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TNFSF11 Gene

protein-coding   GIFtS: 68
GCID: GC13P043136

Tumor Necrosis Factor (Ligand) Superfamily, Member 11

  See TNFSF11-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Tumor Necrosis Factor (Ligand) Superfamily, Member 111 2     TNF-Related Activation-Induced Cytokine2 3
OPGL2 3 5     OPTB22 5
TRANCE2 3 5     CD2542
Osteoclast Differentiation Factor2 3     hRANKL22
Osteoprotegerin Ligand2 3     Receptor Activator Of Nuclear Factor Kappa B Ligand2
Receptor Activator Of Nuclear Factor Kappa-B Ligand2 3     sOdf2
ODF2 3     Tumor Necrosis Factor Ligand Superfamily Member 112
RANKL2 3     CD254 Antigen3

External Ids:    HGNC: 119261   Entrez Gene: 86002   Ensembl: ENSG000001206597   OMIM: 6026425   UniProtKB: O147883   

Export aliases for TNFSF11 gene to outside databases

Previous GC identifers: GC13P041146 GC13P037132 GC13P042073 GC13P040934 GC13P040943 GC13P042034 GC13P023940


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TNFSF11 Gene:
This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for
osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was
shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune
response. T cell activation was reported to induce expression of this gene and lead to an increase of
osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a
signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which
indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related
gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early
differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy.
Two alternatively spliced transcript variants have been found. (provided by RefSeq, Jul 2008)

GeneCards Summary for TNFSF11 Gene:
TNFSF11 (tumor necrosis factor (ligand) superfamily, member 11) is a protein-coding gene. Diseases associated with TNFSF11 include tnfsf11-related autosomal recessive osteopetrosis, and osteopetrosis autosomal recessive 2. GO annotations related to this gene include tumor necrosis factor receptor superfamily binding and cytokine activity. An important paralog of this gene is TNFSF10.

UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788
Function: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation
factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important
regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the
T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral
hypercalcemia of malignancy

Gene Wiki entry for TNFSF11 (RANKL) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000013.10  NC_018924.2  NT_024524.15  
Regulatory elements:
   Regulatory transcription factor binding sites in the TNFSF11 gene promoter:
         STAT1   FOXO4   STAT1beta   STAT3   STAT1alpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): TNFSF11 promoter sequence
   Search Chromatin IP Primers for TNFSF11

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TNFSF11


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 13q14   Ensembl cytogenetic band:  13q14.11   HGNC cytogenetic band: 13q14

TNFSF11 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TNFSF11 gene location

GeneLoc information about chromosome 13         GeneLoc Exon Structure

GeneLoc location for GC13P043136:  view genomic region     (about GC identifiers)

Start:
43,136,872 bp from pter      End:
43,182,149 bp from pter
Size:
45,278 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788 (See protein sequence)
Recommended Name: Tumor necrosis factor ligand superfamily member 11  
Size: 317 amino acids; 35478 Da
Subunit: Homotrimer (Probable). Interacts with TNFRSF11B
1 PDB 3D structure from and Proteopedia for TNFSF11:
3URF (3D)    
Secondary accessions: O14723 Q96Q17 Q9P2Q3
Alternative splicing: 3 isoforms:  O14788-1   O14788-2   O14788-3   

Explore the universe of human proteins at neXtProt for TNFSF11: NX_O14788

Explore proteomics data for TNFSF11 at MOPED

Post-translational modifications: 

  • The soluble form of isoform 1 derives from the membrane form by proteolytic processing (By similarity). The
    cleavage may be catalyzed by ADAM171
  • Glycosylation2 at Asn171, Asn198

  • See TNFSF11 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_003692.1  NP_143026.1  

    ENSEMBL proteins: 
     ENSP00000351347   ENSP00000239849   ENSP00000384042   ENSP00000381775   ENSP00000444913  

    TNFSF11 Human Recombinant Protein Products:

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    R&D Systems Recombinant & Natural Proteins for TNFSF11 (TRANCE/TNFSF11/RANK L)
    Enzo Life Sciences proteins for TNFSF11
    OriGene Purified Protein for TNFSF11
    OriGene Protein Over-expression Lysate for TNFSF11
    OriGene MassSpec for TNFSF11
    OriGene Custom Protein Services for TNFSF11
    GenScript Custom Purified and Recombinant Proteins Services for TNFSF11
    Novus Biologicals TNFSF11 Proteins
    Novus Biologicals TNFSF11 Lysates
    Sino Biological Recombinant Protein for TNFSF11
    Sino Biological Cell Lysate for TNFSF11
    ProSpec Recombinant Protein for TNFSF11
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for TNFSF11 

    TNFSF11 Antibody Products:

    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
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    Novus Biologicals TNFSF11 Antibodies
    Abcam antibodies for TNFSF11
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    TNFSF11 Assay Products:

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    Enzo Life Sciences assays for TNFSF11
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for TNFSF11 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CD: CD molecules
    TNFSF: Tumor necrosis factor (ligand) superfamily

    3 InterPro protein domains:
     IPR006052 TNF_dom
     IPR008983 Tumour_necrosis_fac-like_dom
     IPR017355 TNF_ligand_10/11

    Graphical View of Domain Structure for InterPro Entry O14788

    ProtoNet protein and cluster: O14788

    1 Blocks protein domain: IPB006052 Tumor Necrosis Factor

    UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788
    Similarity: Belongs to the tumor necrosis factor family


    Find genes that share domains with TNFSF11           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TNF11_HUMAN, O14788
    Function: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation
    factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important
    regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the
    T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral
    hypercalcemia of malignancy
    Induction: Up-regulated by T-cell receptor stimulation

         Genatlas biochemistry entry for TNFSF11:
    tumor necrosis factor superfamily,member 11 TNFRSF11A (RANK) and OPG (osteprogerin ligand),localized in T cells
    bone marrow stromal cells,hypertrophic chondrocyte,stimulated by IL1B and TNFRSF11B,expressed in bone,
    brain,heart,kidney,skeletal muscle,skin,cooperating with prostaglandin,mediating osteoclastognesis and bone loss
    through systemic activation of T cells,regulating lymph node organogenesis lymphocyte development and
    interactions between T cells and dendritic cells,activating the antiapoptotic serine threonine kinase AKT/PKB
    through a signal complex involving TRAF6 and SRC

         Summary: 
    During embryonic development, TNFSF11 as signaling molecule affects the following cells:
    Bone: Osteoclasts (Bone Marrow)

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005125cytokine activity NAS9568710
    GO:0005164tumor necrosis factor receptor binding NAS9312132
    GO:0005515protein binding ----
    GO:0032813tumor necrosis factor receptor superfamily binding IC19940926
         
    Find genes that share ontologies with TNFSF11           About GenesLikeMe


    Phenotypes:
         12 MGI mutant phenotypes (inferred from 8 alleles(MGI details for Tnfsf11):
     craniofacial  endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  mortality/aging  no phenotypic analysis 
     reproductive system  skeleton 

    Find genes that share phenotypes with TNFSF11           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for TNFSF11: Tnfsf11tm1Ywc Tnfsf11tm1Pngr Tnfsf11tm1.2Htaka

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TNFSF11
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TNFSF11
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TNFSF11

    miRNA
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    miRTarBase miRNAs that target TNFSF11:
    hsa-mir-18a-5p (MIRT004387)

    Block miRNA regulation of human, mouse, rat TNFSF11 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TNFSF11 (see all 26):
    hsa-miR-323-3p hsa-miR-520d-5p hsa-miR-106a hsa-miR-657 hsa-let-7a-2* hsa-miR-488 hsa-miR-519a hsa-miR-144
    SwitchGear 3'UTR luciferase reporter plasmidTNFSF11 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TNFSF11
    Predesigned siRNA for gene silencing in human, mouse, rat TNFSF11

    Gene Editing
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    Clone
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    OriGene ORF clones in mouse, rat for TNFSF11
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): TNFSF11 (NM_003701)
    Sino Biological Human cDNA Clone for TNFSF11
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TNFSF11
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TNFSF11

    Cell Line
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    Flow Cytometry
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    eBioscience FlowRNA Probe Sets ( VA1-13741) for TNFSF11 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TNF11_HUMAN, O14788: Isoform 1: Cell membrane; Single-pass type II membrane protein
    TNF11_HUMAN, O14788: Isoform 3: Cell membrane; Single-pass type II membrane protein
    TNF11_HUMAN, O14788: Isoform 2: Cytoplasm (By similarity)
    TNF11_HUMAN, O14788: Tumor necrosis factor ligand superfamily member 11, soluble form: Secreted (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    plasma membrane5
    nucleus2
    cytoskeleton1
    endoplasmic reticulum1
    mitochondrion1

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region NAS10708588
    GO:0005615extracellular space IEA--
    GO:0005622intracellular ----
    GO:0005737cytoplasm IEA--
    GO:0005887integral component of plasma membrane NAS9312132

    Find genes that share ontologies with TNFSF11           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TNFSF11 About   (see all 23)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1PEDF Induced Signaling
    MIF Regulation of Innate Immune Cells0.94
    IL-6 Pathway0.61
    MIF Mediated Glucocorticoid Regulation0.94
    STAT3 Pathway0.47
    PEDF Induced Signaling0.73
    Endothelin-1 Signaling Pathway0.46
    all-trans-Retinoic Acid Signaling in Brain0.71
    Cytokine-cytokine receptor interaction0.43
    2TNF Signaling
    TNF Signaling0.50
    TNF Superfamily - Human Ligand-Receptor Interactions and their Associated Functions0.49
    Death Receptor Signaling0.50
    NF-kB (NFkB) Pathway0.46
    3RANK Signaling in Osteoclasts
    RANK Signaling in Osteoclasts0.45
    RANKL/RANK Signaling Pathway0.31
    RANK Pathway0.38
    4ERK Signaling
    Rho Family GTPases0.61
    Molecular Mechanisms of Cancer0.51
    ERK Signaling0.61
    5Akt Signaling
    Akt Signaling0.60
    p38 Signaling0.60


    Find genes that share SuperPaths with TNFSF11           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for TNFSF11
        TNF Superfamily - Human Ligand-Receptor Interactions & their Associated Functions

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TNFSF11 (see all 20)
        TRAF Pathway
    Endothelin-1 Signaling Pathway
    Molecular Mechanisms of Cancer
    Antioxidant Action of Vitamin-C
    TRAIL Pathway

    3 Cell Signaling Technology (CST) Pathways for TNFSF11
        Apoptosis and Autophagy
    Lymphocyte Signaling
    NF-kappaB Signaling

    3 GeneGo (Thomson Reuters) Pathways for TNFSF11
        Development Hedgehog and PTH signaling pathways in bone and cartilage development
    Transcription Role of VDR in regulation of genes involved in osteoporosis
    Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway

    4 BioSystems Pathways for TNFSF11
        RANKL/RANK Signaling Pathway
    IL6-mediated signaling events
    Osteoclast Signaling
    Osteoblast Signaling

    3 Sino Biological Pathways for TNFSF11
        TNF Signaling
    Death Receptor Signaling
    NF-kB (NFkB) Pathway


    5 Kegg Pathways  (Kegg details for TNFSF11):
        Cytokine-cytokine receptor interaction
    NF-kappa B signaling pathway
    Osteoclast differentiation
    Prolactin signaling pathway
    Rheumatoid arthritis

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TNFSF11 (see all 10): 
              Osteogenesis in human mouse rat
              Inflammasomes in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat
              Antigen Presenting Cells in human mouse rat
              Inflammatory Cytokines & Receptors in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TNFSF11

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TNFSF11 (O147882, 3 ENSP000002398494) via UniProtKB, MINT, STRING, and/or I2D (see all 46)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DDAH2O958652, 3MINT-8274654 I2D: score=2 
    ENSG00000206395O958652, 3MINT-8274654 I2D: score=2 
    ENSG00000225635O958652, 3MINT-8274654 I2D: score=2 
    ENSG00000226634O958652, 3MINT-8274654 I2D: score=2 
    ENSG00000227317O958652, 3MINT-8274654 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 33):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001503ossification IEA--
    GO:0002158osteoclast proliferation IEA--
    GO:0002548monocyte chemotaxis IDA15248232
    GO:0006955immune response NAS9312132
    GO:0007257activation of JUN kinase activity IEA--

    Find genes that share ontologies with TNFSF11           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for TNFSF11
      Browse compounds at ApexBio 

    Browse Tocris compounds for TNFSF11 (TNF11)

    2 DrugBank Compounds for TNFSF11    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Denosumab-- 615258-40-7targetantibody18685421 16702197
    LenalidomideCC-5013 (see all 4)191732-72-6targetinhibitor17369076 19370685

    Selected Novoseek inferred chemical compound relationships for TNFSF11 gene (see all 99)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    denosumab 93.7 88 19016581 (5), 19590040 (3), 19092832 (3), 19404943 (2) (see all 58)
    tartrate 65.2 6 14751235 (1), 18565244 (1), 19057837 (1), 16948499 (1) (see all 6)
    1,25 dihydroxy vitamin d3 61.3 13 10913332 (3), 19464673 (2), 12364326 (1), 17053039 (1) (see all 10)
    zoledronic acid 61.2 21 14753746 (5), 19670154 (4), 18289304 (2), 16938523 (1) (see all 8)
    hcc-1 60.9 3 12773123 (3)
    pge2 52.4 79 20112374 (5), 15068113 (5), 17951042 (5), 17559635 (4) (see all 31)
    calcitriol 50.7 25 19073256 (2), 12421995 (1), 14693199 (1), 19732857 (1) (see all 14)
    mip 1alpha 49.9 5 16211583 (2), 12965277 (1), 17506059 (1)
    risedronate 49.3 9 19301089 (3), 17967134 (2), 18275008 (2), 15777635 (1) (see all 5)
    alendronate 48.8 6 19574937 (3), 17966399 (1), 19092832 (1)



    Find genes that share compounds with TNFSF11           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TNFSF11 gene (2 alternative transcripts): 
    NM_003701.3  NM_033012.3  

    Unigene Cluster for TNFSF11:

    Tumor necrosis factor (ligand) superfamily, member 11
    Hs.333791  [show with all ESTs]
    Unigene Representative Sequence: NM_033012
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000358545 ENST00000239849 ENST00000405262(uc001uyt.2) ENST00000398795(uc001uyu.2)
    ENST00000544862
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate TNFSF11 (see all 26):
    hsa-miR-323-3p hsa-miR-520d-5p hsa-miR-106a hsa-miR-657 hsa-let-7a-2* hsa-miR-488 hsa-miR-519a hsa-miR-144
    SwitchGear 3'UTR luciferase reporter plasmidTNFSF11 3' UTR sequence
    Inhib. RNA
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    eBioscience FlowRNA Probe Sets ( VA1-13741) for TNFSF11 

    Additional mRNA sequence: 

    AB037599.1 AB061227.1 AB064268.1 AB064269.1 AB064270.1 AF013171.1 AF019047.1 AF053712.1 
    BC040889.1 BC074823.2 BC074890.2 BC117286.1 BC117288.1 

    4 DOTS entries:

    DT.100021499  DT.208116  DT.91692886  DT.95154602 

    23 AceView cDNA sequences:

    AV653073 BC074890 AB061227 AB064268 AB064269 BC040889 NM_033012 BC074823 
    AB064270 NM_003701 AB037599 BX105834 BQ007726 AA504211 AF019047 AA504450 
    AF013171 BM893658 BM564083 AF053712 BM966907 AI808584 CK823311 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TNFSF11 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CTGGAACCTG
    TNFSF11 Expression
    About this image


    TNFSF11 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Bone (Muscoskeletal System)    fully expand to see all 2 entries
             Bone Marrow
     
     Smooth Muscle (Muscoskeletal System)
             Juxtaglomerular Cells Afferent Arteriole
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Kidney (Urinary System)
             Juxtaglomerular Cells Afferent Arteriole
    TNFSF11 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TNFSF11 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.333791

    UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788
    Tissue specificity: Highest in the peripheral lymph nodes, weak in spleen, peripheral blood Leukocytes, bone
    marrow, heart, placenta, skeletal muscle, stomach and thyroid

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TNFSF11 (see all 10): 
              Osteogenesis in human mouse rat
              Inflammasomes in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat
              Antigen Presenting Cells in human mouse rat
              Inflammatory Cytokines & Receptors in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of chordates.

    Orthologs for TNFSF11 gene from Selected species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tnfsf111 , 5 tumor necrosis factor (ligand) superfamily, member more1, 5 83.07(n)1
    85.08(a)1
      14 (41.26 cM)5
    219431  NM_011613.31  NP_035743.21 
     782774465 
    chicken
    (Gallus gallus)
    Aves TNFSF111 tumor necrosis factor (ligand) superfamily, member more 68.41(n)
    61.45(a)
      428067  NM_001083361.1  NP_001076830.1 
    lizard
    (Anolis carolinensis)
    Reptilia TNFSF116
    tumor necrosis factor (ligand) superfamily, member...
    62(a)
    1 ↔ 1
    3(70126679-70153136)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia tnfsf111 tumor necrosis factor (ligand) superfamily, member more 54.26(n)
    45.04(a)
      100038074  XM_002938043.2  XP_002938089.1 
    zebrafish
    (Danio rerio)
    Actinopterygii tnfsf116
    tumor necrosis factor (ligand) superfamily, member...
    23(a)
    1 ↔ 1
    9(18539506-18559516) ENSDARG00000068141


    ENSEMBL Gene Tree for TNFSF11 (if available)
    TreeFam Gene Tree for TNFSF11 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TNFSF11 gene
    TNFSF102  
    1 SIMAP similar gene for TNFSF11 using alignment to 2 protein entries:     TNF11_HUMAN (see all proteins):
    hRANKL 3

    Find genes that share paralogs with TNFSF11           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for TNFSF11
    PGOHUM00000239976


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TNFSF11 (see all 1131)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 13 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0374244
    Osteopetrosis, autosomal recessive 2 (OPTB2)4--see VAR_0374242 M K mis40--------
    rs1411280311,2
    C--23939807(+) CTGAG-/AAAAAAA 1 -- us2k10--------
    rs716962651,2
    C--23942899(+) TTAAA-/ATATATA 1 -- int10--------
    rs95331521,2
    C,A,H--24079204(+) cccacC/Tgggag 1 -- us2k12Minor allele frequency- T:0.25NA 4
    rs1391755861,2
    --24079217(+) ATGAAC/TAACTC 1 -- us2k10--------
    rs1917207621,2
    --24079232(+) CGTGCA/CGCGTT 1 -- us2k10--------
    rs1846382041,2
    --24079233(+) GTGCCA/GCGTTA 1 -- us2k10--------
    rs74893781,2
    C,H--24079235(+) gccgcC/Gttaag 1 -- us2k19Minor allele frequency- G:0.00NA WA CSA 250
    rs1151269571,2
    F--24079257(+) TTCTTG/ATGAGG 1 -- us2k11Minor allele frequency- A:0.03WA 118
    rs1141440791,2
    F--24079265(+) AGGGTC/TCGCAG 1 -- us2k11Minor allele frequency- T:0.02WA 118

    HapMap Linkage Disequilibrium report for TNFSF11 (43136872 - 43182149 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for TNFSF11:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2747320CNV Deletion23290073
    esv33319CNV Loss17666407
    nsv832593CNV Gain17160897

    Human Gene Mutation Database (HGMD): TNFSF11
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TNFSF11
    DNA2.0 Custom Variant and Variant Library Synthesis for TNFSF11

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 602642   
    OMIM disorders: 259710  
    UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788
  • Osteopetrosis, autosomal recessive 2 (OPTB2) [MIM:259710]: A rare genetic disease characterized by
    abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe
    autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form
    occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with
    macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and
    hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.
    OPTB2 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development.
    Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for TNFSF11 (see all 24):    
    About MalaCards
    tnfsf11-related autosomal recessive osteopetrosis    osteopetrosis autosomal recessive 2    synovitis    paget disease, juvenile
    cherubism    osteopetrosis    chronic apical periodontitis    cholesteatoma
    osteopetrosis autosomal recessive 1    multicentric reticulohistiocytosis    periodontitis    periapical granuloma
    osteosclerosis    villonodular synovitis    hemophilic arthropathy    osteoporosis, postmenopausal
    pigmented villonodular synovitis    humoral hypercalcemia of malignancy    arthropathy    paget's disease of bone

    6 diseases from the University of Copenhagen DISEASES database for TNFSF11:
    Osteoporosis     Periodontal disease     Rheumatoid arthritis     Osteopetrosis
    Multiple myeloma     Giant cell tumor

    Find genes that share disorders with TNFSF11           About GenesLikeMe

    Selected Novoseek inferred disease relationships for TNFSF11 gene (see all 93)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    bone destruction 90.1 70 16144909 (4), 12469211 (3), 10995794 (2), 12223101 (2) (see all 48)
    bone diseases 86.4 85 12424190 (3), 12684416 (3), 19185505 (2), 15205949 (2) (see all 60)
    osteolysis 85.3 98 17683568 (5), 19590968 (5), 20215062 (4), 19502684 (3) (see all 56)
    bone loss 85 114 12707582 (3), 12379618 (3), 14690142 (2), 16806459 (2) (see all 71)
    osteolytic 84.9 57 11870668 (3), 15044512 (2), 12684416 (2), 12665629 (2) (see all 40)
    osteoporosis 82.6 80 19229472 (3), 19352306 (3), 15068494 (2), 17634142 (2) (see all 60)
    paget disease, juvenile 76.2 2 16491292 (1), 17174136 (1)
    osteoporosis postmenopausal 75.7 28 17895323 (2), 18375161 (2), 15068494 (1), 17684931 (1) (see all 23)
    rheumatoid arthritis 75 84 16301197 (2), 15476205 (2), 18576301 (2), 12429533 (2) (see all 64)
    bone metastases 72.6 39 19360288 (3), 17195907 (3), 19344283 (3), 18685421 (3) (see all 24)

    Genetic Association Database (GAD): TNFSF11
    Human Genome Epidemiology (HuGE) Navigator: TNFSF11 (39 documents)

    Export disorders for TNFSF11 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TNFSF11 gene, integrated from 10 sources (see all 1439):
    (articles sorted by number of sources associating them with TNFSF11)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. (PubMed id 9312132)1, 2, 3, 9 Wong B.R....Choi Y. (J. Biol. Chem. 1997)
    2. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. (PubMed id 9367155)1, 2, 3, 9 Anderson D.M....Galibert L. (Nature 1997)
    3. Association of TNFSF11 gene promoter polymorphisms with bone mineral density in postmenopausal women. (PubMed id 16730419)1, 4, 9 Mencej S....Marc J. (Maturitas 2006)
    4. Genetic variations in genes encoding RANK, RANKL, and OPG in rheumatoid arthritis: a case-control study. (PubMed id 20231205)1, 4, 9 Assmann G....Wieczorek S. (J. Rheumatol. 2010)
    5. Associations between HLA-DRB1, RANK, RANKL, OPG, and IL-17 genotypes and disease severity phenotypes in Japanese patients with early rheumatoid arthritis. (PubMed id 17876645)1, 4, 9 Furuya T....Kotake S. (Clin. Rheumatol. 2007)
    6. Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men. (PubMed id 16249885)1, 4, 9 Hsu Y.H....Xu X. (Hum. Genet. 2006)
    7. Evaluation of RANK/RANKL/OPG gene polymorphisms in aggressive periodontitis. (PubMed id 16953816)1, 4, 9 Soedarsono N....Kojima T. (J. Periodont. Res. 2006)
    8. Interaction between RANKL and HLA-DRB1 genotypes may contribute to younger age at onset of seropositive rheumatoid arthritis in an inception cohort. (PubMed id 15476205)1, 4, 9 Wu H....Tsao B.P. (Arthritis Rheum. 2004)
    9. The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density. (PubMed id 19131500)1, 4, 9 Mencej-Bedrac S....Marc J. (J. Mol. Endocrinol. 2009)
    10. Multiple genetic loci for bone mineral density and fractures. (PubMed id 18445777)1, 4, 9 Styrkarsdottir U....Stefansson K. (N. Engl. J. Med. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 8600 HGNC: 11926 AceView: TNFSF11 Ensembl:ENSG00000120659 euGenes: HUgn8600
    ECgene: TNFSF11 Kegg: 8600 H-InvDB: TNFSF11

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for TNFSF11 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TNFSF11 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TNFSF11 gene:
    Search GeneIP for patents involving TNFSF11

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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