TISIDB

Summary
Symbol	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
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	Membrane Single-pass type I membrane protein Cytoplasmic vesicle membrane Single-pass type I membrane protein Melanosome Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Domain	PF05450 Nicastrin
Function	Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.

> Gene Ontology [ TOP ]
Biological Process	GO:0002262 myeloid cell homeostasis GO:0006509 membrane protein ectodomain proteolysis GO:0007159 leukocyte cell-cell adhesion GO:0007219 Notch signaling pathway GO:0007220 Notch receptor processing GO:0016485 protein processing GO:0031293 membrane protein intracellular domain proteolysis GO:0032943 mononuclear cell proliferation GO:0033619 membrane protein proteolysis GO:0042098 T cell proliferation GO:0042110 T cell activation GO:0042982 amyloid precursor protein metabolic process GO:0042987 amyloid precursor protein catabolic process GO:0046651 lymphocyte proliferation GO:0048013 ephrin receptor signaling pathway GO:0048872 homeostasis of number of cells GO:0050435 beta-amyloid metabolic process GO:0050673 epithelial cell proliferation GO:0051604 protein maturation GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0071593 lymphocyte aggregation
Molecular Function	GO:0004175 endopeptidase activity
Cellular Component	GO:0005765 lysosomal membrane GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction GO:0042470 melanosome GO:0048770 pigment granule GO:0098852 lytic vacuole membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04330 Notch signaling pathway
Reactome	R-HSA-157212: A third proteolytic cleavage releases NICD R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-422475: Axon guidance R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-1474228: Degradation of the extracellular matrix R-HSA-1266738: Developmental Biology R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-2682334: EPH-Ephrin signaling R-HSA-3928665: EPH-ephrin mediated repulsion of cells R-HSA-1474244: Extracellular matrix organization R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-2979096: NOTCH2 Activation and Transmission of Signal to the Nucleus R-HSA-205043: NRIF signals cell death from the nucleus R-HSA-6798695: Neutrophil degranulation R-HSA-1251985: Nuclear signaling by ERBB4 R-HSA-193692: Regulated proteolysis of p75NTR R-HSA-162582: Signal Transduction R-HSA-1236394: Signaling by ERBB4 R-HSA-157118: Signaling by NOTCH R-HSA-1980143: Signaling by NOTCH1 R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2644603: Signaling by NOTCH1 in Cancer R-HSA-1980145: Signaling by NOTCH2 R-HSA-1980148: Signaling by NOTCH3 R-HSA-1980150: Signaling by NOTCH4 R-HSA-166520: Signalling by NGF R-HSA-193704: p75 NTR receptor-mediated signalling

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04330 Notch signaling pathway

Reactome

R-HSA-157212: A third proteolytic cleavage releases NICD
R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-422475: Axon guidance
R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1474228: Degradation of the extracellular matrix
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2682334: EPH-Ephrin signaling
R-HSA-3928665: EPH-ephrin mediated repulsion of cells
R-HSA-1474244: Extracellular matrix organization
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-2979096: NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-205043: NRIF signals cell death from the nucleus
R-HSA-6798695: Neutrophil degranulation
R-HSA-1251985: Nuclear signaling by ERBB4
R-HSA-193692: Regulated proteolysis of p75NTR
R-HSA-162582: Signal Transduction
R-HSA-1236394: Signaling by ERBB4
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer
R-HSA-1980145: Signaling by NOTCH2
R-HSA-1980148: Signaling by NOTCH3
R-HSA-1980150: Signaling by NOTCH4
R-HSA-166520: Signalling by NGF
R-HSA-193704: p75 NTR receptor-mediated signalling

Summary
Symbol	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NCSTN 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 [ TOP ]
There is no record.

Summary
Symbol	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
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

[ TOP ]

Statistical results of NCSTN 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	STARS Score: 4.80; FDR: 0.004	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 6.01; FDR: 0.001	Resistant to T cell-mediated killing
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	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
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

[ TOP ]

Points in the above scatter plot represent the expression difference of NCSTN 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	-0.056	0.822
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.231	0.933
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.072	0.971
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.378	0.272
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.281	0.89
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.507	0.854
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.168	0.702
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.079	0.968
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.418	0.852
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.546	0.776
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	1.007	0.729
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.334	1.04e-05

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of NCSTN 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	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
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	5.9	-5.9	0.447
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	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	11.1	-11.1	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	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NCSTN. 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	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NCSTN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NCSTN. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NCSTN. 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	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NCSTN expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NCSTN and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NCSTN
Name	nicastrin
Aliases	KIAA0253; ATAG1874; anterior pharynx-defective 2
Chromosomal Location	1q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NCSTN collected from DrugBank database.

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

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