NPC1 NPC intracellular cholesterol transporter 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPC1provided by HGNC
Official Full Name: NPC intracellular cholesterol transporter 1provided by HGNC
Primary source: HGNC:HGNC:7897
See related: Ensembl:ENSG00000141458 MIM:607623; AllianceGenome:HGNC:7897
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NPC; POGZ; SLC65A1
Summary: 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]
Expression: Ubiquitous expression in adrenal (RPKM 13.9), brain (RPKM 10.0) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 18q11.2

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (23506184..23586506, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (23700273..23780767, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (21111406..21166470, complement)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Familial Alzheimer's disease associated with heterozygous NPC1 mutation.
Title: Familial Alzheimer's disease associated with heterozygous NPC1 mutation.
NPC1 promotes autophagy with tumor promotion and acts as a prognostic model for hepatocellular carcinoma.
Title: NPC1 promotes autophagy with tumor promotion and acts as a prognostic model for hepatocellular carcinoma.
NPC1 plays a role in the trafficking of specific cargo to melanosomes.
Title: NPC1 plays a role in the trafficking of specific cargo to melanosomes.
NPC1-dependent alterations in KV2.1-CaV1.2 nanodomains drive neuronal death in models of Niemann-Pick Type C disease.
Title: NPC1-dependent alterations in K(V)2.1-Ca(V)1.2 nanodomains drive neuronal death in models of Niemann-Pick Type C disease.
A Novel Small NPC1 Promoter Enhances AAV-Mediated Gene Therapy in Mouse Models of Niemann-Pick Type C1 Disease.
Title: A Novel Small NPC1 Promoter Enhances AAV-Mediated Gene Therapy in Mouse Models of Niemann-Pick Type C1 Disease.
NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts.
Title: NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts.
Purification and structure of luminal domain C of human Niemann-Pick C1 protein.
Title: Purification and structure of luminal domain C of human Niemann-Pick C1 protein.
CRISPR-Cas9-Mediated NPC1 Gene Deletion Enhances HEK 293 T Cell Adhesion by Regulating E-Cadherin.
Title: CRISPR-Cas9-Mediated NPC1 Gene Deletion Enhances HEK 293 T Cell Adhesion by Regulating E-Cadherin.
The point mutation of the cholesterol trafficking membrane protein NPC1 may affect its proper function in more than a single step: Molecular dynamics simulation study.
Title: The point mutation of the cholesterol trafficking membrane protein NPC1 may affect its proper function in more than a single step: Molecular dynamics simulation study.
Whole-exome sequencing analysis to identify novel potential pathogenetic NPC1 mutations in two Chinese families with Niemann-Pick disease type C.
Title: Whole-exome sequencing analysis to identify novel potential pathogenetic NPC1 mutations in two Chinese families with Niemann-Pick disease type C.

Submit: New GeneRIF Correction See all GeneRIFs (166)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Niemann-Pick disease, type C1 MedGen: C3179455 OMIM: 257220 GeneReviews: Niemann-Pick Disease Type C	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	NPC2-deficient cells exhibit Gag accumulation in late endosomal/lysosomal (LE/L) compartments of these cells as well as decreased NPC1 expression after HIV infection	PubMed
	gag	Niemann-Pick type C-1 (NPC1)-deficient (NPCD) cells exhibit few HIV-1 budding events. HIV-1 Gag accumulates in late endosomal/lysosomal (LE/L) compartments in NPCD cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D18S1243 (e-PCR)
- UniSTS:68454

NPC1_s22 (e-PCR)
- UniSTS:512126

WI-14881 (e-PCR)
- UniSTS:60833

RH11988 (e-PCR)
- UniSTS:40637

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cholesterol binding	IBA Inferred from Biological aspect of Ancestor more info
enables cholesterol binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	TAS Traceable Author Statement more info	PubMed
enables transmembrane signaling receptor activity	TAS Traceable Author Statement more info	PubMed
enables virus receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in adult walking behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within autophagy	IGI Inferred from Genetic Interaction more info	PubMed
involved_in bile acid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to low-density lipoprotein particle stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to steroid hormone stimulus	IEA Inferred from Electronic Annotation more info
involved_in cholesterol efflux	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in cholesterol storage	IEA Inferred from Electronic Annotation more info
involved_in cholesterol transport	IDA Inferred from Direct Assay more info	PubMed
involved_in cyclodextrin metabolic process	IEA Inferred from Electronic Annotation more info
involved_in endocytosis	IEA Inferred from Electronic Annotation more info
involved_in establishment of protein localization to membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in intestinal cholesterol absorption	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular cholesterol transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular lipid transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in lysosomal transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in macroautophagy	IEA Inferred from Electronic Annotation more info
involved_in membrane raft organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of epithelial cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of macroautophagy	IEA Inferred from Electronic Annotation more info
involved_in neurogenesis	IEA Inferred from Electronic Annotation more info
involved_in programmed cell death	IEA Inferred from Electronic Annotation more info
involved_in protein glycosylation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in symbiont entry into host cell	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	ISS Inferred from Sequence or Structural Similarity more info
located_in late endosome membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in lysosomal membrane	HDA more info	PubMed
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in lysosomal membrane	TAS Traceable Author Statement more info
located_in lysosome	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	HDA more info	PubMed
located_in membrane raft	IEA Inferred from Electronic Annotation more info
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NPC intracellular cholesterol transporter 1

Names: Niemann-Pick C1 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012795.2 RefSeqGene

Range

5000..60064

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000271.5 → NP_000262.2 NPC intracellular cholesterol transporter 1 precursor

See identical proteins and their annotated locations for NP_000262.2

Status: REVIEWED

Source sequence(s)

AB209048, AC010853, AF002020, BC063302, DR159421

Consensus CDS

CCDS11878.1

UniProtKB/Swiss-Prot

B4DET3, O15118, Q9P130

UniProtKB/TrEMBL

A0A193DRS0

Related

ENSP00000269228.4, ENST00000269228.10

Conserved Domains (1) summary

TIGR00917
Location:25 → 1252

2A060601; Niemann-Pick C type protein family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000018.10 Reference GRCh38.p14 Primary Assembly

Range

23506184..23586506 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005258279.3 → XP_005258336.1 NPC intracellular cholesterol transporter 1 isoform X3

UniProtKB/TrEMBL

A0A193DRS0

Conserved Domains (3) summary

TIGR00917
Location:25 → 1251

2A060601; Niemann-Pick C type protein family

pfam12349
Location:649 → 802

Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation

pfam16414
Location:23 → 267

NPC1_N; Niemann-Pick C1 N terminus
XM_005258277.1 → XP_005258334.1 NPC intracellular cholesterol transporter 1 isoform X1

UniProtKB/TrEMBL

A0A193DRS0

Conserved Domains (3) summary

TIGR00917
Location:25 → 1268

2A060601; Niemann-Pick C type protein family

pfam12349
Location:666 → 819

Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation

pfam16414
Location:23 → 267

NPC1_N; Niemann-Pick C1 N terminus
XM_017025787.2 → XP_016881276.1 NPC intracellular cholesterol transporter 1 isoform X8

UniProtKB/TrEMBL

A0A193DRS0
XM_006722479.4 → XP_006722542.1 NPC intracellular cholesterol transporter 1 isoform X5

UniProtKB/TrEMBL

A0A193DRS0

Conserved Domains (3) summary

TIGR00917
Location:25 → 1269

2A060601; Niemann-Pick C type protein family

pfam12349
Location:666 → 819

Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation

pfam16414
Location:23 → 267

NPC1_N; Niemann-Pick C1 N terminus
XM_047437539.1 → XP_047293495.1 NPC intracellular cholesterol transporter 1 isoform X9
XM_017025786.2 → XP_016881275.1 NPC intracellular cholesterol transporter 1 isoform X7

UniProtKB/TrEMBL

A0A193DRS0
XM_017025785.1 → XP_016881274.1 NPC intracellular cholesterol transporter 1 isoform X6

UniProtKB/TrEMBL

A0A193DRS0
XM_017025784.1 → XP_016881273.1 NPC intracellular cholesterol transporter 1 isoform X4

UniProtKB/TrEMBL

A0A193DRS0
XM_005258278.6 → XP_005258335.1 NPC intracellular cholesterol transporter 1 isoform X2

UniProtKB/TrEMBL

A0A193DRS0

Conserved Domains (3) summary

TIGR00917
Location:25 → 1269

2A060601; Niemann-Pick C type protein family

pfam12349
Location:666 → 819

Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation

pfam16414
Location:23 → 267

NPC1_N; Niemann-Pick C1 N terminus

Alternate T2T-CHM13v2.0

Genomic

NC_060942.1 Alternate T2T-CHM13v2.0

Range

23700273..23780767 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054318666.1 → XP_054174641.1 NPC intracellular cholesterol transporter 1 isoform X3
XM_054318664.1 → XP_054174639.1 NPC intracellular cholesterol transporter 1 isoform X1
XM_054318671.1 → XP_054174646.1 NPC intracellular cholesterol transporter 1 isoform X8
XM_054318668.1 → XP_054174643.1 NPC intracellular cholesterol transporter 1 isoform X5
XM_054318672.1 → XP_054174647.1 NPC intracellular cholesterol transporter 1 isoform X9
XM_054318670.1 → XP_054174645.1 NPC intracellular cholesterol transporter 1 isoform X7
XM_054318669.1 → XP_054174644.1 NPC intracellular cholesterol transporter 1 isoform X6
XM_054318667.1 → XP_054174642.1 NPC intracellular cholesterol transporter 1 isoform X4
XM_054318665.1 → XP_054174640.1 NPC intracellular cholesterol transporter 1 isoform X2