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].

TNF superfamily member 11MIM:602642Ensembl:ENSG00000120659HGNC:HGNC:11926PA3661913q14.11

GO terms in TNFSF11

Term TypeEvidence TypeGO Term IDGO Des.
MFIDAGO:0005125cytokine activity
MFNASGO:0005125cytokine activity
MFNASGO:0005164tumor necrosis factor receptor binding
MFIPIGO:0005515protein binding
MFICGO:0032813tumor necrosis factor receptor superfamily binding
BPIEAGO:0002158osteoclast proliferation
BPIDAGO:0002548monocyte chemotaxis
BPNASGO:0006955immune response
BPIEAGO:0007257activation of JUN kinase activity
BPIEAGO:0010469regulation of signaling receptor activity
BPIDAGO:0019221cytokine-mediated signaling pathway
BPISSGO:0019722calcium-mediated signaling
BPIDAGO:0030316osteoclast differentiation
BPISSGO:0030316osteoclast differentiation
BPNASGO:0030316osteoclast differentiation
BPISSGO:0033209tumor necrosis factor-mediated signaling pathway
BPTASGO:0033209tumor necrosis factor-mediated signaling pathway
BPIEAGO:0033598mammary gland epithelial cell proliferation
BPIDAGO:0034112positive regulation of homotypic cell-cell adhesion
BPIEAGO:0036035osteoclast development
BPIEAGO:0038001paracrine signaling
BPIEAGO:0043123positive regulation of I-kappaB kinase/NF-kappaB signaling
BPIDAGO:0043406positive regulation of MAP kinase activity
BPIEAGO:0044691tooth eruption
BPIEAGO:0045453bone resorption
BPIDAGO:0045672positive regulation of osteoclast differentiation
BPIDAGO:0045780positive regulation of bone resorption
BPIDAGO:0045944positive regulation of transcription by RNA polymerase II
BPIDAGO:0050870positive regulation of T cell activation
BPISSGO:0051091positive regulation of DNA-binding transcription factor activity
BPIDAGO:0051092positive regulation of NF-kappaB transcription factor activity
BPIEAGO:0051260protein homooligomerization
BPISSGO:0051466positive regulation of corticotropin-releasing hormone secretion
BPIEAGO:0051897positive regulation of protein kinase B signaling
BPIEAGO:0055074calcium ion homeostasis
BPIEAGO:0060749mammary gland alveolus development
BPIEAGO:0070371ERK1 and ERK2 cascade
BPISSGO:0071812positive regulation of fever generation by positive regulation of prostaglandin secretion
BPIDAGO:0071847TNFSF11-mediated signaling pathway
BPIDAGO:0071848positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling
BPIDAGO:1902533positive regulation of intracellular signal transduction
BPIEAGO:1990830cellular response to leukemia inhibitory factor
BPIEAGO:2001206positive regulation of osteoclast development
CCNASGO:0005576extracellular region
CCTASGO:0005576extracellular region
CCIEAGO:0005615extracellular space
CCTASGO:0005886plasma membrane
CCNASGO:0005887integral component of plasma membrane

Gene expression in normal tissue: TNFSF11

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in TNFSF11

DatabasePathway IDPathway Des.
reactomeR-HSA-1280215Cytokine Signaling in Immune system
reactomeR-HSA-168256Immune System
reactomeR-HSA-5668541TNFR2 non-canonical NF-kB pathway
reactomeR-HSA-5669034TNFs bind their physiological receptors
reactomeR-HSA-5676594TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
biocartaranklpathwaybone remodeling
pidil6_7pathwayIL6-mediated signaling events
kegghsa04060Cytokine-cytokine receptor interaction - Homo sapiens (human)
kegghsa04064NF-kappa B signaling pathway - Homo sapiens (human)
kegghsa04380Osteoclast differentiation - Homo sapiens (human)
kegghsa04917Prolactin signaling pathway - Homo sapiens (human)
kegghsa05224Breast cancer - Homo sapiens (human)
kegghsa05323Rheumatoid arthritis - Homo sapiens (human)
wikipathwaysWP12Osteoclast Signaling
wikipathwaysWP2018RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway
wikipathwaysWP2848Differentiation Pathway
wikipathwaysWP2877Vitamin D Receptor Pathway
wikipathwaysWP322Osteoblast Signaling

Gene-Drug: Aster Plot

Drug IDDrug NameModel Num.
iGMDRD886Compound 1541A3
iGMDRD84Lovastatin acid3
iGMDRD446LY 21832403
iGMDRD61Kinetin riboside1

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in TNFSF11