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    TNFSF11 TNF superfamily member 11 [ Homo sapiens (human) ]

    Gene ID: 8600, updated on 19-Sep-2021

    Summary

    Official Symbol
    TNFSF11provided by HGNC
    Official Full Name
    TNF superfamily member 11provided by HGNC
    Primary source
    HGNC:HGNC:11926
    See related
    Ensembl:ENSG00000120659 MIM:602642
    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]
    Expression
    Biased expression in lymph node (RPKM 4.9), appendix (RPKM 2.0) and 6 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See TNFSF11 in Genome Data Viewer
    Location:
    13q14.11
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 13 NC_000013.11 (42562736..42608013)
    105.20201022 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 long intergenic non-protein coding RNA 2341 Neighboring gene VISTA enhancer hs1393 Neighboring gene uncharacterized LOC107984611 Neighboring gene family with sequence similarity 216 member B

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Autosomal recessive osteopetrosis 2
    MedGen: C1850126 OMIM: 259710 GeneReviews: Not available
    Compare labs
    Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.
    GeneReviews: Not available
    Genome-wide association meta-analysis of cortical bone mineral density unravels allelic heterogeneity at the RANKL locus and potential pleiotropic effects on bone.
    GeneReviews: Not available
    Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.
    GeneReviews: Not available
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    GeneReviews: Not available
    Multiple genetic loci for bone mineral density and fractures.
    GeneReviews: Not available
    Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.
    GeneReviews: Not available
    New sequence variants associated with bone mineral density.
    GeneReviews: Not available
    New variants including ARG1 polymorphisms associated with C-reactive protein levels identified by genome-wide association and pathway analysis.
    GeneReviews: Not available
    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.
    GeneReviews: Not available
    WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.
    GeneReviews: Not available

    HIV-1 interactions

    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

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables cytokine activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables tumor necrosis factor receptor binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables tumor necrosis factor receptor superfamily binding IC
    Inferred by Curator
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in ERK1 and ERK2 cascade IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in TNFSF11-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in bone resorption IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in calcium ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in calcium-mediated signaling ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to leukemia inhibitory factor IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cytokine-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in immune response NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in mammary gland alveolus development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in mammary gland epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in monocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in ossification IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in osteoclast development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in osteoclast differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in osteoclast differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in osteoclast differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in osteoclast proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in paracrine signaling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of DNA-binding transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of JNK cascade IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of MAP kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of bone resorption IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of corticotropin-releasing hormone secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of fever generation by positive regulation of prostaglandin secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in positive regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of homotypic cell-cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of osteoclast development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of osteoclast differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of protein kinase B signaling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of actin binding IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in tooth eruption IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in tumor necrosis factor-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    located_in extracellular space IEA
    Inferred from Electronic Annotation
    more info
     
    located_in integral component of plasma membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     

    General protein information

    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
    tumor necrosis factor (ligand) superfamily, member 11
    tumor necrosis factor ligand 6B
    tumor necrosis factor superfamily member 11

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_003701.4NP_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
      ENSP00000381775.3, ENST00000398795.7
      Conserved Domains (1) summary
      pfam00229
      Location:185313
      TNF; TNF(tumor Necrosis Factor) family
    2. NM_033012.4NP_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
      ENSP00000351347.2, ENST00000358545.6
      Conserved Domains (1) summary
      pfam00229
      Location:112240
      TNF; TNF(tumor Necrosis Factor) family

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p13 Primary Assembly

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

    mRNA and Protein(s)

    1. XM_017020803.2XP_016876292.1  tumor necrosis factor ligand superfamily member 11 isoform X2

      UniProtKB/Swiss-Prot
      O14788
      UniProtKB/TrEMBL
      Q54A98
      Related
      ENSP00000444913.1, ENST00000544862.5
      Conserved Domains (1) summary
      pfam00229
      Location:112240
      TNF; TNF(tumor Necrosis Factor) family
    2. XM_011535280.2XP_011533582.1  tumor necrosis factor ligand superfamily member 11 isoform X2

      See identical proteins and their annotated locations for XP_011533582.1

      UniProtKB/Swiss-Prot
      O14788
      UniProtKB/TrEMBL
      Q54A98
      Conserved Domains (1) summary
      pfam00229
      Location:112240
      TNF; TNF(tumor Necrosis Factor) family
    3. XM_017020802.1XP_016876291.1  tumor necrosis factor ligand superfamily member 11 isoform X1

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