesterol metabolism, Host-virus interaction, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-8964038 LDL clearance

Protein family/group databases

Transport Classification Database

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TCDBi
2.A.6.6.1 the resistance-nodulation-cell division (rnd) superfamily

Chemistry databases

SwissLipids knowledge resource for lipid biology

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SwissLipidsi
SLP:000000478

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
NPC intracellular cholesterol transporter 1Imported
Alternative name(s):
Niemann-Pick C1 protein1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:NPC1Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 18

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000141458.12

Human Gene Nomenclature Database

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HGNCi
HGNC:7897 NPC1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
607623 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O15118

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini23 – 261Lumenal1 PublicationAdd BLAST239
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei262 – 282Helical1 PublicationAdd BLAST21
Topological domaini283 – 350Cytoplasmic1 PublicationAdd BLAST68
Transmembranei351 – 371Helical2 PublicationsAdd BLAST21
Topological domaini372 – 620Lumenal2 PublicationsAdd BLAST249
Transmembranei621 – 641Helical2 PublicationsAdd BLAST21
Topological domaini642 – 653Cytoplasmic1 PublicationAdd BLAST12
Transmembranei654 – 675Helical1 PublicationAdd BLAST22
Topological domaini676 – 685Lumenal1 Publication10
Transmembranei686 – 706Helical1 PublicationAdd BLAST21
Topological domaini707 – 730Cytoplasmic1 PublicationAdd BLAST24
Transmembranei731 – 751Helical1 PublicationAdd BLAST21
Topological domaini752 – 759Lumenal1 Publication8
Transmembranei760 – 783Helical1 PublicationAdd BLAST24
Topological domaini784 – 832Cytoplasmic1 PublicationAdd BLAST49
Transmembranei833 – 853Helical1 PublicationAdd BLAST21
Topological domaini854 – 1097Lumenal1 PublicationAdd BLAST244
Transmembranei1098 – 1118Helical1 PublicationAdd BLAST21
Topological domaini1119 – 1124Cytoplasmic1 Publication6
Transmembranei1125 – 1145Helical1 PublicationAdd BLAST21
Topological domaini1146 – 1150Lumenal1 Publication5
Transmembranei1151 – 1171Helical1 PublicationAdd BLAST21
Topological domaini1172 – 1194Cytoplasmic1 PublicationAdd BLAST23
Transmembranei1195 – 1215Helical1 PublicationAdd BLAST21
Topological domaini1216 – 1223Lumenal1 Publication8
Transmembranei1224 – 1244Helical1 PublicationAdd BLAST21
Topological domaini1245 – 1278Cytoplasmic1 PublicationAdd BLAST34

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Niemann-Pick disease C1 (NPC1)20 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C1 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood. An allelic variant of Niemann-Pick disease type C1 is found in people with Nova Scotia ancestry. Patients with the Nova Scotian clinical variant are less severely affected.
See also OMIM:257220
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_04317263C → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs747049347Ensembl.1
Natural variantiVAR_04317374C → Y in NPC1. 1 Publication1
Natural variantiVAR_04317492Q → R in NPC1. 2 Publications1
Natural variantiVAR_043175113C → R in NPC1; partially mislocalized from late endocytic organelles diffusely to the cell periphery; localizes to the endoplasmic reticulum Rab7-negative endosomes and the cell surface; does not clears the lysosomal cholesterol accumulation in NPC1-deficient cells. 1 PublicationCorresponds to variant dbSNP:rs120074136EnsemblClinVar.1
Natural variantiVAR_043176137T → M in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs372947142EnsemblClinVar.1
Natural variantiVAR_043178166P → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs866966704Ensembl.1
Natural variantiVAR_008815177C → G in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_015561177C → Y in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs80358252EnsemblClinVar.1
Natural variantiVAR_043179222N → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs55680026EnsemblClinVar.1
Natural variantiVAR_043180231V → G in NPC1. 1 Publication1
Natural variantiVAR_043181242D → H in NPC1. 1 Publication1
Natural variantiVAR_043182242D → N in NPC1. 1 Publication1
Natural variantiVAR_043183247C → Y in NPC1. 1 Publication1
Natural variantiVAR_043184248G → V in NPC1. 1 Publication1
Natural variantiVAR_043185272M → R in NPC1. 1 Publication1
Natural variantiVAR_043187372R → W in NPC1. 1 Publication1
Natural variantiVAR_015562378V → A in NPC1. 1 PublicationCorresponds to variant dbSNP:rs120074134EnsemblClinVar.1
Natural variantiVAR_043188380L → F in NPC1. 1 Publication1
Natural variantiVAR_043190388A → P in NPC1. 1 Publication1
Natural variantiVAR_043191389R → C in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1053321823Ensembl.1
Natural variantiVAR_043192401P → T in NPC1. 1 Publication1
Natural variantiVAR_043193404R → P in NPC1. 1 Publication1
Natural variantiVAR_043194404R → Q in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs139751448EnsemblClinVar.1
Natural variantiVAR_043195404R → W in NPC1. 1 Publication1
Natural variantiVAR_043196433P → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1064793791Ensembl.1
Natural variantiVAR_043197434P → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs774333145EnsemblClinVar.1
Natural variantiVAR_043199451E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs781065429EnsemblClinVar.1
Natural variantiVAR_008820473S → P in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043200474P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs372445155EnsemblClinVar.1
Natural variantiVAR_043201479C → Y in NPC1. 1 Publication1
Natural variantiVAR_043202509Y → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1190383931Ensembl.1
Natural variantiVAR_008821510H → P in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043204512H → R in NPC1. 1 Publication1
Natural variantiVAR_008822518R → Q in NPC1; late infantile form; Common in Japanese. 2 PublicationsCorresponds to variant dbSNP:rs483352886EnsemblClinVar.1
Natural variantiVAR_043205518R → W in NPC1; decreased affinity for NPC2; decreased cholesterol transfer from NPC2 to NPC1. 2 PublicationsCorresponds to variant dbSNP:rs377515417EnsemblClinVar.1
Natural variantiVAR_043206521A → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs138184115EnsemblClinVar.1
Natural variantiVAR_043207537F → L in NPC1. 1 Publication1
Natural variantiVAR_043208543P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs369368181EnsemblClinVar.1
Natural variantiVAR_043209574T → K in NPC1. 1
Natural variantiVAR_043210576K → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761660695Ensembl.1
Natural variantiVAR_043211605A → V in NPC1. 1 Publication1
Natural variantiVAR_043212612E → D in NPC1. 1 Publication1
Natural variantiVAR_043213615R → C in NPC1. 1 PublicationCorresponds to variant dbSNP:rs745777805EnsemblClinVar.1
Natural variantiVAR_043214615R → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs773351341Ensembl.1
Natural variantiVAR_043215631M → R in NPC1. 2 Publications1
Natural variantiVAR_043216640G → R in NPC1. 1 Publication1
Natural variantiVAR_043217652S → W in NPC1. 1 PublicationCorresponds to variant dbSNP:rs765652543Ensembl.1
Natural variantiVAR_043218660G → S in NPC1. 1 Publication1
Natural variantiVAR_043219664V → M in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs376213990EnsemblClinVar.1
Natural variantiVAR_043220666S → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs750480579Ensembl.1
Natural variantiVAR_043221670C → W in NPC1. 1 Publication1
Natural variantiVAR_043222673G → V in NPC1. 1 Publication1
Natural variantiVAR_043223684L → F in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1057518942Ensembl.1
Natural variantiVAR_043224691P → L in NPC1. 1 Publication1
Natural variantiVAR_043225695L → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs370323921Ensembl.1
Natural variantiVAR_043226700D → N in NPC1. 1 Publication1
Natural variantiVAR_043227703F → S in NPC1. 1 Publication1
Natural variantiVAR_043228724L → P in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1393388896Ensembl.1
Natural variantiVAR_043229727V → F in NPC1. 1 Publication1
Natural variantiVAR_043230734S → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs757475924EnsemblClinVar.1
Natural variantiVAR_043231742E → K in NPC1. 1 Publication1
Natural variantiVAR_043232745A → E in NPC1. 1 PublicationCorresponds to variant dbSNP:rs752386083EnsemblClinVar.1
Natural variantiVAR_043233754M → K in NPC1. 1 Publication1
Natural variantiVAR_043234763F → L in NPC1. 1 Publication1
Natural variantiVAR_043235767A → V in NPC1. 1 Publication1
Natural variantiVAR_043236775Q → P in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs80358253EnsemblClinVar.1
Natural variantiVAR_043237789R → C in NPC1. 1 Publication1
Natural variantiVAR_043238789R → G in NPC1. 1 Publication1
Natural variantiVAR_043239825Y → C in NPC1. 4 PublicationsCorresponds to variant dbSNP:rs550562774EnsemblClinVar.1
Natural variantiVAR_043240849S → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1057519242Ensembl.1
Natural variantiVAR_043241862Q → L in NPC1. 1 Publication1
Natural variantiVAR_043242865S → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs1160114136Ensembl.1
Natural variantiVAR_043243871Y → C in NPC1. 1 Publication1
Natural variantiVAR_043245874D → V in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs372030650EnsemblClinVar.1
Natural variantiVAR_043246888P → S in NPC1. 1 Publication1
Natural variantiVAR_008826889V → M in NPC1; adult form. 1 PublicationCorresponds to variant dbSNP:rs120074130EnsemblClinVar.1
Natural variantiVAR_043247890Y → C in NPC1. 1 Publication1
Natural variantiVAR_043248899Y → D in NPC1. 1 Publication1
Natural variantiVAR_043249910G → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs768999208EnsemblClinVar.1
Natural variantiVAR_043250917D → Y in NPC1. 1 Publication1
Natural variantiVAR_043251926A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs564631426Ensembl.1
Natural variantiVAR_043252927A → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753768576EnsemblClinVar.1
Natural variantiVAR_008827928Q → P in NPC1. Corresponds to variant dbSNP:rs28940897EnsemblClinVar.1
Natural variantiVAR_043253929L → P in NPC1. 1 Publication1
Natural variantiVAR_008828934R → Q in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs786204714EnsemblClinVar.1
Natural variantiVAR_008829940S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs143124972EnsemblClinVar.1
Natural variantiVAR_043254942W → C in NPC1. 2 Publications1
Natural variantiVAR_043255943I → M in NPC1. 1 Publication1
Natural variantiVAR_043256944D → N in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs748837410Ensembl.1
Natural variantiVAR_043257945D → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1428599096Ensembl.1
Natural variantiVAR_043258948D → H in NPC1. 1 Publication1
Natural variantiVAR_008830948D → N in NPC1. 3 Publications1
Natural variantiVAR_043259948D → Y in NPC1. 1 Publication1
Natural variantiVAR_015563950V → M in NPC1; adult form. 2 PublicationsCorresponds to variant dbSNP:rs120074135EnsemblClinVar.1
Natural variantiVAR_008831954S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs543206298EnsemblClinVar.1
Natural variantiVAR_008832956C → Y in NPC1; late infantile form. 1 Publication1
Natural variantiVAR_043260958R → L in NPC1. 1 Publication1
Natural variantiVAR_015564958R → Q in NPC1. 1 PublicationCorresponds to variant dbSNP:rs120074132EnsemblClinVar.1
Natural variantiVAR_043261959V → E in NPC1. 1 Publication1
Natural variantiVAR_043262961 – 966NITDQF → S in NPC1. 1 Publication6
Natural variantiVAR_043263961N → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs34084984EnsemblClinVar.1
Natural variantiVAR_043264968N → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs773767253EnsemblClinVar.1
Natural variantiVAR_043266976C → R in NPC1. 1 Publication1
Natural variantiVAR_015565978R → C in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs28942108EnsemblClinVar.1
Natural variantiVAR_043267986G → S in NPC1. 1 Publication1
Natural variantiVAR_043268992G → A in NPC1. 1 PublicationCorresponds to variant dbSNP:rs757534240Ensembl.1
Natural variantiVAR_015566992G → R in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs80358254EnsemblClinVar.1
Natural variantiVAR_008833992G → W in NPC1; found in the Nova Scotian clinical variant. 5 PublicationsCorresponds to variant dbSNP:rs80358254EnsemblClinVar.1
Natural variantiVAR_043269996M → R in NPC1. 1 Publication1
Natural variantiVAR_0432701004S → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs150334966EnsemblClinVar.1
Natural variantiVAR_0088341007P → A in NPC1. 7 PublicationsCorresponds to variant dbSNP:rs80358257EnsemblClinVar.1
Natural variantiVAR_0432711012G → D in NPC1. 1 Publication1
Natural variantiVAR_0432721015G → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761773567Ensembl.1
Natural variantiVAR_0432731016H → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs140211089Ensembl.1
Natural variantiVAR_0432741023V → G in NPC1. 1 Publication1
Natural variantiVAR_0432751034G → R in NPC1. 1 Publication1
Natural variantiVAR_0155671035A → V in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs28942107EnsemblClinVar.1
Natural variantiVAR_0432761036T → K in NPC1. 1 Publication1
Natural variantiVAR_0088351036T → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942104EnsemblClinVar.1
Natural variantiVAR_0432781054A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs80358258EnsemblClinVar.1
Natural variantiVAR_0432791059R → Q in NPC1. 1 PublicationCorresponds to variant dbSNP:rs771000314Ensembl.1
Natural variantiVAR_0088361061I → T in NPC1; late infantile form. 10 PublicationsCorresponds to variant dbSNP:rs80358259EnsemblClinVar.1
Natural variantiVAR_0432801062A → V in NPC1. 1 Publication1
Natural variantiVAR_0432811066T → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs772622214Ensembl.1
Natural variantiVAR_0432821087F → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs746715353EnsemblClinVar.1
Natural variantiVAR_0088371088Y → C in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs28942106EnsemblClinVar.1
Natural variantiVAR_0432831089E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs374526072EnsemblClinVar.1
Natural variantiVAR_0432841094I → T in NPC1. 1 Publication1
Natural variantiVAR_0432851097D → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758829443Ensembl.1
Natural variantiVAR_0432861137N → I in NPC1. 1 Publication1
Natural variantiVAR_0432871140G → V in NPC1. 1 Publication1
Natural variantiVAR_0432881142M → T in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs778878523EnsemblClinVar.1
Natural variantiVAR_0432891150N → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs34715591EnsemblClinVar.1
Natural variantiVAR_0432901156N → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942105EnsemblClinVar.1
Natural variantiVAR_0088381156N → S in NPC1. 4 PublicationsCorresponds to variant dbSNP:rs28942105EnsemblClinVar.1
Natural variantiVAR_0432911165V → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs748862167EnsemblClinVar.1
Natural variantiVAR_0088391167F → L in NPC1. 1
Natural variantiVAR_0432921168C → Y in NPC1. 1 Publication1
Natural variantiVAR_0432931174A → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs780175800Ensembl.1
Natural variantiVAR_0088401186R → H in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs200444084EnsemblClinVar.1
Natural variantiVAR_0432941189E → G in NPC1. 1 PublicationCorresponds to variant dbSNP:rs369098773EnsemblClinVar.1
Natural variantiVAR_0432951205T → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758902805EnsemblClinVar.1
Natural variantiVAR_0432961205T → R in NPC1. 1 Publication1
Natural variantiVAR_0432971212V → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753419933EnsemblClinVar.1
Natural variantiVAR_0088411213L → F in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs120074131EnsemblClinVar.1
Natural variantiVAR_0088421213L → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs766178353Ensembl.1
Natural variantiVAR_0432981216A → V in NPC1. 1 Publication1
Natural variantiVAR_0432991224F → L in NPC1. 1 Publication1
Natural variantiVAR_0433001236G → E in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761653115Ensembl.1
Natural variantiVAR_0433011240G → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs745892286Ensembl.1
Natural variantiVAR_0433021249S → G in NPC1. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi25 – 257Missing : Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1. 1 PublicationAdd BLAST233
Mutagenesisi26 – 27VW → AA: Nearly abolishes 25-hydroxycholesterol binding. Reduces cholesterol binding. 1 Publication2
Mutagenesisi39 – 41RYN → AAA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication3
Mutagenesisi41N → A: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication1
Mutagenesisi63C → S: Loss of function. 1 Publication1
Mutagenesisi70N → Q: Reduces glycosylation; when associated with Q-122 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication1
Mutagenesisi74 – 75CC → SS: Loss of function. 1 Publication2
Mutagenesisi82 – 83TL → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication2
Mutagenesisi88Q → A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-92 and A-96. 1 Publication1
Mutagenesisi92Q → A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-96. 1 Publication1
Mutagenesisi96R → A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-92. 1 Publication1
Mutagenesisi97C → S: Loss of function. 1 Publication1
Mutagenesisi101 – 102FY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi106 – 108NLF → AAA: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication3
Mutagenesisi110 – 112ELT → AAA: No effect on cholesterol and 25-hydroxycholesterol binding and transfer. 1 Publication3
Mutagenesisi122N → Q: Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication1
Mutagenesisi144 – 145LQ → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi146 – 147YY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi175 – 176LL → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Decreases affinity for NPC2. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 2 Publications2
Mutagenesisi180 – 182DAD → AAA: Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication3
Mutagenesisi185N → Q: Reduces glycosylation; when associated with Q-70 and Q-122. No effect on cholesterol and 25-hydroxycholesterol binding. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication1
Mutagenesisi187 – 188TN → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication2
Mutagenesisi191 – 192EY → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Nearly abolishes cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication2
Mutagenesisi195 – 196NK → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication2
Mutagenesisi197 – 198DN → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication2
Mutagenesisi199 – 200GQ → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication2
Mutagenesisi202 – 203PF → AA: Abolishes cholesterol and 25-hydroxycholesterol binding. Abolishes cholesterol transfer from NPC2 to NPC1. 2 Publications2
Mutagenesisi204 – 205TI → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication2
Mutagenesisi230 – 234Missing : Decreased cholesterol transport. 1 Publication5
Mutagenesisi249 – 257Missing : Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1. 1 Publication9
Mutagenesisi423 – 424YP → GG: Strongly reduces interaction with ebolavirus glycoprotein. 1 Publication2
Mutagenesisi503F → A or G: Loss of interaction with ebolavirus glycoprotein. 1 Publication1
Mutagenesisi504F → A or G: Loss of interaction with ebolavirus glycoprotein. 1 Publication1
Mutagenesisi506Y → A: Loss of interaction with ebolavirus glycoprotein. 1 Publication1
Mutagenesisi660G → R: Loss of function. 1 Publication1
Mutagenesisi691P → S: Abolishes cholesterol transport. No effect on subcellular location. 1 Publication1
Mutagenesisi909 – 917CGGMGCNND → A: Abolishes cholesterol transport. No effect on subcellular location. 1 Publication9
Mutagenesisi1275 – 1278Missing : Loss of location in lysosomes. 1 Publication4

Keywords - Diseasei

Disease mutation, Niemann-Pick disease

Organism-specific databases

DisGeNET

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DisGeNETi
4864

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
NPC1

MalaCards human disease database

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MalaCardsi
NPC1
MIMi257220 phenotype

Open Targets

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OpenTargetsi
ENSG00000141458

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
216986 Niemann-Pick disease type C, adult neurologic onset
216981 Niemann-Pick disease type C, juvenile neurologic onset
216978 Niemann-Pick disease type C, late infantile neurologic onset
216975 Niemann-Pick disease type C, severe early infantile neurologic onset
216972 Niemann-Pick disease type C, severe perinatal form

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA31698

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1293277

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
NPC1

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 22Sequence analysisAdd BLAST22
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000002326123 – 1278NPC intracellular cholesterol transporter 1Add BLAST1256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi25 ↔ 74Combined sources2 Publications
Disulfide bondi31 ↔ 42Combined sources2 Publications