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

Gene ID: 8600, updated on 19-Mar-2019

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

Genomic context

See TNFSF11 in Genome Data Viewer
Location:
13q14.11
Exon count:
11
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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 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 FunctionsWhat's a GeneRIF?

Phenotypes

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

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 BioSystems

  • Breast cancer, organism-specific biosystem (from KEGG)
    Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • Breast cancer, conserved biosystem (from KEGG)
    Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
  • 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 ...
  • Differentiation Pathway, organism-specific biosystem (from WikiPathways)
    Differentiation Pathway, organism-specific biosystemThis pathway provides an overview of the directed differentiation molecules used to induce early and derivative cell lineages from human pluripotent stem cells. The initial version of this pathway is...
  • 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 (Receptor activator of NFKB (ligand)) Signaling Pathway, organism-specific biosystem (from WikiPathways)
    RANKL/RANK (Receptor activator of NFKB (ligand)) 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...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 
protein binding IPI
Inferred from Physical Interaction
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
 
calcium-mediated signaling ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to leukemia inhibitory factor 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 
ossification IEA
Inferred from Electronic Annotation
more info
 
osteoclast development 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 DNA-binding transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
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 transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
protein homooligomerization IEA
Inferred from Electronic Annotation
more info
 
regulation of actin binding IEA
Inferred from Electronic Annotation
more info
 
regulation of signaling receptor activity IEA
Inferred from Electronic Annotation
more info
 
tooth eruption 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
 

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)

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, ENST00000398795.6
    Conserved Domains (1) summary
    pfam00229
    Location:185313
    TNF; TNF(tumor Necrosis Factor) family
  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
    ENSP00000351347.2, ENST00000358545.6
    Conserved Domains (1) summary
    pfam00229
    Location:112240
    TNF; TNF(tumor Necrosis Factor) family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p12 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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