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FLASH GENE
Symbol TNFRSF11B contributors: mct/npt/shn - updated : 19-09-2015
HGNC name tumor necrosis factor receptor superfamily, member 11b
HGNC id 11909
Corresponding disease
PDB7 Paget bone disease 7
Location 8q24.12      Physical location : 119.935.796 - 119.964.383
Synonym name
  • osteoprotegerin
  • osteoclastogenesis inhibitory factor
  • tumor necrosis factor receptor superfamily member 11B
  • Synonym symbol(s) OPG, OCIF, TR1, FDCR1, MGC29565
    DNA
    TYPE functioning gene
    STRUCTURE 28.59 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    motif
    text structure two binding sites for HOXC8 (mediating OPG activation in response to BMP stimulation)
  • RUNX2 and SMAD binding element for responsiveness to TGFB1 and RUNX2
  • MAPPING cloned Y linked N status confirmed
    Map see COLEC10
    Physical map
    TRPS1 8q24.11 trichorhinophalangeal syndrome I EIF3S3 8q24.13 eukaryotic translation initiation factor 3, subunit 3 gamma, 40kDa MGC14595 8q24.11 hypothetical protein MGC14595 RAD21 8q24.11 RAD21 homolog (S. pombe) SLC30A8 8q24.11 solute carrier family 30 (zinc transporter), member 8 TRAP25 EXT1 8q24.11 exostoses (multiple) 1 LOC392263 8 similar to RIKEN cDNA A830094I09 gene LOC286091 8q24.12 similar to 40S ribosomal protein S26 TNFRSF11B 8q24.13 tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) COLEC10 8q24.13 collectin sub-family member 10 (C-type lectin) MAL2 8q23 mal, T-cell differentiation protein 2 NOV 8q24.1 nephroblastoma overexpressed gene LOC392264 8 hypothetical gene supported by AK122835 ENPP2 8q24.13 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin) HCP23 8q24.12 cytochrome c, somatic pseudogene TAF2 8q24.12 TAF2 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 150kDa MGC5528 8q24.12 defective in sister chromatid cohesion homolog 1 (S. cerevisiae) MGC14407 8q24.12 hypothetical protein MGC14407 FLJ12428 8q24.12 hypothetical protein FLJ12428 LOC389682 8 similar to collagen type XIV COL14A1 8q24.13 collagen, type XIV, alpha 1 (undulin) MRPL13 8q22.1-q22.3 mitochondrial ribosomal protein L13 MTBP 8q24.1-q24.2 Mdm2, transformed 3T3 cell double minute 2, p53 binding protein (mouse) binding protein, 104kDa SNTB1 8q24.13 syntrophin, beta 1 (dystrophin-associated protein A1, 59kDa, basic component 1) HAS2 8q24.13 hyaluronan synthase 2 MRPS36P3 8q24.13 mitochondrial ribosomal protein S36 pseudogene
    regionally located cen - D8S1016 - D8S522 - TNFRSF11B - D8S1823 - D8S269 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2354 60 401 - - 9168977
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly Homo sapiens
    Digestiveliver   highly Homo sapiens
    Nervousbrain   highly Homo sapiens
    Reproductivefemale systemplacenta  highly Homo sapiens
     male systemtestis  lowly Homo sapiens
    Respiratorylung   highly Homo sapiens
    Urinarykidney   lowly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    Skeletonosteoblast Homo sapiens
    cell lineage lymphoid cells
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text kidney, liver, lung
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four extracytoplasmic cysteine-rich pseudo-repeats typical for the TNFR superfamily, ligand binding domain
  • a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling
  • a small cytoplasmic tail with two DEATH domains, also existing as a secreted form OPG
  • conjugated GlycoP
    mono polymer homomer , dimer , trimer
    HOMOLOGY
    interspecies ortholog to Tnfrsf11b, mus musculus
    ortholog to Tnfrsf11b, Rattus norvegicus
    ortholog to TNFRSF11B, Pan troglodytes
    Homologene
    FAMILY
  • tumor necrosis factor receptor superfamily
  • CATEGORY signaling cytokine , receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text localized to the Weibel-Palade bodies of vascular endothelial cells
    basic FUNCTION
  • cell to cell signaling between stromal cells and osteoclast progenitor
  • can act as a soluble factor in the regulation of bone mass
  • specifically inhibits osteoclastogenesis
  • playing a role in the vascular system
  • involved in RANKL/RANK signaling
  • regulates dendritic cells survival, monocyte chemotaxis, and B cell development and function by ligating TNF family member receptor activator of NF-kappaB ligand (TNFSF11)
  • acts as an autocrine/paracrine growth factor for vascular smooth muscle cells, which might contribute to the progression of atherosclerotic lesions (Corallini 2009)
  • key factor linking bone formation to resorption during bone remodeling
  • expression of TNFRSF11B, TNFRSF11A and TNFSF11 genes exert a crucial role in the progression of Femoral head avascular necrosis (AVN), suggesting their roles in mediating bone homeostasis and potential effects on bone destruction
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS development
    text skeletal development
    PATHWAY
    metabolism
    signaling
    a component
  • involvement of the TNFRSF11A/TNFSF11/TNFRSF11B axis in osteosarcoma biology (Mori 2007)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Osteoclast differentiation factor
  • von Willebrand factor, vWF
  • CTGF significantly bound to TNFRSF11B, which is a decoy receptor of TNFSF11
  • CTGF canceled the inhibitory effect of TNFRSF11B on osteoclast differentiation
  • cell & other
    REGULATION
    activated by upregulated by CD40 (TNFRSF5) stimulation
    ASSOCIATED DISORDERS
    corresponding disease(s) PDB7
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hormone- resistant prostate tumor with good prognosis
    constitutional germinal mutation      
    associated with bone mineral density at different skeletal sites in adult men, but not in women
    constitutional     --over  
    in cirrhotic chronic liver disease, which could modulate bone loss
    constitutional     --over  
    by dendritic cells, increases with maturation and is NF-kappaB-dependent, possibly regulating immune responses in lymphoid tissues
    Susceptibility
  • to osteoporotic fracture (to hip fractures)
  • to the progression of atherosclerosis and cardiovascular disease
  • to periodontitis
  • to coronary artery disease
  • to sporadic Paget bone disease
  • Variant & Polymorphism SNP , other
  • A163-G and T245-G were significantly more common among patients with vertebral fractures
  • 950 TC/1181 GC and 950 CC/1181 CC associated to an increased risk of coronary artery disease
  • TG haplotype of T950C and G1181C polymorphisms in the OPG gene may be useful genetic markers for the prediction of periodontitis (Park 2008)
  • G1181 allele, encoding lysine at codon 3 predisposing to the development of sporadic Paget bone disease
  • Lys3Asn polymorphism increases susceptibility to hip fractures among older white women
  • Candidate gene
    Marker
  • expression of TNFRSF11A, TNFSF11 and TNFRSF11B may be used as diagnostic markers to identify patients at high risk for aggressive Prostate carcinoma 6)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    effective suppression of Prostate carcinoma cell migration by TNFRSF11B via the blockage of TNFSF11 activity represents a potential therapeutic strategy for interfering with prostate tumor metastasis and progression to bone
    ANIMAL & CELL MODELS
  • OPG-/- mice exhibit a decrease in total bone density characterized by severe trabecular and cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures
  • OCIF/OPG knockout mice are viable and fertile but exhibit severe osteoporosis due to enhanced osteoclastogenesis, and marked bone loss accompanied by destruction of growth plate and lack of trabecular bone in their femurs