TISIDB

Summary
Symbol	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
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	Nucleus
Domain	PF00104 Ligand-binding domain of nuclear hormone receptor PF00105 Zinc finger
Function	Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC).

> Gene Ontology [ TOP ]
Biological Process	GO:0006352 DNA-templated transcription, initiation GO:0006367 transcription initiation from RNA polymerase II promoter GO:0007623 circadian rhythm GO:0009266 response to temperature stimulus GO:0009314 response to radiation GO:0009416 response to light stimulus GO:0009581 detection of external stimulus GO:0009582 detection of abiotic stimulus GO:0009648 photoperiodism GO:0009649 entrainment of circadian clock GO:0009755 hormone-mediated signaling pathway GO:0016048 detection of temperature stimulus GO:0019233 sensory perception of pain GO:0030522 intracellular receptor signaling pathway GO:0042752 regulation of circadian rhythm GO:0043153 entrainment of circadian clock by photoperiod GO:0043401 steroid hormone mediated signaling pathway GO:0048511 rhythmic process GO:0048545 response to steroid hormone GO:0050951 sensory perception of temperature stimulus GO:0050961 detection of temperature stimulus involved in sensory perception GO:0050965 detection of temperature stimulus involved in sensory perception of pain 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:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding GO:0001158 enhancer sequence-specific DNA binding GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003707 steroid hormone receptor activity GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding GO:0004887 thyroid hormone receptor activity GO:0035326 enhancer binding GO:0098531 transcription factor activity, direct ligand regulated sequence-specific DNA binding
Cellular Component	-

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

Summary
Symbol	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NR2F6 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	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
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 NR2F6 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	Second most enriched score: 0.57	Sensitive to T cell-mediated killing
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	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
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 NR2F6 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	-0.123	0.736
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.876	0.719
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.422	0.822
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.39	0.392
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.496	0.821
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.252	0.925
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.035	0.923
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.319	0.805
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.269	0.852
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.268	0.813
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	-0.651	0.699
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.19	0.11

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of NR2F6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% 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	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	11.1	11.1	0.36
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	25	25	0.364
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	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NR2F6. 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	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NR2F6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NR2F6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NR2F6. 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	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NR2F6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NR2F6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NR2F6
Name	nuclear receptor subfamily 2, group F, member 6
Aliases	EAR-2; ERBAL2; EAR2; ERBA-related gene-2; V-erbA-related protein 2; nuclear receptor V-erbA-related; v-erb-a ......
Chromosomal Location	19p13.11
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NR2F6 collected from DrugBank database.

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

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