NPC2 NPC intracellular cholesterol transporter 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPC2provided by HGNC
Official Full Name: NPC intracellular cholesterol transporter 2provided by HGNC
Primary source: HGNC:HGNC:14537
See related: Ensembl:ENSG00000119655 MIM:601015; AllianceGenome:HGNC:14537
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: HE1; EDDM1
Summary: This gene encodes a protein containing a lipid recognition domain. The encoded protein may function in regulating the transport of cholesterol through the late endosomal/lysosomal system. Mutations in this gene have been associated with Niemann-Pick disease, type C2 and frontal lobe atrophy. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in lung (RPKM 202.8), thyroid (RPKM 113.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q24.3

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (74479935..74493512, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (68688905..68702483, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (74946638..74960215, complement)

Chromosome 14 - NC_000014.9 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: 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?

Increase in plasma Niemann-Pick disease type C2 protein is associated with poor prognosis of sepsis.
Title: Increase in plasma Niemann-Pick disease type C2 protein is associated with poor prognosis of sepsis.
Niemann-Pick Type C 1 (NPC1) and NPC2 Gene Variability in Demented Patients with Evidence of Brain Amyloid Deposition.
Title: Niemann-Pick Type C 1 (NPC1) and NPC2 Gene Variability in Demented Patients with Evidence of Brain Amyloid Deposition.
Transcriptomic Biomarkers for Tuberculosis: Validation of NPC2 as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response.
Title: Transcriptomic Biomarkers for Tuberculosis: Validation of NPC2 as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response.
Identification and Classification of Rare Variants in NPC1 and NPC2 in Quebec.
Title: Identification and Classification of Rare Variants in NPC1 and NPC2 in Quebec.
Secretory NPC2 Protein-Mediated Free Cholesterol Levels Were Correlated with the Sorafenib Response in Hepatocellular Carcinoma.
Title: Secretory NPC2 Protein-Mediated Free Cholesterol Levels Were Correlated with the Sorafenib Response in Hepatocellular Carcinoma.
Niemann Pick C2 protein enables cholesterol transfer from endo-lysosomes to the plasma membrane for efflux by shedding of extracellular vesicles.
Title: Niemann Pick C2 protein enables cholesterol transfer from endo-lysosomes to the plasma membrane for efflux by shedding of extracellular vesicles.
Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2.
Title: Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2.
New variant associated with Niemann-Pick disease type C: Neurological manifestations and biochemical, molecular, and cellular characterisation.", trans "Nueva variante asociada a enfermedad de Niemann-Pick tipo C: manifestaciones neurologicas y caracterizacion bioquimica, molecular y celular.
Title: New variant associated with Niemann-Pick disease type C: Neurological manifestations and biochemical, molecular, and cellular characterisation.
conclude that NPC2's affinity for all sterols is energetically favored over their self-aggregation in the lysosomal lumen. Lysosomal export of 25-OH-Chol is not strictly dependent on the NPC2 protein.
Title: Binding and intracellular transport of 25-hydroxycholesterol by Niemann-Pick C2 protein.
The authors demonstrate that lysobisphosphatidic acid enrichment in human NPC2-deficient cells, either directly or via its biosynthetic precursor phosphtidylglycerol (PG), is entirely ineffective, indicating an obligate functional interaction between NPC2 and lysobisphosphatidic acid in cholesterol trafficking.
Title: Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid.

Submit: New GeneRIF Correction See all GeneRIFs (68)

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 C2 MedGen: C1843366 OMIM: 607625 GeneReviews: Niemann-Pick Disease Type C	Compare labs

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

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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

SHGC-12718 (e-PCR)
- UniSTS:28769

G38283 (e-PCR)
- UniSTS:39800

RH65075 (e-PCR)
- UniSTS:85120

RH70872 (e-PCR)
- UniSTS:45706

SHGC-132103 (e-PCR)
- UniSTS:170649

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 cholesterol transfer activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cholesterol efflux	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol efflux	IDA Inferred from Direct Assay more info	PubMed
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 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 gene expression	IEA Inferred from Electronic Annotation more info
involved_in glycolipid transport	TAS Traceable Author Statement more info	PubMed
involved_in intermembrane lipid transfer	IEA Inferred from Electronic Annotation more info
involved_in intracellular cholesterol transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular cholesterol transport	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within intracellular cholesterol transport	IGI Inferred from Genetic Interaction more info	PubMed
involved_in intracellular cholesterol transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular sterol transport	IDA Inferred from Direct Assay more info	PubMed
involved_in phospholipid transport	TAS Traceable Author Statement more info	PubMed
involved_in regulation of isoprenoid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in response to virus	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in azurophil granule lumen	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IMP Inferred from Mutant Phenotype more info	PubMed
located_in lysosomal lumen	TAS Traceable Author Statement more info
is_active_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NPC intracellular cholesterol transporter 2

Names: Niemann-Pick disease type C2 protein; epididymal protein 1; epididymis secretory sperm binding protein; human epididymis-specific protein 1; tissue-specific secretory 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_007117.1 RefSeqGene

Range

5077..18442

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001363688.1 → NP_001350617.1 NPC intracellular cholesterol transporter 2 isoform 1 precursor

Status: REVIEWED

Source sequence(s)

AC005479, CB265591

Consensus CDS

CCDS86413.1

UniProtKB/TrEMBL

B2R4S5, G3V3E8

Related

ENSP00000451206.1, ENST00000557510.5

Conserved Domains (1) summary

cd00916
Location:24 → 145

Npc2_like; Niemann-Pick type C2 (Npc2) is a lysosomal protein in which a mutation in the gene causes a rare form of Niemann-Pick type C disease, an autosomal recessive lipid storage disorder characterized by accumulation of low-density lipoprotein-derived ...
NM_001375440.1 → NP_001362369.1 NPC intracellular cholesterol transporter 2 isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AK298975, GQ891387

Consensus CDS

CCDS91904.1

UniProtKB/TrEMBL

G3V2V8

Related

ENSP00000442488.1, ENST00000541064.5

Conserved Domains (1) summary

cd00916
Location:24 → 123

Npc2_like; Niemann-Pick type C2 (Npc2) is a lysosomal protein in which a mutation in the gene causes a rare form of Niemann-Pick type C disease, an autosomal recessive lipid storage disorder characterized by accumulation of low-density lipoprotein-derived ...
NM_006432.5 → NP_006423.1 NPC intracellular cholesterol transporter 2 isoform 2 precursor

See identical proteins and their annotated locations for NP_006423.1

Status: REVIEWED

Source sequence(s)

GQ891387

Consensus CDS

CCDS32121.1

UniProtKB/Swiss-Prot

B4DQV7, P61916, Q15668, Q29413

UniProtKB/TrEMBL

A0A024R6C0, B2R4S5

Related

ENSP00000451112.2, ENST00000555619.6

Conserved Domains (1) summary

cd00916
Location:24 → 145

Npc2_like; Niemann-Pick type C2 (Npc2) is a lysosomal protein in which a mutation in the gene causes a rare form of Niemann-Pick type C disease, an autosomal recessive lipid storage disorder characterized by accumulation of low-density lipoprotein-derived ...