NPC1L1 NPC1 like intracellular cholesterol transporter 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPC1L1provided by HGNC
Official Full Name: NPC1 like intracellular cholesterol transporter 1provided by HGNC
Primary source: HGNC:HGNC:7898
See related: Ensembl:ENSG00000015520 MIM:608010; AllianceGenome:HGNC:7898
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: LDLCQ7; NPC11L1; SLC65A2
Summary: The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Expression: Biased expression in duodenum (RPKM 24.2), small intestine (RPKM 22.9) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7p13

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (44512535..44541330, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (44672255..44701030, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (44552134..44580929, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NPC1L1 rs217434 A > G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population.
Title: NPC1L1 rs217434 A > G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population.
Cholesterol uptake in the intestine is regulated by the LASP1-AKT-NPC1L1 signaling pathway.
Title: Cholesterol uptake in the intestine is regulated by the LASP1-AKT-NPC1L1 signaling pathway.
Association of NPC1L1 and HMGCR gene polymorphisms with coronary artery calcification in patients with premature triple-vessel coronary disease.
Title: Association of NPC1L1 and HMGCR gene polymorphisms with coronary artery calcification in patients with premature triple-vessel coronary disease.
HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.
Title: HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.
m6A-related bioinformatics analysis and functional characterization reveals that METTL3-mediated NPC1L1 mRNA hypermethylation facilitates progression of atherosclerosis via inactivation of the MAPK pathway.
Title: m6A-related bioinformatics analysis and functional characterization reveals that METTL3-mediated NPC1L1 mRNA hypermethylation facilitates progression of atherosclerosis via inactivation of the MAPK pathway.
Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.
Title: Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.
Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease.
Title: Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease.
Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study.
Title: Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study.
NPC1L1-dependent transport of 27-alkyne cholesterol in intestinal epithelial cells.
Title: NPC1L1-dependent transport of 27-alkyne cholesterol in intestinal epithelial cells.
The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity.
Title: The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity.

Submit: New GeneRIF Correction See all GeneRIFs (98)

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

EBI GWAS Catalog

Description
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH46066 (e-PCR)
- UniSTS:4002

D7S2697 (e-PCR)
- UniSTS:73413

SGC38249 (e-PCR)
- UniSTS:65992

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 myosin V binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables small GTPase binding	IPI Inferred from Physical Interaction more info	PubMed
enables vitamin E binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to sterol depletion	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intestinal cholesterol absorption	IBA Inferred from Biological aspect of Ancestor more info
involved_in intestinal cholesterol absorption	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lipoprotein metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sterol transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in vitamin E metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in vitamin transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic vesicle membrane	IEA Inferred from Electronic Annotation more info
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
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: NPC1-like intracellular cholesterol transporter 1

Names: NPC1 (Niemann-Pick disease, type C1, gene)-like 1; NPC1 like 1; niemann-Pick C1-like protein 1

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_013088.1 RefSeqGene

Range

4986..33781

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001101648.2 → NP_001095118.1 NPC1-like intracellular cholesterol transporter 1 isoform 2 precursor

See identical proteins and their annotated locations for NP_001095118.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AC004938, AF192522, AY515256

Consensus CDS

CCDS43575.1

UniProtKB/TrEMBL

A0A0C4DFX6, A0A0C4DGG6

Related

ENSP00000370552.3, ENST00000381160.8

Conserved Domains (3) summary

TIGR00917
Location:33 → 1266

2A060601; Niemann-Pick C type protein family

pfam12349
Location:661 → 814

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

pfam16414
Location:31 → 283

NPC1_N; Niemann-Pick C1 N terminus
NM_001300967.2 → NP_001287896.1 NPC1-like intracellular cholesterol transporter 1 isoform 3 precursor

See identical proteins and their annotated locations for NP_001287896.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks several exons and its 3'-terminal exon extends past a splice site that is used in variant 1. The encoded isoform (3) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC004938, AF192523

Consensus CDS

CCDS75587.1

UniProtKB/Swiss-Prot

Q9UHC9

Related

ENSP00000404670.1, ENST00000423141.1

Conserved Domains (3) summary

TIGR00917
Location:33 → 722

2A060601; Niemann-Pick C type protein family

pfam16414
Location:31 → 283

NPC1_N; Niemann-Pick C1 N terminus

cl21543
Location:661 → 722

MMPL; MMPL family
NM_013389.3 → NP_037521.2 NPC1-like intracellular cholesterol transporter 1 isoform 1 precursor

See identical proteins and their annotated locations for NP_037521.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC004938, AF192522

Consensus CDS

CCDS5491.1

UniProtKB/Swiss-Prot

A4D2J7, B7ZLE6, D3DVK9, Q17RV5, Q6R3Q4, Q9UHC8, Q9UHC9

UniProtKB/TrEMBL

A0A0C4DGG6

Related

ENSP00000289547.4, ENST00000289547.8

Conserved Domains (3) summary

TIGR00917
Location:33 → 1293

2A060601; Niemann-Pick C type protein family

pfam12349
Location:661 → 814

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

pfam16414
Location:31 → 283

NPC1_N; Niemann-Pick C1 N terminus

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

44512535..44541330 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011515326.4 → XP_011513628.1 NPC1-like intracellular cholesterol transporter 1 isoform X1

UniProtKB/TrEMBL

A0A0C4DGG6

Conserved Domains (3) summary

TIGR00917
Location:33 → 1201

2A060601; Niemann-Pick C type protein family

pfam16414
Location:31 → 283

NPC1_N; Niemann-Pick C1 N terminus

cl21543
Location:661 → 749

MMPL; MMPL family
XM_011515328.3 → XP_011513630.1 NPC1-like intracellular cholesterol transporter 1 isoform X3

Conserved Domains (2) summary

TIGR00917
Location:71 → 719

2A060601; Niemann-Pick C type protein family

pfam12349
Location:114 → 267

Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
XM_047420280.1 → XP_047276236.1 NPC1-like intracellular cholesterol transporter 1 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060931.1 Alternate T2T-CHM13v2.0

Range

44672255..44701030 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054358018.1 → XP_054213993.1 NPC1-like intracellular cholesterol transporter 1 isoform X1

UniProtKB/TrEMBL

A0A0C4DGG6
XM_054358020.1 → XP_054213995.1 NPC1-like intracellular cholesterol transporter 1 isoform X3
XM_054358019.1 → XP_054213994.1 NPC1-like intracellular cholesterol transporter 1 isoform X2