Browse NPC2

Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted Endoplasmic reticulum Lysosome
Domain PF02221 ML domain
Function

Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular 'tag team duo' (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport.

> Gene Ontology
 
Biological Process GO:0006066 alcohol metabolic process
GO:0006720 isoprenoid metabolic process
GO:0006869 lipid transport
GO:0008202 steroid metabolic process
GO:0008203 cholesterol metabolic process
GO:0009615 response to virus
GO:0010876 lipid localization
GO:0015748 organophosphate ester transport
GO:0015850 organic hydroxy compound transport
GO:0015914 phospholipid transport
GO:0015918 sterol transport
GO:0016125 sterol metabolic process
GO:0019216 regulation of lipid metabolic process
GO:0019747 regulation of isoprenoid metabolic process
GO:0030301 cholesterol transport
GO:0032365 intracellular lipid transport
GO:0032366 intracellular sterol transport
GO:0032367 intracellular cholesterol transport
GO:0033344 cholesterol efflux
GO:0042632 cholesterol homeostasis
GO:0046836 glycolipid transport
GO:0055088 lipid homeostasis
GO:0055092 sterol homeostasis
GO:1901264 carbohydrate derivative transport
GO:1901615 organic hydroxy compound metabolic process
GO:1902652 secondary alcohol metabolic process
Molecular Function GO:0005496 steroid binding
GO:0015485 cholesterol binding
GO:0032934 sterol binding
GO:0043178 alcohol binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04142 Lysosome
Reactome R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-171052: LDL-mediated lipid transport
R-HSA-73923: Lipid digestion, mobilization, and transport
R-HSA-174824: Lipoprotein metabolism
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-6798695: Neutrophil degranulation
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NPC2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between NPC2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26183450Lung CarcinomaPromote immunityStromal immature macrophage-lineage cells (IMCs) promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer.
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of NPC2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of NPC2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0740.815
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2280.956
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0390.99
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3290.368
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.150.944
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.9350.734
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.3840.415
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.470.814
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.3720.873
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3760.887
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7610.854
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1940.0305
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of NPC2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103033.3-33.30.231
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NPC2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NPC2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NPC2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NPC2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NPC2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NPC2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNPC2
NameNiemann-Pick disease, type C2
Aliases HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location14q24.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NPC2 collected from DrugBank database.
> Drugs from DrugBank database
 

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