TISIDB

Summary
Symbol	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
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	Cytoplasm Nucleus Note=Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals. The subcellular localization of NFATC plays a key role in the regulation of gene transcription (PubMed:16511445). Nuclear translocation of NFATC1 is enhanced in the presence of TNFSF11. Nuclear translocation is decreased in the presence of FBN1 which can bind and sequester TNFSF11 (By similarity).
Domain	PF16179 Rel homology dimerisation domain PF00554 Rel homology DNA-binding domain
Function	Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0007223 Wnt signaling pathway, calcium modulating pathway GO:0016055 Wnt signaling pathway GO:0019722 calcium-mediated signaling GO:0019932 second-messenger-mediated signaling GO:0030111 regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0033173 calcineurin-NFAT signaling cascade GO:0035567 non-canonical Wnt signaling pathway GO:0038093 Fc receptor signaling pathway GO:0038095 Fc-epsilon receptor signaling pathway GO:0048016 inositol phosphate-mediated signaling GO:0097720 calcineurin-mediated signaling GO:0198738 cell-cell signaling by wnt
Molecular Function	GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding GO:0001085 RNA polymerase II transcription factor binding GO:0001158 enhancer sequence-specific DNA binding GO:0001205 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding GO:0001221 transcription cofactor binding GO:0001223 transcription coactivator binding GO:0001224 RNA polymerase II transcription cofactor binding GO:0001225 RNA polymerase II transcription coactivator binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0005527 macrolide binding GO:0005528 FK506 binding GO:0008134 transcription factor binding GO:0008144 drug binding GO:0035326 enhancer binding GO:0048273 mitogen-activated protein kinase p38 binding GO:0051019 mitogen-activated protein kinase binding
Cellular Component	GO:0000785 chromatin GO:0000790 nuclear chromatin GO:0044454 nuclear chromosome part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04022 cGMP-PKG signaling pathway hsa04024 cAMP signaling pathway hsa04310 Wnt signaling pathway hsa04380 Osteoclast differentiation hsa04650 Natural killer cell mediated cytotoxicity hsa04660 T cell receptor signaling pathway hsa04662 B cell receptor signaling pathway hsa04921 Oxytocin signaling pathway
Reactome	R-HSA-3858494: Beta-catenin independent WNT signaling R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-5607763: CLEC7A (Dectin-1) induces NFAT activation R-HSA-5607764: CLEC7A (Dectin-1) signaling R-HSA-4086398: Ca2+ pathway R-HSA-2871809: FCERI mediated Ca+2 mobilization R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-162582: Signal Transduction R-HSA-195721: Signaling by Wnt

> KEGG and Reactome Pathway

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KEGG

hsa04010 MAPK signaling pathway
hsa04022 cGMP-PKG signaling pathway
hsa04024 cAMP signaling pathway
hsa04310 Wnt signaling pathway
hsa04380 Osteoclast differentiation
hsa04650 Natural killer cell mediated cytotoxicity
hsa04660 T cell receptor signaling pathway
hsa04662 B cell receptor signaling pathway
hsa04921 Oxytocin signaling pathway

Reactome

R-HSA-3858494: Beta-catenin independent WNT signaling
R-HSA-5621481: C-type lectin receptors (CLRs)
R-HSA-5607763: CLEC7A (Dectin-1) induces NFAT activation
R-HSA-5607764: CLEC7A (Dectin-1) signaling
R-HSA-4086398: Ca2+ pathway
R-HSA-2871809: FCERI mediated Ca+2 mobilization
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-162582: Signal Transduction
R-HSA-195721: Signaling by Wnt

Summary
Symbol	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NFATC1 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 NFATC1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25851535	Melanoma	Inhibit immunity (T cell function)	Together, we propose that targeting the unrecognized ADAP-SKAP55-NFATc1-PD-1 pathway might increase efficacy of anti-tumor immunotherapy.

Summary
Symbol	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
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 NFATC1 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	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
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 NFATC1 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	0.46	0.241
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.143	0.913
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.894	0.413
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.289	0.615
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.386	0.86
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.162	0.955
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.439	0.242
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.667	0.554
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.114	0.932
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.159	0.285
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	1.693	0.266
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.186	0.231

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of NFATC1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	11.1	1.4	9.7	0.0589
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	1.7	9.4	0.0895
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NFATC1. 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	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NFATC1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NFATC1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NFATC1. 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	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NFATC1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NFATC1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NFATC1
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases	NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location	18q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NFATC1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting NFATC1.

ID	Name	Drug Type	Targets	#Targets
DB00852	Pseudoephedrine	Small Molecule	ADRA1A, ADRA2A, ADRB1, ADRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ......	20

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