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Symbol TNFRSF11A contributors: mct - updated : 22-05-2018
HGNC name tumor necrosis factor receptor superfamily, member 11a, NFKB activator
HGNC id 11908
Corresponding disease
DOSCO2 dysosteosclerosis 2
HEPOD polyostotic osteolytic dysplasia, hereditary expansile
OPTIGD osteopetrosis with immunoglobulin defect
PDB2 Paget bone disease 2
Location 18q21.33      Physical location : 59.992.547 - 60.053.502
Synonym name
  • tumor necrosis factor receptor superfamily, member 11a, activator of NFKB
  • CD265 antigen
  • osteoclast differentiation factor receptor
  • loss of heterozygosity, 18, chromosomal region 1
  • receptor activator of NF-KB
  • Synonym symbol(s) RANK, EVI36, ODGR, TRANCER, CD265, FEO, LOH18CR1, ODFR, OFE, OPTB7, OSTS
    TYPE functioning gene
    STRUCTURE 62.81 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3133 63.6 616 - 2008 18606301
    9 - 3809 - 263 - 2008 18606301
    isoform delta9
    7 - 3642 - 299 - 2008 18606301
    isoform delta7,8,9
    8 - 3756 - 337 - 2008 18606301
    isoform delta8,9
    10 splicing 4551 - 602 normal brain 2013 23664977
  • TNFRSF11A_e5a
  • lacks 42 nucleotides from exon 5, giving rise to a novel shorter form of exon 5, named exon 5a
  • truncation of thirteen amino acids of the third and fourth TNFR motifs of the extracellular part of the receptor
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     intestinesmall intestine   
    Endocrineadrenal gland    
    Lymphoid/Immunelymph node    
    Respiratoryrespiratory tractlarynx   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell
    Skeletonosteoclast Homo sapiens
    cell lineage osteoclast precursors
    cell lines
    at STAGE
  • two extracellular cysteine-rich pseudo repeats typical for TNFR superfamily
  • a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling
  • a cytoplasmic tail lacking the DEATH domain
  • a TRAF-independent motif (IVVY(535-538), which is dispensable for the activation of TRAF-induced signaling pathways but essential for osteoclast lineage commitment
  • mono polymer homomer , trimer
    interspecies homolog to murine Tnfrsf11a
  • tumor necrosis factor receptor superfamily
  • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • intrinsic hematopoietic cell surface receptor
  • receptor activator of NFKB, involved in RANKL/RANK signaling
  • stimulator of JUN kinase
  • adaptor of TRAFs TNFR-associated factors,mediating osteoprotegerin ligand (TNFSF11) ligand effects for osteoclastogenesis and regulating bone mass and calcium metabolism
  • TNFRSF11A signaling pathway plays an important role in bone remodeling
  • role for TNFRSF11A/ERK-mediated signaling in normal osteoblasts chemotactic migration during bone remodeling that is altered or lost during osteosarcoma tumorigenesis
  • 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
  • potential role for TNFRSF11A, the corresponding gene of which is a direct binding target of KLF5, in tumour cell proliferation and invasiveness
  • may have different roles in skeletal development and metabolism
    metabolism metal
    signaling signal transduction
    TNFSF11/TNFRSF11A signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover
    a component
  • forms a complex with LYN, the tyrosine phosphatase, PTPN6, and the adapter protein, Grb2-associated binder 2 (GAB2)
  • involvement of the TNFRSF11A/TNFSF11/TNFRSF11B axis in osteosarcoma biology
    small molecule
  • interacting with TRAF6 at different sites and leading to NF-kappa B activation,via MAP3K14
  • interacting with TRAF2 and leading to JNK activation
  • interacting with TRAF5
  • expression of retro-viral receptor, XPR1, is regulated by TNFSF11-TNFRSF11A signaling
  • TNFSF11 and TNFRSF11A interaction acts through MEK/ERK, which in turn activates NFKB, resulting in the activation of ICAM1 and contributing to the migration of human lung cancer cells
  • SIGLEC15 links TNFSF11-TNFSFR11-NFATC1 signaling with ITAM-mediated intracellular signaling cascades during functional osteoclast development
  • FAM102A is a novel TNFRSF11A signaling component controlling TNFRSF11A-mediated osteoclast formation
  • TNFSF11, TNFRSF11A signalling pathway can be inhibited by cleavage of TNFRSF11A instead of targeting TNFSF11
  • interaction of TNFRSF11A, a member of the tumour necrosis factor receptor superfamily, with TNFSF11 is crucial for the formation, function and survival of osteoclasts
  • TNFRSF11A is also known as TNFSF11 receptor, and its signaling plays a critical role in osteoclastogenesis
  • interaction between TNFSF11 and its receptor TNFRSF11A is essential for the differentiation and bone resorbing capacity of the osteoclast
  • OSCAR-collagen interaction stimulates TNFRSF11A-dependent osteoclastogenesis
  • RELB is necessary for the effective production of downstream TNFRSF11A(+) mTEC (medullary Thymic epithelial cells) progenitors
  • role for TNFRSF11A as a key regulator of Ca(2+)storage and ATP2A1 activity, ultimately affecting denervated skeletal muscle function
  • TNFRSF11A recruits TRAF6 to TRAF6-binding sites (T6BSs) in the TNFRSF11A cytoplasmic tail (RANKcyto) to trigger downstream osteoclastogenic signaling cascades
  • VAV3 is a novel TRAF6 interaction partner that functions in the activation of cooperative signaling between TRAF6-binding sites (T6BSs) and the IVVY motif in the TNFRSF11A signaling complex
  • cell & other
    induced by insulin that induces TNFRSF11A expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation
    corresponding disease(s) HEPOD , PDB2 , OPTIGD , DOSCO2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    associated with bone mineral density at different skeletal sites in adult men, but not in women
  • to osteoporosis
  • to Paget disease
  • to breast cancer (BC) and bone metastasis (BM)
  • Variant & Polymorphism other
  • rs3018362 strongly associated with Paget disease
  • TNFRSF11A SNP rs34945627 has a high allelic frequency in patients with breast cancer (BC) and bone metastasis (BM), and is associated with decreased disease-free survival (DFS) and overall survival (OS)
  • Candidate gene
  • 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
    generation of TNFRSF11A-antagonists is a promising strategy for the exploration of new therapeutics against osteoporosis
  • persistence of bone erosion and synovial osteoclasts in Rank-deficient mice, but bone erosion and osteoclast formation were reduced