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TNFRSF11A TNF receptor superfamily member 11a [ Homo sapiens (human) ]

Gene ID: 8792, updated on 11-Sep-2019

Summary

Official Symbol
TNFRSF11Aprovided by HGNC
Official Full Name
TNF receptor superfamily member 11aprovided by HGNC
Primary source
HGNC:HGNC:11908
See related
Ensembl:ENSG00000141655 MIM:603499
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
FEO; OFE; ODFR; OSTS; PDB2; RANK; CD265; OPTB7; TRANCER; LOH18CR1
Summary
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptors can interact with various TRAF family proteins, through which this receptor induces the activation of NF-kappa B and MAPK8/JNK. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Paget disease of bone. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2012]
Expression
Biased expression in duodenum (RPKM 14.3), colon (RPKM 11.6) and 10 other tissues See more
Orthologs

Genomic context

See TNFRSF11A in Genome Data Viewer
Location:
18q21.33
Exon count:
12
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 18 NC_000018.10 (62325287..62391288)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (59992520..60054943)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene phosphatidylinositol glycan anchor biosynthesis class N Neighboring gene RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing Neighboring gene ribosomal protein L17 pseudogene 44 Neighboring gene ACTB pseudogene 9

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
Familial expansile osteolysis
MedGen: C0432292 OMIM: 174810 GeneReviews: Not available
Compare labs
Osteopetrosis autosomal recessive 7
MedGen: C2676766 OMIM: 612301 GeneReviews: Not available
Compare labs
Paget disease of bone 2, early-onset
MedGen: C4085251 OMIM: 602080 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Discovery and fine mapping of serum protein loci through transethnic meta-analysis.
NHGRI GWA Catalog
Genome-wide association identifies three new susceptibility loci for Paget's disease of bone.
NHGRI GWA Catalog
Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone.
NHGRI GWA Catalog
Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.
NHGRI GWA Catalog
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
NHGRI GWA Catalog
Multiple genetic loci for bone mineral density and fractures.
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
Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.
NHGRI GWA Catalog

Pathways from BioSystems

  • Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
    Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
  • 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 ...
  • 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...
  • 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...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cytokine binding IPI
Inferred from Physical Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor activity TAS
Traceable Author Statement
more info
PubMed 
transmembrane signaling receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
tumor necrosis factor-activated receptor activity ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
Process Evidence Code Pubs
TNFSF11-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
adaptive immune response IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell-cell signaling TAS
Traceable Author Statement
more info
PubMed 
circadian temperature homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
lymph node development IEA
Inferred from Electronic Annotation
more info
 
mammary gland alveolus development IEA
Inferred from Electronic Annotation
more info
 
monocyte chemotaxis NAS
Non-traceable Author Statement
more info
PubMed 
multinuclear osteoclast differentiation IEA
Inferred from Electronic Annotation
more info
 
ossification IEA
Inferred from Electronic Annotation
more info
 
osteoclast differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
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 IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of JUN kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of bone resorption IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of fever generation by positive regulation of prostaglandin secretion ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
response to cytokine IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to interleukin-1 ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
response to lipopolysaccharide ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
response to radiation IEA
Inferred from Electronic Annotation
more info
 
response to tumor necrosis factor ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
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
cytosol IDA
Inferred from Direct Assay
more info
 
external side of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
tumor necrosis factor receptor superfamily member 11A
Names
Paget disease of bone 2
loss of heterozygosity, 18, chromosomal region 1
osteoclast differentiation factor receptor
receptor activator of NF-KB
receptor activator of nuclear factor-kappa B
tumor necrosis factor receptor superfamily, member 11a, NFKB activator

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_008098.1 RefSeqGene

    Range
    4973..67396
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_194

mRNA and Protein(s)

  1. NM_001270949.1NP_001257878.1  tumor necrosis factor receptor superfamily member 11A isoform 2 precursor

    See identical proteins and their annotated locations for NP_001257878.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as delta9) lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964, HE647782
    Consensus CDS
    CCDS74227.1
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Related
    ENSP00000479567.1, ENST00000616710.4
    Conserved Domains (1) summary
    cd13411
    Location:33195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
  2. NM_001270950.1NP_001257879.1  tumor necrosis factor receptor superfamily member 11A isoform 3 precursor

    See identical proteins and their annotated locations for NP_001257879.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, also known as delta8,9) lacks two exons in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964, HE649916
    Consensus CDS
    CCDS74228.1
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Related
    ENSP00000482466.1, ENST00000617039.4
    Conserved Domains (2) summary
    cd13411
    Location:33195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
    pfam05454
    Location:173258
    DAG1; Dystroglycan (Dystrophin-associated glycoprotein 1)
  3. NM_001270951.2NP_001257880.1  tumor necrosis factor receptor superfamily member 11A isoform 4 precursor

    See identical proteins and their annotated locations for NP_001257880.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4, also known as delta7,8,9) lacks three exons in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 4), compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964
    Consensus CDS
    CCDS59324.1
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Related
    ENSP00000269485.7, ENST00000269485.11
    Conserved Domains (1) summary
    cd13411
    Location:33195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
  4. NM_001278268.2NP_001265197.1  tumor necrosis factor receptor superfamily member 11A isoform 5 precursor

    See identical proteins and their annotated locations for NP_001265197.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5, also called RANK-e5a) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (5) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AB209762, AC100843, DA403964, HF584702
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Conserved Domains (1) summary
    cd13411
    Location:33181
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
  5. NM_003839.4NP_003830.1  tumor necrosis factor receptor superfamily member 11A isoform 1 precursor

    See identical proteins and their annotated locations for NP_003830.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AB209762, AC100843, AF018253, DA403964
    Consensus CDS
    CCDS11980.1
    UniProtKB/Swiss-Prot
    Q9Y6Q6
    Related
    ENSP00000465500.1, ENST00000586569.3
    Conserved Domains (1) summary
    cd13411
    Location:33195
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p13 Primary Assembly

    Range
    62325287..62391288
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011526245.2XP_011524547.1  tumor necrosis factor receptor superfamily member 11A isoform X2

    Conserved Domains (1) summary
    cl22855
    Location:109159
    TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
  2. XM_011526244.2XP_011524546.1  tumor necrosis factor receptor superfamily member 11A isoform X1

    Conserved Domains (1) summary
    cd13411
    Location:33200
    TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
  3. XM_017026064.1XP_016881553.1  tumor necrosis factor receptor superfamily member 11A isoform X2

    Conserved Domains (1) summary
    cl22855
    Location:109159
    TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
  4. XM_017026065.1XP_016881554.1  tumor necrosis factor receptor superfamily member 11A isoform X3

  5. XM_017026066.1XP_016881555.1  tumor necrosis factor receptor superfamily member 11A isoform X4

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