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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]
TNFSF11 (TNF Superfamily Member 11) is a Protein Coding gene. Diseases associated with TNFSF11 include Osteopetrosis, Autosomal Recessive 2 and Autosomal Recessive Malignant Osteopetrosis. Among its related pathways are Development_Hedgehog and PTH signaling pathways in bone and cartilage development and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include cytokine activity and tumor necrosis factor receptor superfamily binding. An important paralog of this gene is TNFSF10.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005125 | cytokine activity | IDA,NAS | 9568710 |
GO:0005164 | tumor necrosis factor receptor binding | NAS | 9312132 |
GO:0005515 | protein binding | IPI | 18586671 |
GO:0032813 | tumor necrosis factor receptor superfamily binding | IC | 19940926 |
GO:0042802 | identical protein binding | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | TAS | -- |
GO:0005615 | extracellular space | IEA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
GO:0005887 | integral component of plasma membrane | NAS | 9312132 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | PEDF Induced Signaling |
MIF Mediated Glucocorticoid Regulation
.94
MIF Regulation of Innate Immune Cells
.94
PEDF Induced Signaling
.73
all-trans-Retinoic Acid Signaling in Brain
.71
RAR-Gamma-RXR-Alpha Degradation
.62
|
IL-6 Pathway
.61
STAT3 Pathway
.47
Endothelin-1 Signaling Pathway
.46
|
2 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
|
Molecular Mechanisms of Cancer
.51
|
3 | RANK Signaling in Osteoclasts |
RANK Signaling in Osteoclasts
.45
RANK Pathway
.38
|
|
4 | TNF Superfamily - Human Ligand-Receptor Interactions and their Associated Functions | ||
5 | TNFR1 Pathway |
TRAIL Pathway
.40
|
.34
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001503 | ossification | IEA | -- |
GO:0002158 | osteoclast proliferation | IEA | -- |
GO:0002548 | monocyte chemotaxis | IDA | 15248232 |
GO:0006955 | immune response | NAS | 9312132 |
GO:0007257 | activation of JUN kinase activity | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Lenalidomide | Approved | Pharma | Target, inhibitor, Anti-angiogenic. | Anti-angiogenic. | 911 | |
Denosumab | Approved | Pharma | Target, antibody, antagonist | RANKL antagonist, Osteoclast function modifiers (important in bone metastasis) | 204 | |
Anastrozole | Approved, Investigational | Pharma | Aromatase inhibitor, Potent aromatase (CYP19) inhibitor, Aromatase Inhibitors, Hormone therapy | 337 | ||
Letrozole | Approved, Investigational | Pharma | Non-steroidal aromatase inhibitor, Aromatase Inhibitors | 528 | ||
Thiocolchicoside | Experimental | Pharma | Target, antagonist | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | TNFSF11 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | TNFSF11 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | TNFSF11 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Tnfsf11 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Tnfsf11 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | TNFSF11 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | TNFSF11 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | TNFSF11 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | TNFSF11 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | tnfsf11 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | tnfsf11 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 13 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
716176 | Benign: Autosomal recessive osteopetrosis 2; not provided | 42,600,760(+) | A/G | SYNONYMOUS_VARIANT | |
718598 | Benign: not provided | 42,574,404(+) | C/G | MISSENSE_VARIANT,INTRON_VARIANT | |
719202 | Likely Benign: not provided | 42,600,874(+) | C/T | INTRON_VARIANT | |
724213 | Likely Benign: not provided | 42,606,676(+) | C/T | SYNONYMOUS_VARIANT | |
741128 | Likely Benign: not provided | 42,606,867(+) | G/A | SYNONYMOUS_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
osteopetrosis, autosomal recessive 2 |
|
|
autosomal recessive malignant osteopetrosis |
|
|
osteopetrosis |
|
|
periapical granuloma |
|
|
multicentric carpotarsal osteolysis syndrome |
|