TISIDB

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
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

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Literatures describing the relation between NPC2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26183450	Lung Carcinoma	Promote immunity	Stromal 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
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.074	0.815
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.228	0.956
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.039	0.99
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.329	0.368
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.15	0.944
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.935	0.734
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.384	0.415
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.47	0.814
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.372	0.873
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.376	0.887
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.761	0.854
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.194	0.0305

> Mutation difference between responders and non-responders

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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/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	33.3	-33.3	0.231
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
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 [ TOP ]

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NPC2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NPC2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NPC2
Name	Niemann-Pick disease, type C2
Aliases	HE1; NP-C2; EDDM1; epididymal protein 1; Niemann-Pick disease type C2 protein; human epididymis-specific pro ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NPC2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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