TISIDB

Summary
Symbol	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
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	Secreted.
Domain	PF00531 Death domain PF00020 TNFR/NGFR cysteine-rich region
Function	Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.

> Gene Ontology [ TOP ]
Biological Process	GO:0001501 skeletal system development GO:0001894 tissue homeostasis GO:0002237 response to molecule of bacterial origin GO:0007584 response to nutrient GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0030198 extracellular matrix organization GO:0031667 response to nutrient levels GO:0032026 response to magnesium ion GO:0032496 response to lipopolysaccharide GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034103 regulation of tissue remodeling GO:0034104 negative regulation of tissue remodeling GO:0034612 response to tumor necrosis factor GO:0042475 odontogenesis of dentin-containing tooth GO:0042476 odontogenesis GO:0042481 regulation of odontogenesis GO:0042483 negative regulation of odontogenesis GO:0042487 regulation of odontogenesis of dentin-containing tooth GO:0042489 negative regulation of odontogenesis of dentin-containing tooth GO:0042493 response to drug GO:0043062 extracellular structure organization GO:0043410 positive regulation of MAPK cascade GO:0043627 response to estrogen GO:0045124 regulation of bone resorption GO:0045453 bone resorption GO:0045779 negative regulation of bone resorption GO:0046685 response to arsenic-containing substance GO:0046849 bone remodeling GO:0046850 regulation of bone remodeling GO:0046851 negative regulation of bone remodeling GO:0048771 tissue remodeling GO:0048871 multicellular organismal homeostasis GO:0060249 anatomical structure homeostasis GO:0071356 cellular response to tumor necrosis factor GO:2000027 regulation of organ morphogenesis
Molecular Function	GO:0005031 tumor necrosis factor-activated receptor activity GO:0005035 death receptor activity GO:0005125 cytokine activity
Cellular Component	GO:0005578 proteinaceous extracellular matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04380 Osteoclast differentiation
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-5668541: TNFR2 non-canonical NF-kB pathway R-HSA-5669034: TNFs bind their physiological receptors

Summary
Symbol	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TNFRSF11B 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 TNFRSF11B and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27530322	Glioblastoma	Inhibit immunity (T cell function)	CCL2 Produced by the Glioma Microenvironment Is Essential for the Recruitment of Regulatory T Cells and Myeloid-Derived Suppressor Cells. In many aggressive cancers, such as glioblastoma multiforme, progression is enabled by local immunosuppression driven by the accumulation of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). Here we report that macrophages and microglia within the glioma microenvironment produce CCL2, a chemokine that is critical for recruiting both CCR4+?Treg and CCR2+Ly-6C+?monocytic MDSCs in this disease setting. In murine gliomas, we established novel roles for tumor-derived CCL20 and osteoprotegerin in inducing CCL2 production from macrophages and microglia.

Summary
Symbol	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
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 TNFRSF11B 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	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
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 TNFRSF11B 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	0.04	0.935
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.543	0.501
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.459	0.518
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1.054	0.0741
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.505	0.685
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.76	0.314
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.398	0.54
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.312	0.757
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.515	0.629
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.129	0.951
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	0.168	0.953
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.674	0.00468

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TNFRSF11B 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	6.8	-3.1	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	8.5	-4.8	0.66
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
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	7.7	9.1	-1.4	1
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	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	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	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TNFRSF11B. 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	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TNFRSF11B. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TNFRSF11B. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TNFRSF11B. 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	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TNFRSF11B expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TNFRSF11B and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TNFRSF11B
Name	tumor necrosis factor receptor superfamily, member 11b
Aliases	osteoprotegerin; osteoclastogenesis inhibitory factor; Tumor necrosis factor receptor superfamily member 11B
Chromosomal Location	8q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TNFRSF11B collected from DrugBank database.

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

Browse TNFRSF11B