Browse TNFSF11

Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
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
 
Subcellular Location Isoform 1: Cell membrane; Single-pass type II membrane protein.; SUBCELLULAR LOCATION: Isoform 3: Cell membrane; Single-pass type II membrane protein.; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm ; SUBCELLULAR LOCATION: Tumor necrosis factor ligand superfamily member 11, soluble form: Secreted
Domain PF00229 TNF(Tumour Necrosis Factor) family
Function

Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy (PubMed:22664871). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (By similarity).

> Gene Ontology
 
Biological Process GO:0000187 activation of MAPK activity
GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001659 temperature homeostasis
GO:0001660 fever generation
GO:0001894 tissue homeostasis
GO:0002158 osteoclast proliferation
GO:0002521 leukocyte differentiation
GO:0002526 acute inflammatory response
GO:0002548 monocyte chemotaxis
GO:0002573 myeloid leukocyte differentiation
GO:0002673 regulation of acute inflammatory response
GO:0002675 positive regulation of acute inflammatory response
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002761 regulation of myeloid leukocyte differentiation
GO:0002763 positive regulation of myeloid leukocyte differentiation
GO:0002790 peptide secretion
GO:0002791 regulation of peptide secretion
GO:0002793 positive regulation of peptide secretion
GO:0006820 anion transport
GO:0006869 lipid transport
GO:0006953 acute-phase response
GO:0007159 leukocyte cell-cell adhesion
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007254 JNK cascade
GO:0007257 activation of JUN kinase activity
GO:0009914 hormone transport
GO:0010720 positive regulation of cell development
GO:0010817 regulation of hormone levels
GO:0010876 lipid localization
GO:0015711 organic anion transport
GO:0015718 monocarboxylic acid transport
GO:0015732 prostaglandin transport
GO:0015833 peptide transport
GO:0015908 fatty acid transport
GO:0019722 calcium-mediated signaling
GO:0019932 second-messenger-mediated signaling
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0023061 signal release
GO:0030072 peptide hormone secretion
GO:0030099 myeloid cell differentiation
GO:0030316 osteoclast differentiation
GO:0030595 leukocyte chemotaxis
GO:0030879 mammary gland development
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031349 positive regulation of defense response
GO:0031620 regulation of fever generation
GO:0031622 positive regulation of fever generation
GO:0031649 heat generation
GO:0031650 regulation of heat generation
GO:0031652 positive regulation of heat generation
GO:0032103 positive regulation of response to external stimulus
GO:0032147 activation of protein kinase activity
GO:0032303 regulation of icosanoid secretion
GO:0032305 positive regulation of icosanoid secretion
GO:0032306 regulation of prostaglandin secretion
GO:0032308 positive regulation of prostaglandin secretion
GO:0032309 icosanoid secretion
GO:0032310 prostaglandin secretion
GO:0032368 regulation of lipid transport
GO:0032370 positive regulation of lipid transport
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0033598 mammary gland epithelial cell proliferation
GO:0033674 positive regulation of kinase activity
GO:0034103 regulation of tissue remodeling
GO:0034105 positive regulation of tissue remodeling
GO:0034109 homotypic cell-cell adhesion
GO:0034110 regulation of homotypic cell-cell adhesion
GO:0034112 positive regulation of homotypic cell-cell adhesion
GO:0034612 response to tumor necrosis factor
GO:0036035 osteoclast development
GO:0038001 paracrine signaling
GO:0042110 T cell activation
GO:0042886 amide transport
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043270 positive regulation of ion transport
GO:0043396 corticotropin-releasing hormone secretion
GO:0043397 regulation of corticotropin-releasing hormone secretion
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043491 protein kinase B signaling
GO:0043506 regulation of JUN kinase activity
GO:0043507 positive regulation of JUN kinase activity
GO:0044070 regulation of anion transport
GO:0045124 regulation of bone resorption
GO:0045453 bone resorption
GO:0045637 regulation of myeloid cell differentiation
GO:0045639 positive regulation of myeloid cell differentiation
GO:0045670 regulation of osteoclast differentiation
GO:0045672 positive regulation of osteoclast differentiation
GO:0045780 positive regulation of bone resorption
GO:0045785 positive regulation of cell adhesion
GO:0045860 positive regulation of protein kinase activity
GO:0046328 regulation of JNK cascade
GO:0046330 positive regulation of JNK cascade
GO:0046849 bone remodeling
GO:0046850 regulation of bone remodeling
GO:0046852 positive regulation of bone remodeling
GO:0046879 hormone secretion
GO:0046883 regulation of hormone secretion
GO:0046887 positive regulation of hormone secretion
GO:0046942 carboxylic acid transport
GO:0048732 gland development
GO:0048771 tissue remodeling
GO:0048871 multicellular organismal homeostasis
GO:0050673 epithelial cell proliferation
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050900 leukocyte migration
GO:0051047 positive regulation of secretion
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051259 protein oligomerization
GO:0051260 protein homooligomerization
GO:0051403 stress-activated MAPK cascade
GO:0051466 positive regulation of corticotropin-releasing hormone secretion
GO:0051896 regulation of protein kinase B signaling
GO:0051897 positive regulation of protein kinase B signaling
GO:0055074 calcium ion homeostasis
GO:0060249 anatomical structure homeostasis
GO:0060326 cell chemotaxis
GO:0060348 bone development
GO:0060749 mammary gland alveolus development
GO:0061180 mammary gland epithelium development
GO:0061377 mammary gland lobule development
GO:0061515 myeloid cell development
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0071356 cellular response to tumor necrosis factor
GO:0071593 lymphocyte aggregation
GO:0071674 mononuclear cell migration
GO:0071715 icosanoid transport
GO:0071812 positive regulation of fever generation by positive regulation of prostaglandin secretion
GO:0071847 TNFSF11-mediated signaling pathway
GO:0071848 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0072507 divalent inorganic cation homeostasis
GO:0090087 regulation of peptide transport
GO:0090276 regulation of peptide hormone secretion
GO:0090277 positive regulation of peptide hormone secretion
GO:0097529 myeloid leukocyte migration
GO:0098751 bone cell development
GO:1902105 regulation of leukocyte differentiation
GO:1902107 positive regulation of leukocyte differentiation
GO:1903010 regulation of bone development
GO:1903012 positive regulation of bone development
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903532 positive regulation of secretion by cell
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1903793 positive regulation of anion transport
GO:2000191 regulation of fatty acid transport
GO:2000193 positive regulation of fatty acid transport
GO:2001204 regulation of osteoclast development
GO:2001206 positive regulation of osteoclast development
Molecular Function GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005164 tumor necrosis factor receptor binding
GO:0032813 tumor necrosis factor receptor superfamily binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04064 NF-kappa B signaling pathway
hsa04380 Osteoclast differentiation
hsa04917 Prolactin signaling pathway
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-5676594: TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-5668541: TNFR2 non-canonical NF-kB pathway
R-HSA-5669034: TNFs bind their physiological receptors
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TNFSF11 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
 
  Literatures describing the relation between TNFSF11 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24752296MelanomaInhibit immunityWe show that in vivo RANKL blockade selectively and transiently depletes Aire and TSA expression in the thymus to create a window of defective negative selection. Furthermore, we demonstrate that RANKL blockade can rescue melanoma-specific T cells from thymic deletion and that persistence of these tumor-specific effector T cells promoted increased host survival in response to tumor challenge.
28634284MelanomaInhibit immunity; Immunotherapy targetCo-administration of RANKL and CTLA4 Antibodies Enhances Lymphocyte-Mediated Antitumor Immunity in Mice. RANKL blockade improved the efficacy of anti-CTLA4 mAbs against solid tumors and experimental metastases, with regulatory T-cell (Treg)-depleting anti-CTLA4 mAbs of the mouse IgG2a isotype showing greatest combinatorial activity.
29872559Melanoma; Prostate Carcinoma; Colon CarcinomaInhibit immunity; Resistant to immunotherapyRANKL blockade improves efficacy of PD1-PD-L1 blockade or dual PD1-PD-L1 and CTLA4 blockade in mouse models of cancer. Furthermore, addition of anti-RANKL to anti-PD1 and anti-CTLA4 resulted in superior anti-tumor responses, irrespective of the ability of anti-CTLA4 isotype to engage activating FcR, and concurrent or delayed RANKL blockade was most effective. Early-during-treatment assessment reveals this triple combination therapy compared to dual anti-PD1 and anti-CTLA4 combination therapy further increased the proportion of tumor-infiltrating CD4+ and CD8+ T cells that can produce both IFN-γ and TNF. Finally, RANKL expression appears to identify tumor-specific CD8+ T cells expressing higher levels of PD1 which can be modulated by anti-PD1.
16880256Multiple myeloma(IgA, IgD, IgE, IgM, IgG)Inhibit immunityIn this study, we show that the clonogenicity of several human tumor cell lines and primary tumor cells from myeloma patients is enhanced by their interactions with DCs. Myeloma cells cultured in the presence of DCs have an altered phenotype with an increased proportion of cells lacking terminal plasma cell differentiation marker CD138. DC-tumor interaction also leads to the up-regulation of B cell lymphoma 6 expression in myeloma cells. Effects of DCs on myeloma cells are inhibited by blockade of the receptor activator of NF-kB (RANK)-RANK ligand and B cell-activating factor-APRIL (a proliferation-inducing ligand)-mediated interactions.
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
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
  Statistical results of TNFSF11 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
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
 
Points in the above scatter plot represent the expression difference of TNFSF11 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.4990.364
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.8160.345
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2860.704
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-1.5930.0274
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-2.5770.0212
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3510.793
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2630.731
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0550.96
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.7880.52
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0880.894
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.5810.509
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.6490.0144
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TNFSF11 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275903.4-3.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TNFSF11. 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
 
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TNFSF11. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TNFSF11.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TNFSF11. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TNFSF11 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TNFSF11 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTNFSF11
Nametumor necrosis factor (ligand) superfamily, member 11
Aliases TRANCE; RANKL; OPGL; CD254; OPTB2; hRANKL2; TNF-related activation-induced cytokine; osteoclast differentiat ......
Chromosomal Location13q14
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TNFSF11 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting TNFSF11.
ID Name Drug Type Targets #Targets
DB00480LenalidomideSmall MoleculeCDH5, CRBN, PTGS2, TNFSF114
DB06643DenosumabBiotechTNFSF111
DB11582ThiocolchicosideSmall MoleculeGABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GA ......18