======= TNFSF11 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TNFSF11
  * **<color #00a2e8>Official Name</color>**: TNF superfamily member 11
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=8600|8600]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O14788|O14788]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TNFSF11&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TNFSF11|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602642|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000250|UniProtKB:O35235, ECO:0000269|PubMed:22664871}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|TNF|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of fever generation by positive regulation of prostaglandin secretion|
|positive regulation of corticotropin-releasing hormone secretion|
|positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling|
|regulation of corticotropin-releasing hormone secretion|
|regulation of actin binding|
|positive regulation of osteoclast development|
|osteoclast proliferation|
|TNFSF11-mediated signaling pathway|
|tumor necrosis factor receptor superfamily binding|
|positive regulation of homotypic cell-cell adhesion|
|tooth eruption|
|paracrine signaling|
|positive regulation of fever generation|
|positive regulation of bone development|
|osteoclast development|
|regulation of fever generation|
|positive regulation of prostaglandin secretion|
|positive regulation of heat generation|
|regulation of prostaglandin secretion|
|regulation of osteoclast development|
|mammary gland epithelial cell proliferation|
|regulation of heat generation|
|positive regulation of icosanoid secretion|
|mammary gland alveolus development|
|positive regulation of fatty acid transport|
|positive regulation of bone remodeling|
|positive regulation of bone resorption|
|mammary gland lobule development|
|regulation of icosanoid secretion|
|regulation of bone development|
|bone resorption|
|bone cell development|
|regulation of homotypic cell-cell adhesion|
|positive regulation of osteoclast differentiation|
|regulation of fatty acid transport|
|ERK1 and ERK2 cascade|
|positive regulation of acute inflammatory response|
|tumor necrosis factor receptor binding|
|positive regulation of tissue remodeling|
|positive regulation of organic acid transport|
|positive regulation of neurotransmitter transport|
|activation of JUN kinase activity|
|regulation of bone resorption|
|monocyte chemotaxis|
|regulation of acute inflammatory response|
|osteoclast differentiation|
|bone remodeling|
|mononuclear cell migration|
|regulation of bone remodeling|
|positive regulation of anion transport|
|positive regulation of myeloid leukocyte differentiation|
|regulation of organic acid transport|
|mammary gland epithelium development|
|myeloid cell development|
|positive regulation of lipid transport|
|regulation of osteoclast differentiation|
|positive regulation of JUN kinase activity|
|regulation of tissue remodeling|
|positive regulation of lipid localization|
|JNK cascade|
|regulation of JUN kinase activity|
|epithelial cell proliferation|
|positive regulation of myeloid cell differentiation|
|regulation of anion transport|
|cellular response to leukemia inhibitory factor|
|response to leukemia inhibitory factor|
|positive regulation of peptide hormone secretion|
|leukocyte proliferation|
|tissue remodeling|
|stress-activated MAPK cascade|
|regulation of lipid transport|
|myeloid leukocyte differentiation|
|regulation of myeloid leukocyte differentiation|
|tumor necrosis factor-mediated signaling pathway|
|odontogenesis|
|mammary gland development|
|positive regulation of hormone secretion|
|myeloid leukocyte migration|
|regulation of lipid localization|
|positive regulation of JNK cascade|
|positive regulation of inflammatory response|
|stress-activated protein kinase signaling cascade|
|regulation of neurotransmitter transport|
|leukocyte chemotaxis|
|calcium-mediated signaling|
|positive regulation of leukocyte differentiation|
|positive regulation of NF-kappaB transcription factor activity|
|activation of MAPK activity|
|positive regulation of protein kinase B signaling|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|cytokine activity|
|positive regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of JNK cascade|
|positive regulation of hemopoiesis|
|tissue homeostasis|
|bone development|
|positive regulation of T cell activation|
|regulation of peptide hormone secretion|
|cell chemotaxis|
|positive regulation of ERK1 and ERK2 cascade|
|positive regulation of leukocyte cell-cell adhesion|
|regulation of protein binding|
|regulation of protein kinase B signaling|
|myeloid cell differentiation|
|regulation of myeloid cell differentiation|
|regulation of stress-activated MAPK cascade|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of stress-activated protein kinase signaling cascade|
|cellular response to tumor necrosis factor|
|positive regulation of cell-cell adhesion|
|positive regulation of MAP kinase activity|
|positive regulation of DNA-binding transcription factor activity|
|ossification|
|response to tumor necrosis factor|
|regulation of hormone secretion|
|regulation of leukocyte differentiation|
|positive regulation of ion transport|
|positive regulation of peptide secretion|
|regulation of ERK1 and ERK2 cascade|
|regulation of leukocyte cell-cell adhesion|
|regulation of T cell activation|
|multicellular organismal homeostasis|
|activation of protein kinase activity|
|leukocyte differentiation|
|second-messenger-mediated signaling|
|regulation of inflammatory response|
|positive regulation of protein serine/threonine kinase activity|
|protein homooligomerization|
|anatomical structure homeostasis|
|regulation of MAP kinase activity|
|positive regulation of lymphocyte activation|
|MAPK cascade|
|regulation of binding|
|leukocyte migration|
|signal transduction by protein phosphorylation|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of secretion by cell|
|positive regulation of leukocyte activation|
|gland development|
|positive regulation of cell activation|
|regulation of DNA-binding transcription factor activity|
|positive regulation of secretion|
|calcium ion homeostasis|
|regulation of hemopoiesis|
|positive regulation of defense response|
|divalent inorganic cation homeostasis|
|regulation of peptide secretion|
|skeletal system development|
|regulation of lymphocyte activation|
|regulation of protein serine/threonine kinase activity|
|protein complex oligomerization|
|positive regulation of protein kinase activity|
|regulation of hormone levels|
|positive regulation of cell development|
|positive regulation of MAPK cascade|
|chemotaxis|
|taxis|
|cell population proliferation|
|hemopoiesis|
|positive regulation of kinase activity|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|hematopoietic or lymphoid organ development|
|metal ion homeostasis|
|regulation of cell activation|
|immune system development|
|positive regulation of transferase activity|
|cytokine-mediated signaling pathway|
|regulation of cell adhesion|
|regulation of ion transport|
|cation homeostasis|
|inorganic ion homeostasis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|ion homeostasis|
|regulation of protein kinase activity|
|regulation of secretion|
|regulation of kinase activity|
|regulation of cell development|
|animal organ morphogenesis|
|cell migration|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|positive regulation of transport|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|positive regulation of phosphorylation|
|cell motility|
|localization of cell|
|regulation of response to external stimulus|
|response to cytokine|
|chemical homeostasis|
|epithelium development|
|cell-cell signaling|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|positive regulation of immune system process|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|phosphorylation|
|locomotion|
|positive regulation of developmental process|
|integral component of plasma membrane|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of response to stress|
|positive regulation of transcription, DNA-templated|
|movement of cell or subcellular component|
|protein-containing complex assembly|
|regulation of phosphorylation|
|extracellular space|
|positive regulation of cellular protein metabolic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp317|Geldanamycin 0.015 to 0.05μM on day4 R07 exp317]]|-2.05|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 8820
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -2.56 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TNFSF11 Expression in NALM6 Cells: -2.56'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>