TISIDB

Summary
Symbol	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
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	PF16179 Rel homology dimerisation domain PF00554 Rel homology DNA-binding domain
Function	Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.

> Gene Ontology [ TOP ]
Biological Process	GO:0001818 negative regulation of cytokine production GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0032479 regulation of type I interferon production GO:0032480 negative regulation of type I interferon production GO:0032606 type I interferon production GO:0032608 interferon-beta production GO:0032648 regulation of interferon-beta production GO:0032688 negative regulation of interferon-beta production GO:0038061 NIK/NF-kappaB signaling GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0070997 neuron death GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death
Molecular Function	GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding GO:0001158 enhancer sequence-specific DNA binding GO:0001205 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003682 chromatin binding GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0035326 enhancer binding
Cellular Component	GO:0005667 transcription factor complex GO:0033256 I-kappaB/NF-kappaB complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04014 Ras signaling pathway
Reactome	R-HSA-1169091: Activation of NF-kappaB in B cells R-HSA-1280218: Adaptive Immune System R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR) R-HSA-168256: Immune System R-HSA-983705: Signaling by the B Cell Receptor (BCR)

Summary
Symbol	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between REL 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 REL and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28886380	Melanoma	Inhibit immunity; Resistant to immunotherapy	We show that NF-κB c-Rel ablation specifically impairs the generation and maintenance of the activated Treg (aTreg) subset, which is known to be enriched at sites of tumors. Moreover, chemical inhibition of c-Rel function delayed melanoma growth by impairing a Treg-mediated immunosuppression and potentiated the effects of anti-PD-1 immunotherapy.

Summary
Symbol	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
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 REL 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	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
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 REL 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	0.288	0.384
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.543	0.477
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.099	0.879
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.559	0.108
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.946	0.648
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.075	0.976
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.376	0.185
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.409	0.616
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.342	0.705
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.81	0.181
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	1.487	0.059
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.192	0.0827

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of REL 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	2.7	1	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	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	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	2.6	0	2.6	1
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	6.2	0	6.2	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	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of REL. 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	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of REL. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by REL. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of REL. 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	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of REL expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between REL and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	REL
Name	v-rel avian reticuloendotheliosis viral oncogene homolog
Aliases	c-Rel; oncogene REL, avian reticuloendotheliosis; Proto-oncogene c-Rel
Chromosomal Location	2p13-p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting REL collected from DrugBank database.

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

Browse REL