TNFRSF11B (Osteoprotegerin) Gene
Key regulator of bone remodeling and RANK/RANKL signaling pathway
Gene Information Card
| Symbol | TNFRSF11B |
|---|---|
| Full Name | TNF Receptor Superfamily Member 11b (Osteoprotegerin) |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.12 |
| NCBI Gene ID | 4982 ncbi.nlm.nih.gov/gene/4982 |
| Ensembl ID | ENSG00000164761 |
| UniProt ID | O00300 |
| OMIM ID | 602643 |
| HGNC ID | 11909 |
| Aliases | OPG, OCIF, TR1, MGC29565 |
Description
The TNFRSF11B gene encodes osteoprotegerin (OPG), a soluble decoy receptor of the tumor necrosis factor (TNF) receptor superfamily. OPG binds to RANKL (TNFSF11) and inhibits RANKL-mediated osteoclastogenesis, thereby regulating bone resorption and bone density. It also plays roles in vascular calcification and immune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Juvenile Paget disease (idiopathic hyperphosphatasia) | Loss-of-function mutations in TNFRSF11B reduce OPG activity, leading to uncontrolled RANKL signaling, excessive osteoclast activity, and bone deformities. | OMIM #239000; multiple homozygous/compound heterozygous mutations reported |
| Osteoporosis | Reduced OPG levels or altered OPG/RANKL ratio contribute to increased bone resorption and low bone mineral density. | GWAS and association studies (NCBI Gene, ClinVar) |
| Paget disease of bone (sporadic) | Polymorphisms in TNFRSF11B (e.g., rs3102735) are associated with increased susceptibility. | OMIM #602643; multiple case-control studies |
| Vascular calcification | OPG deficiency in animal models leads to arterial calcification; human studies link low OPG to vascular disease. | Experimental and clinical evidence (UniProt, NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 24.5 | High |
| Heart | 18.2 | High |
| Kidney | 15.8 | Medium |
| Liver | 12.1 | Medium |
| Bone marrow | 10.3 | Medium |
| Skeletal muscle | 6.7 | Low |
| Brain | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoblasts | 20.5 | Primary osteoblasts; high OPG secretion |
| HUVEC (endothelial) | 15.2 | Moderate expression |
| HEK293 | 12.8 | Commonly used for recombinant OPG production |
| HeLa | 8.1 | Low expression |
| MCF7 | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.349C>T (p.Arg117*) | Nonsense | Rare | Loss of function; truncation of OPG; associated with juvenile Paget disease |
| c.862G>A (p.Gly288Arg) | Missense | Rare | Impaired RANKL binding; dominant-negative effect suspected |
| c.1216C>T (p.Arg406Cys) | Missense | Rare | Reduced secretion and activity; reported in Paget disease |
| rs3102735 (intronic variant) | SNP | ~15% in European populations | Associated with altered OPG levels and Paget disease risk |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg117*) lead to truncated OPG lacking functional domains, resulting in complete loss of RANKL inhibition.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TNFRSF11B.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly288Arg) may produce OPG variants that interfere with wild-type OPG function, reducing overall inhibitory capacity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RANKL/RANK signaling pathway (Reactome: R-HSA-5663202)
• Osteoclast differentiation (KEGG: hsa04380)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
Protein Summary
Osteoprotegerin (OPG) is a 401-amino acid secreted glycoprotein (UniProt O00300) that functions as a decoy receptor for RANKL. It contains four cysteine-rich domains (CRD) in the N-terminal region responsible for RANKL binding, and two death domains (DD) in the C-terminal region. OPG inhibits osteoclastogenesis by preventing RANKL from binding to its receptor RANK on osteoclast precursors. It also binds TRAIL (TNFSF10) and may modulate apoptosis. OPG is widely expressed in bone, lung, heart, kidney, and vascular tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF11B Knockout HEK293 Cell Line | EDJ-KQ50492 | Human | 4982 | Details Get a Quote |
| TNFRSF11B Knockout HeLa Cell Line | EDJ-KQ54046 | Human | 4982 | Details Get a Quote |
| TNFRSF11B Knockout A-549 Cell Line | EDJ-KQ62534 | Human | 4982 | Details Get a Quote |
| TNFRSF11B Knockout HCT 116 Cell Line | EDJ-KQ71006 | Human | 4982 | Details Get a Quote |
