Protein

NPC intracellular cholesterol transporter 1

Gene

NPC1

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

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 key	Position(s)	DescriptionActions	Length
Binding siteⁱ	41	CholesterolCombined sources1 Publication1 Publication	1
Binding siteⁱ	79	CholesterolCombined sources1 Publication1 Publication	1
Siteⁱ	108	Important for cholesterol binding1 Publication	1

GO - Molecular functionⁱ

cholesterol binding
Source: UniProtKB
Inferred from direct assayⁱ
- 18772377
signaling receptor activity
Source: ProtInc
Traceable author statementⁱ
- 9211849
sterol transporter activity
Source: ProtInc
Traceable author statementⁱ
- 9927649
transmembrane signaling receptor activity
Source: ProtInc
Traceable author statementⁱ
- 10521290
virus receptor activity Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

adult walking behavior Source: Ensembl
autophagy
Source: MGI
Inferred from genetic interactionⁱ
- 19074461
bile acid metabolic process Source: UniProtKB
cellular response to low-density lipoprotein particle stimulus Source: Ensembl
cellular response to steroid hormone stimulus Source: Ensembl
cholesterol efflux
Source: BHF-UCL
Inferred from direct assayⁱ
- 16141411
cholesterol homeostasis
Source: UniProtKB
Inferred from direct assayⁱ
- 12719428
cholesterol metabolic process Source: UniProtKB-KW
cholesterol transport
Source: UniProtKB
Inferred from direct assayⁱ
- 18772377
endocytosis Source: Ensembl
establishment of protein localization to membrane
Source: UniProtKB
Inferred from direct assayⁱ
- 23360953
intracellular cholesterol transport
Source: UniProtKB
Inferred from mutant phenotypeⁱ
low-density lipoprotein particle clearance Source: Reactome
lysosomal transport Source: UniProtKB
membrane raft organization
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23360953
negative regulation of cell death Source: Ensembl
negative regulation of macroautophagy Source: Ensembl
protein glycosylation
Source: UniProtKB
Inferred from direct assayⁱ
- 10821832
response to cadmium ion Source: Ensembl
response to drug Source: Ensembl
viral entry into host cell
Source: CACAO
Inferred from mutant phenotypeⁱ
- 21866101
- 21866103

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Host cell receptor for virus entry, Receptor
Biological process	Cholesterol metabolism, Host-virus interaction, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

Reactomeⁱ	R-HSA-8964038 LDL clearance

Reactomeⁱ

R-HSA-8964038 LDL clearance

Protein family/group databases

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

TCDBⁱ

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

Chemistry databases

SwissLipidsⁱ	SLP:000000478

SwissLipidsⁱ

SLP:000000478

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: NPC intracellular cholesterol transporter 1Imported Alternative name(s): Niemann-Pick C1 protein1 Publication
Gene namesⁱ	Name:NPC1Imported
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 18

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000141458.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:7897 NPC1
MIMⁱ	607623 gene
neXtProtⁱ	NX_O15118

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	23 – 261	Lumenal1 PublicationAdd BLAST	239
Transmembraneⁱ	262 – 282	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	283 – 350	Cytoplasmic1 PublicationAdd BLAST	68
Transmembraneⁱ	351 – 371	Helical2 PublicationsAdd BLAST	21
Topological domainⁱ	372 – 620	Lumenal2 PublicationsAdd BLAST	249
Transmembraneⁱ	621 – 641	Helical2 PublicationsAdd BLAST	21
Topological domainⁱ	642 – 653	Cytoplasmic1 PublicationAdd BLAST	12
Transmembraneⁱ	654 – 675	Helical1 PublicationAdd BLAST	22
Topological domainⁱ	676 – 685	Lumenal1 Publication	10
Transmembraneⁱ	686 – 706	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	707 – 730	Cytoplasmic1 PublicationAdd BLAST	24
Transmembraneⁱ	731 – 751	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	752 – 759	Lumenal1 Publication	8
Transmembraneⁱ	760 – 783	Helical1 PublicationAdd BLAST	24
Topological domainⁱ	784 – 832	Cytoplasmic1 PublicationAdd BLAST	49
Transmembraneⁱ	833 – 853	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	854 – 1097	Lumenal1 PublicationAdd BLAST	244
Transmembraneⁱ	1098 – 1118	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	1119 – 1124	Cytoplasmic1 Publication	6
Transmembraneⁱ	1125 – 1145	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	1146 – 1150	Lumenal1 Publication	5
Transmembraneⁱ	1151 – 1171	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	1172 – 1194	Cytoplasmic1 PublicationAdd BLAST	23
Transmembraneⁱ	1195 – 1215	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	1216 – 1223	Lumenal1 Publication	8
Transmembraneⁱ	1224 – 1244	Helical1 PublicationAdd BLAST	21
Topological domainⁱ	1245 – 1278	Cytoplasmic1 PublicationAdd BLAST	34

Keywords - Cellular componentⁱ

Endosome, Lysosome, Membrane

Pathology & Biotechⁱ

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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_043172	63	C → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs747049347Ensembl.	1
Natural variantⁱVAR_043173	74	C → Y in NPC1. 1 Publication	1
Natural variantⁱVAR_043174	92	Q → R in NPC1. 2 Publications	1
Natural variantⁱVAR_043175	113	C → 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_043176	137	T → M in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs372947142EnsemblClinVar.	1
Natural variantⁱVAR_043178	166	P → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs866966704Ensembl.	1
Natural variantⁱVAR_008815	177	C → G in NPC1; late infantile form. 1 Publication	1
Natural variantⁱVAR_015561	177	C → Y in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs80358252EnsemblClinVar.	1
Natural variantⁱVAR_043179	222	N → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs55680026EnsemblClinVar.	1
Natural variantⁱVAR_043180	231	V → G in NPC1. 1 Publication	1
Natural variantⁱVAR_043181	242	D → H in NPC1. 1 Publication	1
Natural variantⁱVAR_043182	242	D → N in NPC1. 1 Publication	1
Natural variantⁱVAR_043183	247	C → Y in NPC1. 1 Publication	1
Natural variantⁱVAR_043184	248	G → V in NPC1. 1 Publication	1
Natural variantⁱVAR_043185	272	M → R in NPC1. 1 Publication	1
Natural variantⁱVAR_043187	372	R → W in NPC1. 1 Publication	1
Natural variantⁱVAR_015562	378	V → A in NPC1. 1 PublicationCorresponds to variant dbSNP:rs120074134EnsemblClinVar.	1
Natural variantⁱVAR_043188	380	L → F in NPC1. 1 Publication	1
Natural variantⁱVAR_043190	388	A → P in NPC1. 1 Publication	1
Natural variantⁱVAR_043191	389	R → C in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1053321823Ensembl.	1
Natural variantⁱVAR_043192	401	P → T in NPC1. 1 Publication	1
Natural variantⁱVAR_043193	404	R → P in NPC1. 1 Publication	1
Natural variantⁱVAR_043194	404	R → Q in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs139751448EnsemblClinVar.	1
Natural variantⁱVAR_043195	404	R → W in NPC1. 1 Publication	1
Natural variantⁱVAR_043196	433	P → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1064793791Ensembl.	1
Natural variantⁱVAR_043197	434	P → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs774333145EnsemblClinVar.	1
Natural variantⁱVAR_043199	451	E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs781065429EnsemblClinVar.	1
Natural variantⁱVAR_008820	473	S → P in NPC1; late infantile form. 1 Publication	1
Natural variantⁱVAR_043200	474	P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs372445155EnsemblClinVar.	1
Natural variantⁱVAR_043201	479	C → Y in NPC1. 1 Publication	1
Natural variantⁱVAR_043202	509	Y → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1190383931Ensembl.	1
Natural variantⁱVAR_008821	510	H → P in NPC1; late infantile form. 1 Publication	1
Natural variantⁱVAR_043204	512	H → R in NPC1. 1 Publication	1
Natural variantⁱVAR_008822	518	R → Q in NPC1; late infantile form; Common in Japanese. 2 PublicationsCorresponds to variant dbSNP:rs483352886EnsemblClinVar.	1
Natural variantⁱVAR_043205	518	R → W in NPC1; decreased affinity for NPC2; decreased cholesterol transfer from NPC2 to NPC1. 2 PublicationsCorresponds to variant dbSNP:rs377515417EnsemblClinVar.	1
Natural variantⁱVAR_043206	521	A → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs138184115EnsemblClinVar.	1
Natural variantⁱVAR_043207	537	F → L in NPC1. 1 Publication	1
Natural variantⁱVAR_043208	543	P → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs369368181EnsemblClinVar.	1
Natural variantⁱVAR_043209	574	T → K in NPC1.	1
Natural variantⁱVAR_043210	576	K → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761660695Ensembl.	1
Natural variantⁱVAR_043211	605	A → V in NPC1. 1 Publication	1
Natural variantⁱVAR_043212	612	E → D in NPC1. 1 Publication	1
Natural variantⁱVAR_043213	615	R → C in NPC1. 1 PublicationCorresponds to variant dbSNP:rs745777805Ensembl.	1
Natural variantⁱVAR_043214	615	R → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs773351341Ensembl.	1
Natural variantⁱVAR_043215	631	M → R in NPC1. 2 Publications	1
Natural variantⁱVAR_043216	640	G → R in NPC1. 1 Publication	1
Natural variantⁱVAR_043217	652	S → W in NPC1. 1 PublicationCorresponds to variant dbSNP:rs765652543Ensembl.	1
Natural variantⁱVAR_043218	660	G → S in NPC1. 1 Publication	1
Natural variantⁱVAR_043219	664	V → M in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs376213990EnsemblClinVar.	1
Natural variantⁱVAR_043220	666	S → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs750480579Ensembl.	1
Natural variantⁱVAR_043221	670	C → W in NPC1. 1 Publication	1
Natural variantⁱVAR_043222	673	G → V in NPC1. 1 Publication	1
Natural variantⁱVAR_043223	684	L → F in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1057518942Ensembl.	1
Natural variantⁱVAR_043224	691	P → L in NPC1. 1 Publication	1
Natural variantⁱVAR_043225	695	L → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs370323921Ensembl.	1
Natural variantⁱVAR_043226	700	D → N in NPC1. 1 Publication	1
Natural variantⁱVAR_043227	703	F → S in NPC1. 1 Publication	1
Natural variantⁱVAR_043228	724	L → P in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1393388896Ensembl.	1
Natural variantⁱVAR_043229	727	V → F in NPC1. 1 Publication	1
Natural variantⁱVAR_043230	734	S → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs757475924EnsemblClinVar.	1
Natural variantⁱVAR_043231	742	E → K in NPC1. 1 Publication	1
Natural variantⁱVAR_043232	745	A → E in NPC1. 1 PublicationCorresponds to variant dbSNP:rs752386083EnsemblClinVar.	1
Natural variantⁱVAR_043233	754	M → K in NPC1. 1 Publication	1
Natural variantⁱVAR_043234	763	F → L in NPC1. 1 Publication	1
Natural variantⁱVAR_043235	767	A → V in NPC1. 1 Publication	1
Natural variantⁱVAR_043236	775	Q → P in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs80358253EnsemblClinVar.	1
Natural variantⁱVAR_043237	789	R → C in NPC1. 1 Publication	1
Natural variantⁱVAR_043238	789	R → G in NPC1. 1 Publication	1
Natural variantⁱVAR_043239	825	Y → C in NPC1. 4 PublicationsCorresponds to variant dbSNP:rs550562774EnsemblClinVar.	1
Natural variantⁱVAR_043240	849	S → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1057519242Ensembl.	1
Natural variantⁱVAR_043241	862	Q → L in NPC1. 1 Publication	1
Natural variantⁱVAR_043242	865	S → L in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs1160114136Ensembl.	1
Natural variantⁱVAR_043243	871	Y → C in NPC1. 1 Publication	1
Natural variantⁱVAR_043245	874	D → V in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs372030650EnsemblClinVar.	1
Natural variantⁱVAR_043246	888	P → S in NPC1. 1 Publication	1
Natural variantⁱVAR_008826	889	V → M in NPC1; adult form. 1 PublicationCorresponds to variant dbSNP:rs120074130EnsemblClinVar.	1
Natural variantⁱVAR_043247	890	Y → C in NPC1. 1 Publication	1
Natural variantⁱVAR_043248	899	Y → D in NPC1. 1 Publication	1
Natural variantⁱVAR_043249	910	G → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs768999208EnsemblClinVar.	1
Natural variantⁱVAR_043250	917	D → Y in NPC1. 1 Publication	1
Natural variantⁱVAR_043251	926	A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs564631426Ensembl.	1
Natural variantⁱVAR_043252	927	A → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753768576EnsemblClinVar.	1
Natural variantⁱVAR_008827	928	Q → P in NPC1. Corresponds to variant dbSNP:rs28940897EnsemblClinVar.	1
Natural variantⁱVAR_043253	929	L → P in NPC1. 1 Publication	1
Natural variantⁱVAR_008828	934	R → Q in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs786204714EnsemblClinVar.	1
Natural variantⁱVAR_008829	940	S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs143124972EnsemblClinVar.	1
Natural variantⁱVAR_043254	942	W → C in NPC1. 2 Publications	1
Natural variantⁱVAR_043255	943	I → M in NPC1. 1 Publication	1
Natural variantⁱVAR_043256	944	D → N in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs748837410Ensembl.	1
Natural variantⁱVAR_043257	945	D → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs1428599096Ensembl.	1
Natural variantⁱVAR_043258	948	D → H in NPC1. 1 Publication	1
Natural variantⁱVAR_008830	948	D → N in NPC1. 3 Publications	1
Natural variantⁱVAR_043259	948	D → Y in NPC1. 1 Publication	1
Natural variantⁱVAR_015563	950	V → M in NPC1; adult form. 2 PublicationsCorresponds to variant dbSNP:rs120074135EnsemblClinVar.	1
Natural variantⁱVAR_008831	954	S → L in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs543206298EnsemblClinVar.	1
Natural variantⁱVAR_008832	956	C → Y in NPC1; late infantile form. 1 Publication	1
Natural variantⁱVAR_043260	958	R → L in NPC1. 1 Publication	1
Natural variantⁱVAR_015564	958	R → Q in NPC1. 1 PublicationCorresponds to variant dbSNP:rs120074132EnsemblClinVar.	1
Natural variantⁱVAR_043261	959	V → E in NPC1. 1 Publication	1
Natural variantⁱVAR_043262	961 – 966	NITDQF → S in NPC1. 1 Publication	6
Natural variantⁱVAR_043263	961	N → S in NPC1. 1 PublicationCorresponds to variant dbSNP:rs34084984EnsemblClinVar.	1
Natural variantⁱVAR_043264	968	N → S in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs773767253EnsemblClinVar.	1
Natural variantⁱVAR_043266	976	C → R in NPC1. 1 Publication	1
Natural variantⁱVAR_015565	978	R → C in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs28942108EnsemblClinVar.	1
Natural variantⁱVAR_043267	986	G → S in NPC1. 1 Publication	1
Natural variantⁱVAR_043268	992	G → A in NPC1. 1 PublicationCorresponds to variant dbSNP:rs757534240Ensembl.	1
Natural variantⁱVAR_015566	992	G → R in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs80358254EnsemblClinVar.	1
Natural variantⁱVAR_008833	992	G → W in NPC1; found in the Nova Scotian clinical variant. 5 PublicationsCorresponds to variant dbSNP:rs80358254EnsemblClinVar.	1
Natural variantⁱVAR_043269	996	M → R in NPC1. 1 Publication	1
Natural variantⁱVAR_043270	1004	S → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs150334966EnsemblClinVar.	1
Natural variantⁱVAR_008834	1007	P → A in NPC1. 7 PublicationsCorresponds to variant dbSNP:rs80358257EnsemblClinVar.	1
Natural variantⁱVAR_043271	1012	G → D in NPC1. 1 Publication	1
Natural variantⁱVAR_043272	1015	G → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761773567Ensembl.	1
Natural variantⁱVAR_043273	1016	H → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs140211089Ensembl.	1
Natural variantⁱVAR_043274	1023	V → G in NPC1. 1 Publication	1
Natural variantⁱVAR_043275	1034	G → R in NPC1. 1 Publication	1
Natural variantⁱVAR_015567	1035	A → V in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs28942107EnsemblClinVar.	1
Natural variantⁱVAR_043276	1036	T → K in NPC1. 1 Publication	1
Natural variantⁱVAR_008835	1036	T → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942104EnsemblClinVar.	1
Natural variantⁱVAR_043278	1054	A → T in NPC1. 1 PublicationCorresponds to variant dbSNP:rs80358258EnsemblClinVar.	1
Natural variantⁱVAR_043279	1059	R → Q in NPC1. 1 PublicationCorresponds to variant dbSNP:rs771000314Ensembl.	1
Natural variantⁱVAR_008836	1061	I → T in NPC1; late infantile form. 10 PublicationsCorresponds to variant dbSNP:rs80358259EnsemblClinVar.	1
Natural variantⁱVAR_043280	1062	A → V in NPC1. 1 Publication	1
Natural variantⁱVAR_043281	1066	T → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs772622214Ensembl.	1
Natural variantⁱVAR_043282	1087	F → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs746715353EnsemblClinVar.	1
Natural variantⁱVAR_008837	1088	Y → C in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs28942106EnsemblClinVar.	1
Natural variantⁱVAR_043283	1089	E → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs374526072EnsemblClinVar.	1
Natural variantⁱVAR_043284	1094	I → T in NPC1. 1 Publication	1
Natural variantⁱVAR_043285	1097	D → N in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758829443Ensembl.	1
Natural variantⁱVAR_043286	1137	N → I in NPC1. 1 Publication	1
Natural variantⁱVAR_043287	1140	G → V in NPC1. 1 Publication	1
Natural variantⁱVAR_043288	1142	M → T in NPC1. 2 PublicationsCorresponds to variant dbSNP:rs778878523EnsemblClinVar.	1
Natural variantⁱVAR_043289	1150	N → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs34715591EnsemblClinVar.	1
Natural variantⁱVAR_043290	1156	N → I in NPC1. 1 PublicationCorresponds to variant dbSNP:rs28942105EnsemblClinVar.	1
Natural variantⁱVAR_008838	1156	N → S in NPC1. 4 PublicationsCorresponds to variant dbSNP:rs28942105EnsemblClinVar.	1
Natural variantⁱVAR_043291	1165	V → M in NPC1. 1 PublicationCorresponds to variant dbSNP:rs748862167EnsemblClinVar.	1
Natural variantⁱVAR_008839	1167	F → L in NPC1.	1
Natural variantⁱVAR_043292	1168	C → Y in NPC1. 1 Publication	1
Natural variantⁱVAR_043293	1174	A → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs780175800Ensembl.	1
Natural variantⁱVAR_008840	1186	R → H in NPC1. 3 PublicationsCorresponds to variant dbSNP:rs200444084EnsemblClinVar.	1
Natural variantⁱVAR_043294	1189	E → G in NPC1. 1 PublicationCorresponds to variant dbSNP:rs369098773EnsemblClinVar.	1
Natural variantⁱVAR_043295	1205	T → K in NPC1. 1 PublicationCorresponds to variant dbSNP:rs758902805EnsemblClinVar.	1
Natural variantⁱVAR_043296	1205	T → R in NPC1. 1 Publication	1
Natural variantⁱVAR_043297	1212	V → L in NPC1. 1 PublicationCorresponds to variant dbSNP:rs753419933EnsemblClinVar.	1
Natural variantⁱVAR_008841	1213	L → F in NPC1; juvenile form. 1 PublicationCorresponds to variant dbSNP:rs120074131EnsemblClinVar.	1
Natural variantⁱVAR_008842	1213	L → V in NPC1. 1 PublicationCorresponds to variant dbSNP:rs766178353Ensembl.	1
Natural variantⁱVAR_043298	1216	A → V in NPC1. 1 Publication	1
Natural variantⁱVAR_043299	1224	F → L in NPC1. 1 Publication	1
Natural variantⁱVAR_043300	1236	G → E in NPC1. 1 PublicationCorresponds to variant dbSNP:rs761653115Ensembl.	1
Natural variantⁱVAR_043301	1240	G → R in NPC1. 1 PublicationCorresponds to variant dbSNP:rs745892286Ensembl.	1
Natural variantⁱVAR_043302	1249	S → G in NPC1. 1 Publication	1

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	25 – 257	Missing : Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1. 1 PublicationAdd BLAST	233
Mutagenesisⁱ	26 – 27	VW → AA: Nearly abolishes 25-hydroxycholesterol binding. Reduces cholesterol binding. 1 Publication	2
Mutagenesisⁱ	39 – 41	RYN → AAA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication	3
Mutagenesisⁱ	41	N → A: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication	1
Mutagenesisⁱ	63	C → S: Loss of function. 1 Publication	1
Mutagenesisⁱ	70	N → Q: Reduces glycosylation; when associated with Q-122 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication	1
Mutagenesisⁱ	74 – 75	CC → SS: Loss of function. 1 Publication	2
Mutagenesisⁱ	82 – 83	TL → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication	2
Mutagenesisⁱ	88	Q → A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-92 and A-96. 1 Publication	1
Mutagenesisⁱ	92	Q → A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-96. 1 Publication	1
Mutagenesisⁱ	96	R → A: Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-92. 1 Publication	1
Mutagenesisⁱ	97	C → S: Loss of function. 1 Publication	1
Mutagenesisⁱ	101 – 102	FY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication	2
Mutagenesisⁱ	106 – 108	NLF → AAA: Nearly abolishes cholesterol and 25-hydroxycholesterol binding. 1 Publication	3
Mutagenesisⁱ	110 – 112	ELT → AAA: No effect on cholesterol and 25-hydroxycholesterol binding and transfer. 1 Publication	3
Mutagenesisⁱ	122	N → Q: Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding. 1 Publication	1
Mutagenesisⁱ	144 – 145	LQ → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication	2
Mutagenesisⁱ	146 – 147	YY → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication	2
Mutagenesisⁱ	175 – 176	LL → 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 Publications	2
Mutagenesisⁱ	180 – 182	DAD → AAA: Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication	3
Mutagenesisⁱ	185	N → 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 Publication	1
Mutagenesisⁱ	187 – 188	TN → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication	2
Mutagenesisⁱ	191 – 192	EY → AA: No effect on cholesterol or 25-hydroxycholesterol binding. Nearly abolishes cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication	2
Mutagenesisⁱ	195 – 196	NK → AA: Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding. 1 Publication	2
Mutagenesisⁱ	197 – 198	DN → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication	2
Mutagenesisⁱ	199 – 200	GQ → AA: Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner. 1 Publication	2
Mutagenesisⁱ	202 – 203	PF → AA: Abolishes cholesterol and 25-hydroxycholesterol binding. Abolishes cholesterol transfer from NPC2 to NPC1. 2 Publications	2
Mutagenesisⁱ	204 – 205	TI → AA: Strongly reduces cholesterol and 25-hydroxycholesterol binding. 1 Publication	2
Mutagenesisⁱ	230 – 234	Missing : Decreased cholesterol transport. 1 Publication	5
Mutagenesisⁱ	249 – 257	Missing : Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1. 1 Publication	9
Mutagenesisⁱ	423 – 424	YP → GG: Strongly reduces interaction with ebolavirus glycoprotein. 1 Publication	2
Mutagenesisⁱ	503	F → A or G: Loss of interaction with ebolavirus glycoprotein. 1 Publication	1
Mutagenesisⁱ	504	F → A or G: Loss of interaction with ebolavirus glycoprotein. 1 Publication	1
Mutagenesisⁱ	506	Y → A: Loss of interaction with ebolavirus glycoprotein. 1 Publication	1
Mutagenesisⁱ	660	G → R: Loss of function. 1 Publication	1
Mutagenesisⁱ	691	P → S: Abolishes cholesterol transport. No effect on subcellular location. 1 Publication	1
Mutagenesisⁱ	909 – 917	CGGMGCNND → A: Abolishes cholesterol transport. No effect on subcellular location. 1 Publication	9
Mutagenesisⁱ	1275 – 1278	Missing : Loss of location in lysosomes. 1 Publication	4

Keywords - Diseaseⁱ

Disease mutation, Niemann-Pick disease

Organism-specific databases

DisGeNET More...DisGeNETⁱ	4864
GeneReviewsⁱ	NPC1
MalaCards human disease database More...MalaCardsⁱ	NPC1
MIMⁱ	257220 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000141458
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
PharmGKBⁱ	PA31698

Chemistry databases

ChEMBLⁱ	CHEMBL1293277

ChEMBLⁱ

CHEMBL1293277

Polymorphism and mutation databases

BioMutaⁱ	NPC1

BioMutaⁱ

NPC1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 22	Sequence analysisAdd BLAST		22
ChainⁱPRO_0000023261	23 – 1278	NPC intracellular cholesterol transporter 1Add BLAST		1256

Amino acid modifications

Feature key	Position(s)	DescriptionActions
Disulfide bondⁱ	25 ↔ 74	Combined sources2 Publications
Disulfide bondⁱ	31 ↔ 42	Combined sources2 Publications
Disulfide bondⁱ	63 ↔ 10

UniProtKB - O15118 (NPC1_HUMAN)

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NPC intracellular cholesterol transporter 1

NPC1

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Functionⁱ

Sites

GO - Molecular functionⁱ

GO - Biological processⁱ

Keywordsⁱ

Enzyme and pathway databases

Protein family/group databases

Chemistry databases

Names & Taxonomyⁱ

Organism-specific databases

Subcellular locationⁱ

Lysosome

Endosome

Endoplasmic reticulum

Endosome

Extracellular region or secreted

Golgi apparatus

Lysosome

Nucleus

Plasma Membrane

Other locations

Topology

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Niemann-Pick disease C1 (NPC1)20 Publications

Mutagenesis

Keywords - Diseaseⁱ

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

PTM / Processingⁱ

Molecule processing

Amino acid modifications

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - O15118 (NPC1_HUMAN)

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NPC intracellular cholesterol transporter 1

NPC1

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<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

Sites

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GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

Chemistry databases

<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

Organism-specific databases

<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

Lysosome

Endosome

Endoplasmic reticulum

Endosome

Extracellular region or secreted

Golgi apparatus

Lysosome

Nucleus

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<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

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<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

Amino acid modifications

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ