TNFRSF11A Gene: RANK Receptor in Bone and Immune Regulation
Key mediator of NF-κB signaling in osteoclastogenesis, immune responses, and cancer
Gene Information Card
| Symbol | TNFRSF11A |
|---|---|
| Full Name | TNF receptor superfamily member 11a |
| Gene Type | protein-coding |
| Chromosomal Location | 18q21.33 |
| NCBI Gene ID | 8792 ncbi.nlm.nih.gov/gene/8792 |
| Ensembl ID | ENSG00000141655 |
| UniProt ID | Q9Y6Q6 |
| OMIM ID | 603499 |
| HGNC ID | 11908 |
| Aliases | RANK, CD265, FEO, LOH18CR1, OSTS, PDB2, RANK (receptor activator of NF-κB) |
Description
TNFRSF11A encodes the receptor activator of NF-κB (RANK), a type I transmembrane protein of the tumor necrosis factor receptor superfamily. RANK is the receptor for RANKL (TNFSF11) and is essential for osteoclast differentiation, activation, and survival. It also plays roles in immune regulation, lymph node development, and mammary gland formation. Mutations in TNFRSF11A are associated with familial expansile osteolysis, Paget disease of bone, and osteopetrosis. The gene is also implicated in cancer progression, particularly in bone metastases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial expansile osteolysis (FEO) | Activating mutations in the signal peptide region lead to constitutive RANK signaling, increasing osteoclast activity. | OMIM #174810; PMID: 10677303 |
| Paget disease of bone (PDB2) | Missense mutations (e.g., p.Val192Met) in the extracellular domain enhance RANKL-independent signaling, causing abnormal bone remodeling. | OMIM #602080; PMID: 11544505 |
| Osteopetrosis, autosomal recessive 7 | Loss-of-function mutations impair RANK signaling, leading to defective osteoclast formation and increased bone density. | OMIM #612301; PMID: 17554309 |
| Breast cancer (bone metastasis) | RANK overexpression in tumor cells promotes migration and bone invasion via RANKL-RANK signaling. | COSMIC; PMID: 20844536 |
| Multiple myeloma | RANKL produced by myeloma cells activates RANK on osteoclast precursors, driving lytic bone lesions. | PMID: 12663457 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | Not available | High expression in osteoclast precursors |
| Lymph node | Not available | Expressed in dendritic cells and T cells |
| Mammary gland | Not available | Expressed during lactation |
| Thymus | Not available | Moderate expression |
| Spleen | Not available | Moderate expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoclast precursors (RAW264.7) | Not available | High expression; essential for RANKL-induced differentiation |
| Dendritic cells (monocyte-derived) | Not available | Expressed; involved in immune activation |
| Breast cancer cell lines (MDA-MB-231) | Not available | Overexpressed; promotes invasiveness |
| Multiple myeloma cell lines (RPMI-8226) | Not available | Expressed; contributes to bone disease |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.675dupC (p.Val226fs) | Frameshift | Rare | Loss of function; associated with osteopetrosis |
| c.575C>T (p.Pro192Leu) | Missense | Rare | Gain of function; associated with Paget disease |
| c.376C>T (p.Arg126Cys) | Missense | Rare | Gain of function; associated with familial expansile osteolysis |
| c.146A>G (p.Asn49Ser) | Missense | Rare | Gain of function; associated with Paget disease |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift or nonsense) impair RANK signaling, leading to osteoclast-poor osteopetrosis due to defective osteoclast differentiation.
Gain of Function (GOF)
Gain-of-function mutations (e.g., missense in signal peptide or extracellular domain) cause constitutive RANK activation, increasing osteoclast activity and leading to Paget disease or familial expansile osteolysis.
Dominant Negative (DN)
Dominant-negative effects are not well documented for TNFRSF11A; most pathogenic mutations are either loss-of-function (recessive) or gain-of-function (dominant).
View complete mutation data：
Gene Ontology (GO)
| • receptor activity (GO:0004872) | • tumor necrosis factor-activated receptor activity (GO:0005031) |
| • protein binding (GO:0005515) | • signal transduction (GO:0007165) |
| • NF-kappaB transcription factor activity (GO:0004890) | • positive regulation of osteoclast differentiation (GO:0045672) |
| • immune response (GO:0006955) | • apoptotic process (GO:0006915) |
Pathways
• RANKL/RANK signaling pathway (KEGG: hsa04380)
• Osteoclast differentiation (KEGG: hsa04380)
• NF-kappaB signaling pathway (KEGG: hsa04064)
• TNF signaling pathway (KEGG: hsa04668)
Protein Summary
The RANK protein (UniProt Q9Y6Q6) is a 616-amino-acid type I membrane protein with an N-terminal extracellular domain containing cysteine-rich repeats, a single transmembrane helix, and a cytoplasmic C-terminal domain that recruits TRAF adaptors to activate NF-κB and MAPK pathways. It is synthesized as a precursor and cleaved to form the mature receptor. RANK is critical for osteoclastogenesis and also regulates T-cell/dendritic-cell interactions. Post-translational modifications include glycosylation and ubiquitination, which modulate signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF11A Knockout HEK293 Cell Line | EDJ-KQ2841 | Human | 8792 | Details Get a Quote |
| TNFRSF11A Knockout A-549 Cell Line | EDJ-KQ25214 | Human | 8792 | Details Get a Quote |
| TNFRSF11A Knockout HCT 116 Cell Line | EDJ-KQ25216 | Human | 8792 | Details Get a Quote |
| TNFRSF11A Knockout HeLa Cell Line | EDJ-KQ25217 | Human | 8792 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
