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

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; AllianceGenome:HGNC:11908
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; TRANCE-R
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: mouse all
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Genomic context

Location:: 18q21.33

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (62325310..62391288)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (62528176..62594158)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (59992543..60058521)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Elevated tissue expression of RANKL and RANK is associated with poorer survival rates in pancreatic cancer patients.
Title: Elevated tissue expression of RANKL and RANK is associated with poorer survival rates in pancreatic cancer patients.
B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.
Title: B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.
TNFRSF11A variants contribute to systemic autoinflammatory diseases: A case series of 12 patients.
Title: TNFRSF11A variants contribute to systemic autoinflammatory diseases: A case series of 12 patients.
Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).
Title: Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).
Assessment of RANK/RANK-L prevalence and clinical significance in NSCLC European Thoracic Oncology Platform Lungscape cohort and SPLENDOUR randomized clinical trial.
Title: Assessment of RANK/RANK-L prevalence and clinical significance in NSCLC European Thoracic Oncology Platform Lungscape cohort and SPLENDOUR randomized clinical trial.
The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies.
Title: The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies.
The Effect of Osteoprotectin (OPG)/Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL)/Receptor Activator of Nuclear Factor-kappaB (RANK) Gene Methylation on Aortic Valve Calcified.
Title: The Effect of Osteoprotectin (OPG)/Receptor Activator of Nuclear Factor-κB Ligand (RANKL)/Receptor Activator of Nuclear Factor-κB (RANK) Gene Methylation on Aortic Valve Calcified.
Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.
Title: Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.
RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages.
Title: RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages.
Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.
Title: Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.

Submit: New GeneRIF Correction See all GeneRIFs (235)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-147772 (e-PCR)
- UniSTS:172875

NoName (e-PCR)
- UniSTS:480623

NoName (e-PCR)
- UniSTS:482940

RH93403 (e-PCR)
- UniSTS:83840

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine binding	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	TAS Traceable Author Statement more info	PubMed
enables transmembrane signaling receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables tumor necrosis factor receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables tumor necrosis factor receptor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
involved_in adaptive immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to zinc ion starvation	IEA Inferred from Electronic Annotation more info
involved_in circadian temperature homeostasis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in lymph node development	IBA Inferred from Biological aspect of Ancestor more info
involved_in mammary gland alveolus development	IEA Inferred from Electronic Annotation more info
involved_in monocyte chemotaxis	NAS Non-traceable Author Statement more info	PubMed
involved_in multinuclear osteoclast differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in ossification	IBA Inferred from Biological aspect of Ancestor more info
involved_in osteoclast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of JUN kinase activity	IMP Inferred from Mutant Phenotype 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 NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of bone resorption	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell population proliferation	TAS Traceable Author Statement 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 osteoclast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to insulin	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-1	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in response to lipopolysaccharide	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
involved_in response to tumor necrosis factor	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in tumor necrosis factor-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in tumor necrosis factor-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tumor necrosis factor-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tumor necrosis factor receptor superfamily member 11A

Names: Paget disease of bone 2; TRANCE receptor; familial expansile osteolysis; 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)

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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

NG_008098.1 RefSeqGene

Range

4973..67396

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_194

mRNA and Protein(s)

NM_001270949.2 → NP_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

UniProtKB/Swiss-Prot

Q9Y6Q6

Conserved Domains (1) summary

cd13411
Location:33 → 195

TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
NM_001270950.2 → NP_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

UniProtKB/Swiss-Prot

Q9Y6Q6

Conserved Domains (2) summary

cd13411
Location:33 → 195

TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

pfam05454
Location:173 → 258

DAG1; Dystroglycan (Dystrophin-associated glycoprotein 1)
NM_001270951.2 → NP_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:33 → 195

TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
NM_001278268.2 → NP_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:33 → 181

TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
NM_003839.4 → NP_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

I4EC36, I4EC38, I4EC39, I7JE63, N0GVH0, Q59EP9, Q9Y6Q6

Related

ENSP00000465500.1, ENST00000586569.3

Conserved Domains (1) summary

cd13411
Location:33 → 195

TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000018.10 Reference GRCh38.p14 Primary Assembly

Range

62325310..62391288

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526245.3 → XP_011524547.1 tumor necrosis factor receptor superfamily member 11A isoform X2

Conserved Domains (1) summary

cl22855
Location:109 → 159

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
XM_011526244.3 → XP_011524546.1 tumor necrosis factor receptor superfamily member 11A isoform X1

Conserved Domains (1) summary

cd13411
Location:33 → 200

TNFRSF11A; Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK)
XM_017026064.2 → XP_016881553.1 tumor necrosis factor receptor superfamily member 11A isoform X2

Conserved Domains (1) summary

cl22855
Location:109 → 159

TNFRSF; Tumor necrosis factor receptor superfamily (TNFRSF)
XM_017026065.2 → XP_016881554.1 tumor necrosis factor receptor superfamily member 11A isoform X3
XM_017026066.2 → XP_016881555.1 tumor necrosis factor receptor superfamily member 11A isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060942.1 Alternate T2T-CHM13v2.0

Range

62528176..62594158

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054319318.1 → XP_054175293.1 tumor necrosis factor receptor superfamily member 11A isoform X2
XM_054319316.1 → XP_054175291.1 tumor necrosis factor receptor superfamily member 11A isoform X1
XM_054319317.1 → XP_054175292.1 tumor necrosis factor receptor superfamily member 11A isoform X2
XM_054319319.1 → XP_054175294.1 tumor necrosis factor receptor superfamily member 11A isoform X5
XM_054319320.1 → XP_054175295.1 tumor necrosis factor receptor superfamily member 11A isoform X3
XM_054319321.1 → XP_054175296.1 tumor necrosis factor receptor superfamily member 11A isoform X4