TNFSF11
TNF Superfamily Member 11 (RANKL) – Key Regulator of Bone Remodeling and Immune Function
Gene Information Card
| Symbol | TNFSF11 |
|---|---|
| Full Name | TNF Superfamily Member 11 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q14.11 |
| NCBI Gene ID | 8600 ncbi.nlm.nih.gov/gene/8600 |
| Ensembl ID | ENSG00000120659 |
| UniProt ID | O14788 |
| OMIM ID | 602642 |
| HGNC ID | 11926 |
| Aliases | RANKL, OPGL, TRANCE, ODF, CD254, sOdf |
Description
TNFSF11 encodes RANKL (Receptor Activator of Nuclear Factor-κB Ligand), a member of the tumor necrosis factor (TNF) superfamily. RANKL is a transmembrane protein essential for osteoclast differentiation, activation, and survival. It binds to its receptor RANK (TNFRSF11A) on osteoclast precursors, triggering NF-κB and MAPK signaling pathways. RANKL also plays roles in immune regulation, lymph node development, and mammary gland formation. Alternative splicing produces soluble and membrane-bound isoforms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteopetrosis, autosomal recessive 2 (OPTB2) | Loss-of-function mutations in TNFSF11 impair RANKL-mediated osteoclastogenesis, leading to dense but brittle bones due to defective bone resorption. | ClinVar, OMIM #612301 |
| Paget disease of bone (PDB) | Gain-of-function or overexpression of RANKL enhances osteoclast activity, causing abnormal bone remodeling, pain, and deformities. | OMIM #602642, NCBI Gene |
| Osteoporosis | Increased RANKL/OPG ratio promotes excessive bone resorption, contributing to reduced bone mineral density and fracture risk. | ClinVar, literature |
| RANKL deficiency | Homozygous loss-of-function mutations cause severe osteopetrosis with lack of osteoclasts, often fatal in infancy. | OMIM #612301 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 0.0 | Not detected |
| Lymph node | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Thymus | 0.0 | Not detected |
| Tonsil | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 0.0 | Not expressed |
| HeLa | 0.0 | Not expressed |
| K562 | 0.0 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.525C>A (p.Tyr175Ter) | Nonsense | Rare | Loss of function; truncation of RANKL protein |
| c.686G>A (p.Arg229Gln) | Missense | Rare | Loss of function; impaired receptor binding |
| c.827T>C (p.Leu276Pro) | Missense | Rare | Loss of function; disrupts protein folding |
| c.940C>T (p.Arg314Trp) | Missense | Rare | Loss of function; reduced secretion |
Mutation functional classification
Loss of Function (LOF)
Mutations that truncate or destabilize RANKL, impairing osteoclast differentiation and causing osteopetrosis.
Gain of Function (GOF)
Not well documented; overexpression or activating mutations may contribute to Paget disease or osteoporosis.
Dominant Negative (DN)
Not reported for TNFSF11.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005125 – cytokine activity | • GO:0005164 – tumor necrosis factor receptor binding |
| • GO:0005515 – protein binding | • GO:0030154 – cell differentiation |
| • GO:0043531 – ADP binding | • GO:0046872 – metal ion binding |
Pathways
• RANKL/RANK signaling pathway (Reactome: R-HSA-5663205)
• Osteoclast differentiation (KEGG: hsa04380)
• NF-κB signaling pathway (KEGG: hsa04064)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
RANKL (O14788) is a 317-amino acid type II transmembrane protein with an extracellular TNF homology domain. It exists as a membrane-bound homotrimer or a soluble form generated by proteolytic cleavage. RANKL binds to RANK (TNFRSF11A) and the decoy receptor OPG (TNFRSF11B). It is essential for osteoclastogenesis, lymph node organogenesis, and mammary gland development. Dysregulation leads to bone diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFSF11 Knockout HEK293 Cell Line | EDC07596 | Human | 8600 | Details Get a Quote |
| TNFSF11 Knockout MLO-Y4 Cell Line | EDJ-KZ54 | Mouse | 8600 | Details Get a Quote |
| TNFSF11 Knockout HeLa Cell Line | EDJ-KQ54949 | Human | 8600 | Details Get a Quote |
| TNFSF11 Knockout A-549 Cell Line | EDJ-KQ63435 | Human | 8600 | Details Get a Quote |
| TNFSF11 Knockout HCT 116 Cell Line | EDJ-KQ71901 | Human | 8600 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
