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    TNFSF11 tumor necrosis factor superfamily member 11 [ Homo sapiens (human) ]

    Gene ID: 8600, updated on 19-Jul-2016
    Official Symbol
    TNFSF11provided by HGNC
    Official Full Name
    tumor necrosis factor superfamily member 11provided by HGNC
    Primary source
    HGNC:HGNC:11926
    See related
    Ensembl:ENSG00000120659 HPRD:04031; MIM:602642; Vega:OTTHUMG00000016807
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ODF; OPGL; sOdf; CD254; OPTB2; RANKL; TNLG6B; TRANCE; hRANKL2
    Summary
    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]
    Orthologs
    Location:
    13q14
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 13 NC_000013.11 (42562736..42608013)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (43136872..43182149)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene fatty acid binding protein 3 pseudogene 2 Neighboring gene uncharacterized LOC105370177 Neighboring gene uncharacterized LOC107984612 Neighboring gene uncharacterized LOC107984611 Neighboring gene family with sequence similarity 216 member B

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Osteopetrosis autosomal recessive 2
    MedGen: C1850126 OMIM: 259710 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

    Description
    Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.
    NHGRI GWA Catalog
    Genome-wide association meta-analysis of cortical bone mineral density unravels allelic heterogeneity at the RANKL locus and potential pleiotropic effects on bone.
    NHGRI GWA Catalog
    Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.
    NHGRI GWA Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    NHGRI GWA Catalog
    Multiple genetic loci for bone mineral density and fractures.
    NHGRI GWA Catalog
    Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.
    NHGRI GWA Catalog
    New sequence variants associated with bone mineral density.
    NHGRI GWA Catalog
    New variants including ARG1 polymorphisms associated with C-reactive protein levels identified by genome-wide association and pathway analysis.
    NHGRI GWA Catalog
    Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
    NHGRI GWA Catalog
    WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.
    NHGRI GWA Catalog

    Replication interactions

    Interaction Pubs
    Knockdown of tumor necrosis factor (ligand) superfamily, member 11 (TNFSF11) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 reduces osteoblast function and significantly decreases the levels of BMP-7 and RANK-L PubMed
    env Induction of the receptor activator of cytokine nuclear factor kappa B ligand (RANKL) is mediated by HIV-1 gp120; the gp120-mediated induction of RANKL is blocked by interferon-gamma PubMed
    Pr55(Gag) gag HIV-1 Gag reduces osteoblast function and significantly reduces the levels of BMP-2, BMP-7, osteocalcin, and RANK-L PubMed
    Tat tat HIV-1 Tat and RANKL/M-CSF enhance osteoclast differentiation and activity by increasing osteoclast differentiation markers, such as cathepsin K and calcitonin receptor, and TRAP PubMed
    tat Co-treatment of osteoblastic cells with HIV-1 Tat and RANKL/M-CSF upregulates c-fos expression and AP-1 activity PubMed
    Vpr vpr HIV-1 Vpr upregulates RANKL expression through its glucocorticoid (GC) co-activator motif (amino acid residues 22-26), an effect that is independent of Vpr-mediated G2 cell cycle arrest PubMed

    Go to the HIV-1, Human Interaction Database

    • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
      Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
    • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • IL6-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL6-mediated signaling events, organism-specific biosystem
      IL6-mediated signaling events
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
      NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
    • NF-kappa B signaling pathway, conserved biosystem (from KEGG)
      NF-kappa B signaling pathway, conserved biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
    • Osteoblast Signaling, organism-specific biosystem (from WikiPathways)
      Osteoblast Signaling, organism-specific biosystem
      Osteoblast Signaling
    • Osteoclast Signaling, organism-specific biosystem (from WikiPathways)
      Osteoclast Signaling, organism-specific biosystem
      Osteoclast Signaling
    • Osteoclast differentiation, organism-specific biosystem (from KEGG)
      Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
    • Osteoclast differentiation, conserved biosystem (from KEGG)
      Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
    • Prolactin signaling pathway, organism-specific biosystem (from KEGG)
      Prolactin signaling pathway, organism-specific biosystemProlactin (PRL) is a polypeptide hormone known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, growth and development, endocrinology and meta...
    • Prolactin signaling pathway, conserved biosystem (from KEGG)
      Prolactin signaling pathway, conserved biosystemProlactin (PRL) is a polypeptide hormone known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, growth and development, endocrinology and meta...
    • RANKL/RANK Signaling Pathway, organism-specific biosystem (from WikiPathways)
      RANKL/RANK Signaling Pathway, organism-specific biosystemRANKL (Receptor activator of nuclear factor-kappa B ligand), RANK (Receptor activator of nuclear factor-kappa B) and the natural decoy receptor of RANKL, OPG (Osteoprotegerin) are three important mol...
    • Rheumatoid arthritis, organism-specific biosystem (from KEGG)
      Rheumatoid arthritis, organism-specific biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • Rheumatoid arthritis, conserved biosystem (from KEGG)
      Rheumatoid arthritis, conserved biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway, organism-specific biosystem (from REACTOME)
      TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway, organism-specific biosystemActivation of NF-kB is fundamental to signal transduction by members of the TNFRSF. Expression of NF-kB target genes is essential for mounting innate immune responses to infectious microorganisms but...
    • TNFR2 non-canonical NF-kB pathway, organism-specific biosystem (from REACTOME)
      TNFR2 non-canonical NF-kB pathway, organism-specific biosystemTumor necrosis factor-alpha (TNFA) exerts a wide range of biological effects through TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Under normal physiological conditions TNFR2 exhibits more restr...
    • TNFs bind their physiological receptors, organism-specific biosystem (from REACTOME)
      TNFs bind their physiological receptors, organism-specific biosystemMembers of the tumour necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) have crucial roles in both innate and adaptive immunity. These members are implicated in various acquir...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    cytokine activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytokine activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    tumor necrosis factor receptor binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    tumor necrosis factor receptor superfamily binding IC
    Inferred by Curator
    more info
    PubMed 
    Process Evidence Code Pubs
    ERK1 and ERK2 cascade IEA
    Inferred from Electronic Annotation
    more info
     
    TNFSF11-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    activation of JUN kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    bone resorption IEA
    Inferred from Electronic Annotation
    more info
     
    calcium ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    cytokine-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    immune response NAS
    Non-traceable Author Statement
    more info
    PubMed 
    mammary gland alveolus development IEA
    Inferred from Electronic Annotation
    more info
     
    mammary gland epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    monocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    organ morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    ossification IEA
    Inferred from Electronic Annotation
    more info
     
    osteoclast differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    osteoclast differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    osteoclast differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    osteoclast proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    paracrine signaling IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of I-kappaB kinase/NF-kappaB signaling IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of MAP kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of bone resorption IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of corticotropin-releasing hormone secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of fever generation by positive regulation of prostaglandin secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of homotypic cell-cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of osteoclast development IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of osteoclast differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein kinase B signaling IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of sequence-specific DNA binding transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein homooligomerization IEA
    Inferred from Electronic Annotation
    more info
     
    tumor necrosis factor-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    tumor necrosis factor-mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    extracellular region NAS
    Non-traceable Author Statement
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IEA
    Inferred from Electronic Annotation
    more info
     
    integral component of plasma membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    tumor necrosis factor ligand superfamily member 11
    Names
    TNF-related activation-induced cytokine
    osteoclast differentiation factor
    osteoprotegerin ligand
    receptor activator of nuclear factor kappa B ligand
    receptor activator of nuclear factor kappa-B ligand
    tumor necrosis factor (ligand) superfamily member 11
    tumor necrosis factor (ligand) superfamily, member 11
    tumor necrosis factor ligand 6B

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008990.1 RefSeqGene

      Range
      5001..50278
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003701.3NP_003692.1  tumor necrosis factor ligand superfamily member 11 isoform 1

      See identical proteins and their annotated locations for NP_003692.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer protein (isoform 1).
      Source sequence(s)
      AL139382, BC117286, BQ007726
      Consensus CDS
      CCDS9384.1
      UniProtKB/Swiss-Prot
      O14788
      UniProtKB/TrEMBL
      Q5T9Y4
      Related
      ENSP00000381775, OTTHUMP00000018328, ENST00000398795, OTTHUMT00000044702
      Conserved Domains (1) summary
      cd00184
      Location:164311
      TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...
    2. NM_033012.3NP_143026.1  tumor necrosis factor ligand superfamily member 11 isoform 2

      See identical proteins and their annotated locations for NP_143026.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding region, compared to variant 1. These differences cause translation initiation at a downstream AUG and an isoform (2) with a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AL139382, BC040889, BQ007726
      Consensus CDS
      CCDS9385.1
      UniProtKB/Swiss-Prot
      O14788
      UniProtKB/TrEMBL
      Q54A98
      Related
      ENSP00000351347, OTTHUMP00000178585, ENST00000358545, OTTHUMT00000044703
      Conserved Domains (1) summary
      cd00184
      Location:91238
      TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p7 Primary Assembly

      Range
      42562736..42608013
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017020803.1XP_016876292.1  

      Related
      ENSP00000444913, ENST00000544862
    2. XM_011535280.2XP_011533582.1  

      See identical proteins and their annotated locations for XP_011533582.1

      UniProtKB/Swiss-Prot
      O14788
      UniProtKB/TrEMBL
      Q54A98
      Conserved Domains (1) summary
      cd00184
      Location:91238
      TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...
    3. XM_017020802.1XP_016876291.1  

    Alternate CHM1_1.1

    Genomic

    1. NC_018924.2 Alternate CHM1_1.1

      Range
      43104338..43149624
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)