TNFSF11
Summary: This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| TNF superfamily member 11 | MIM:602642 | Ensembl:ENSG00000120659 | HGNC:HGNC:11926 | PA36619 | 13q14.11 |
GO terms in TNFSF11
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IDA | GO:0005125 | cytokine activity |
| MF | NAS | GO:0005125 | cytokine activity |
| MF | NAS | GO:0005164 | tumor necrosis factor receptor binding |
| MF | IPI | GO:0005515 | protein binding |
| MF | IC | GO:0032813 | tumor necrosis factor receptor superfamily binding |
| BP | IEA | GO:0001503 | ossification |
| BP | IEA | GO:0002158 | osteoclast proliferation |
| BP | IDA | GO:0002548 | monocyte chemotaxis |
| BP | NAS | GO:0006955 | immune response |
| BP | IEA | GO:0007257 | activation of JUN kinase activity |
| BP | IEA | GO:0010469 | regulation of signaling receptor activity |
| BP | IDA | GO:0019221 | cytokine-mediated signaling pathway |
| BP | ISS | GO:0019722 | calcium-mediated signaling |
| BP | IDA | GO:0030316 | osteoclast differentiation |
| BP | ISS | GO:0030316 | osteoclast differentiation |
| BP | NAS | GO:0030316 | osteoclast differentiation |
| BP | ISS | GO:0033209 | tumor necrosis factor-mediated signaling pathway |
| BP | TAS | GO:0033209 | tumor necrosis factor-mediated signaling pathway |
| BP | IEA | GO:0033598 | mammary gland epithelial cell proliferation |
| BP | IDA | GO:0034112 | positive regulation of homotypic cell-cell adhesion |
| BP | IEA | GO:0036035 | osteoclast development |
| BP | IEA | GO:0038001 | paracrine signaling |
| BP | IEA | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | IDA | GO:0043406 | positive regulation of MAP kinase activity |
| BP | IEA | GO:0044691 | tooth eruption |
| BP | IEA | GO:0045453 | bone resorption |
| BP | IDA | GO:0045672 | positive regulation of osteoclast differentiation |
| BP | IDA | GO:0045780 | positive regulation of bone resorption |
| BP | IDA | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| BP | IDA | GO:0050870 | positive regulation of T cell activation |
| BP | ISS | GO:0051091 | positive regulation of DNA-binding transcription factor activity |
| BP | IDA | GO:0051092 | positive regulation of NF-kappaB transcription factor activity |
| BP | IEA | GO:0051260 | protein homooligomerization |
| BP | ISS | GO:0051466 | positive regulation of corticotropin-releasing hormone secretion |
| BP | IEA | GO:0051897 | positive regulation of protein kinase B signaling |
| BP | IEA | GO:0055074 | calcium ion homeostasis |
| BP | IEA | GO:0060749 | mammary gland alveolus development |
| BP | IEA | GO:0070371 | ERK1 and ERK2 cascade |
| BP | ISS | GO:0071812 | positive regulation of fever generation by positive regulation of prostaglandin secretion |
| BP | IDA | GO:0071847 | TNFSF11-mediated signaling pathway |
| BP | IDA | GO:0071848 | positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling |
| BP | IDA | GO:1902533 | positive regulation of intracellular signal transduction |
| BP | IEA | GO:1990830 | cellular response to leukemia inhibitory factor |
| BP | IEA | GO:2001206 | positive regulation of osteoclast development |
| CC | NAS | GO:0005576 | extracellular region |
| CC | TAS | GO:0005576 | extracellular region |
| CC | IEA | GO:0005615 | extracellular space |
| CC | IEA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005886 | plasma membrane |
| CC | NAS | GO:0005887 | integral component of plasma membrane |
Gene expression in normal tissue: TNFSF11
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in TNFSF11
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway |
| reactome | R-HSA-5669034 | TNFs bind their physiological receptors |
| reactome | R-HSA-5676594 | TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway |
| biocarta | ranklpathway | bone remodeling |
| pid | il6_7pathway | IL6-mediated signaling events |
| kegg | hsa04060 | Cytokine-cytokine receptor interaction - Homo sapiens (human) |
| kegg | hsa04064 | NF-kappa B signaling pathway - Homo sapiens (human) |
| kegg | hsa04380 | Osteoclast differentiation - Homo sapiens (human) |
| kegg | hsa04917 | Prolactin signaling pathway - Homo sapiens (human) |
| kegg | hsa05224 | Breast cancer - Homo sapiens (human) |
| kegg | hsa05323 | Rheumatoid arthritis - Homo sapiens (human) |
| wikipathways | WP12 | Osteoclast Signaling |
| wikipathways | WP2018 | RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway |
| wikipathways | WP2848 | Differentiation Pathway |
| wikipathways | WP2877 | Vitamin D Receptor Pathway |
| wikipathways | WP322 | Osteoblast Signaling |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD705 | Nakiterpiosin | 3 |
| iGMDRD6 | AM-580 | 3 |
| iGMDRD481 | Dactolisib | 1 |
| iGMDRD121 | GMX1778 | 3 |
| iGMDRD64 | Parbendazole | 3 |
| iGMDRD886 | Compound 1541A | 3 |
| iGMDRD505 | Pevonedistat | 3 |
| iGMDRD116 | CD437 | 3 |
| iGMDRD79 | Gemcitabine | 3 |
| iGMDRD151 | CHM-1 | 3 |
| iGMDRD554 | CHEMBL1434137 | 1 |
| iGMDRD84 | Lovastatin acid | 3 |
| iGMDRD1008 | SR-II-138A | 3 |
| iGMDRD123 | Isoevodiamine | 3 |
| iGMDRD446 | LY 2183240 | 3 |
| iGMDRD152 | 179324-69-7 | 5 |
| iGMDRD61 | Kinetin riboside | 1 |
| iGMDRD193 | Fqi1 | 3 |
| iGMDRD237 | ABT-751 | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in TNFSF11
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