TISIDB

Summary
Symbol	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
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. Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Cytoplasmic and nuclear in the absence of ligand; nuclear after ligand-binding. When bound to HSD11B2, it is found associated with the endoplasmic reticulum membrane.
Domain	PF00104 Ligand-binding domain of nuclear hormone receptor PF00105 Zinc finger
Function	Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.

> Gene Ontology [ TOP ]
Biological Process	GO:0006352 DNA-templated transcription, initiation GO:0006367 transcription initiation from RNA polymerase II promoter GO:0009755 hormone-mediated signaling pathway GO:0043401 steroid hormone mediated signaling pathway GO:0048545 response to steroid hormone GO:0071383 cellular response to steroid hormone stimulus GO:0071396 cellular response to lipid GO:0071407 cellular response to organic cyclic compound
Molecular Function	GO:0003707 steroid hormone receptor activity GO:0005496 steroid binding
Cellular Component	GO:0043235 receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04960 Aldosterone-regulated sodium reabsorption
Reactome	R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-383280: Nuclear Receptor transcription pathway

Summary
Symbol	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NR3C2 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 NR3C2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
16920987	pancreatic carcinoma	Promote immunity	Medium conditioned by human pancreatic carcinoma cells inhibited iMo-DC proliferation, expression of costimulatory molecules (CD80 and CD40) and of HLA-DR, and functional activity as assessed by MLR and IL-12p70 production. iMo-DC generated from pancreatic carcinoma patients in advanced stages of the disease similarly showed decreased levels of HLA-DR expression and reduced ability to stimulate MLR in response to CD40L and IFN-gamma.

Summary
Symbol	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
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 NR3C2 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	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
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 NR3C2 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	0.464	0.108
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.407	0.42
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.514	0.22
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.454	0.303
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.348	0.865
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.579	0.804
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.377	0.395
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.395	0.0779
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.84	0.374
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.591	0.256
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	0.078	0.903
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.039	0.842

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of NR3C2 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	3.7	4.1	-0.4	1
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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	11.8	-2.3	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	7.7	18.2	-10.5	0.576
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	13.2	0	13.2	0.0705
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	22.7	0	22.7	0.134
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
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	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NR3C2. 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	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NR3C2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NR3C2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NR3C2. 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	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NR3C2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NR3C2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NR3C2
Name	nuclear receptor subfamily 3, group C, member 2
Aliases	MR; MLR; MCR; MRVIT; aldosterone receptor; mineralocorticoid receptor 1; mineralocorticoid receptor 2; miner ......
Chromosomal Location	4q31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NR3C2 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting NR3C2.

ID	Name	Drug Type	Targets	#Targets
DB00393	Nimodipine	Small Molecule	AHR, CACNA1C, CACNA1D, CACNA1F, CACNA1S, CACNB1, CACNB2, CACNB3, C ......	10
DB00396	Progesterone	Small Molecule	AR, CYP17A1, ESR1, NR1I2, NR3C1, NR3C2, OPRK1, ORM1, PGR, SHBG	10
DB00421	Spironolactone	Small Molecule	AR, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1F, CACNA1G, CACNA1H, ......	27
DB00588	Fluticasone propionate	Small Molecule	NR3C1, NR3C2, PGR, PLA2G4A	4
DB00624	Testosterone	Small Molecule	AR, ESR1, NR3C2	3
DB00687	Fludrocortisone	Small Molecule	AR, NR3C1, NR3C2	3
DB00700	Eplerenone	Small Molecule	NR3C2	1
DB01023	Felodipine	Small Molecule	CACNA1C, CACNA1D, CACNA1H, CACNA1S, CACNA2D1, CACNA2D2, CACNB2, NR ......	12
DB01134	Desoxycorticosterone Pivalate	Small Molecule	NR3C2	1
DB01395	Drospirenone	Small Molecule	AR, NR3C2, PGR	3
DB02901	Stanolone	Small Molecule	AR, ESR1, HSD17B1, NR3C2	4
DB02998	Methyltrienolone	Small Molecule	AR, NCOA2, NR3C2, PGR	4
DB04630	Aldosterone	Small Molecule	NR3C1, NR3C2	2
DB04652	Corticosterone	Small Molecule	HSD11B1, NCOA1, NR3C2	3
DB06780	Desoxycorticosterone acetate	Small Molecule	NR3C2	1
DB13943	Testosterone cypionate	Small Molecule	AR, ESR1, NR3C2	3
DB13944	Testosterone enanthate	Small Molecule	AR, ESR1, NR3C2	3
DB13946	Testosterone undecanoate	Small Molecule	AR, ESR1, NR3C2	3
DB13951	Stanolone acetate	Small Molecule	AR, ESR1, HSD17B1, NR3C2	4

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