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

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; AllianceGenome:HGNC:11926
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: mouse all
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Genomic context

Location:: 13q14.11

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (42562736..42608013)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (41782656..41827951)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (43136872..43182149)

Chromosome 13 - NC_000013.11 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.
Genetic Variants of the Receptor Activator Nuclear of kappaB Ligand Gene Increase the Risk of Rheumatoid Arthritis in a Mexican Mestizo Population: A Case-Control Study.
Title: Genetic Variants of the Receptor Activator Nuclear of κB Ligand Gene Increase the Risk of Rheumatoid Arthritis in a Mexican Mestizo Population: A Case-Control Study.
Accumulation of gammadeltaT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-kappaB.
Title: Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.
Overexpression of TNFSF11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers in lung adenocarcinoma.
Title: Overexpression of TNFSF11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers in lung adenocarcinoma.
Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.
Title: Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.
RANK/RANKL axis promotes migration, invasion, and metastasis of osteosarcoma via activating NF-kappaB pathway.
Title: RANK/RANKL axis promotes migration, invasion, and metastasis of osteosarcoma via activating NF-κB pathway.
The Notch1 signaling pathway directly modulates the human RANKL-induced osteoclastogenesis.
Title: The Notch1 signaling pathway directly modulates the human RANKL-induced osteoclastogenesis.
RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes.
Title: RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes.
Pulling rank with RNA: RANKL promotes the association of PGC-1beta/RNA complexes with NCoR/HDAC3 to activate gene expression in osteoclasts.
Title: Pulling rank with RNA: RANKL promotes the association of PGC-1β/RNA complexes with NCoR/HDAC3 to activate gene expression in osteoclasts.
[RANKL and periodontitis].
Title: [RANKL and periodontitis].

Submit: New GeneRIF Correction See all GeneRIFs (668)

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 2 MedGen: C1850126 OMIM: 259710 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

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

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:482057

RH102002 (e-PCR)
- UniSTS:96336

D13S325 (e-PCR), detects polymorphism
- UniSTS:67237

NoName (e-PCR)
- UniSTS:490453

TNFSF11_2446 (e-PCR)
- UniSTS:281064

SHGC-132244 (e-PCR)
- UniSTS:170728

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
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 JNK cascade	IEA Inferred from Electronic Annotation more info
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 cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor 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 negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
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 phosphatidylinositol 3-kinase/protein kinase B signal transduction	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	IDA Inferred from Direct Assay more info	PubMed
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 canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of corticotropin-releasing hormone secretion	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
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	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of osteoclast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	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 tooth eruption	IEA Inferred from Electronic Annotation more info
involved_in tumor necrosis factor-mediated signaling pathway	IDA Inferred from Direct Assay 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 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
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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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)

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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_008990.1 RefSeqGene

Range

16417..50278

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003701.4 → NP_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

O14723, O14788, Q96Q17, Q9P2Q3

UniProtKB/TrEMBL

Q5T9Y4

Related

ENSP00000381775.3, ENST00000398795.7

Conserved Domains (1) summary

pfam00229
Location:185 → 313

TNF; TNF(tumor Necrosis Factor) family
NM_033012.4 → NP_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/TrEMBL

Q54A98

Related

ENSP00000351347.2, ENST00000358545.6

Conserved Domains (1) summary

pfam00229
Location:112 → 240

TNF; TNF(tumor Necrosis Factor) family

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_000013.11 Reference GRCh38.p14 Primary Assembly

Range

42562736..42608013

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047430707.1 → XP_047286663.1 tumor necrosis factor ligand superfamily member 11 isoform X2

UniProtKB/TrEMBL

Q54A98
XM_011535280.3 → XP_011533582.1 tumor necrosis factor ligand superfamily member 11 isoform X2

See identical proteins and their annotated locations for XP_011533582.1

UniProtKB/TrEMBL

Q54A98

Conserved Domains (1) summary

pfam00229
Location:112 → 240

TNF; TNF(tumor Necrosis Factor) family
XM_017020803.3 → XP_016876292.1 tumor necrosis factor ligand superfamily member 11 isoform X2

UniProtKB/TrEMBL

Q54A98

Conserved Domains (1) summary

pfam00229
Location:112 → 240

TNF; TNF(tumor Necrosis Factor) family
XM_017020802.2 → XP_016876291.1 tumor necrosis factor ligand superfamily member 11 isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060937.1 Alternate T2T-CHM13v2.0

Range

41782656..41827951

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054375076.1 → XP_054231051.1 tumor necrosis factor ligand superfamily member 11 isoform X2

UniProtKB/TrEMBL

Q54A98
XM_054375077.1 → XP_054231052.1 tumor necrosis factor ligand superfamily member 11 isoform X2

UniProtKB/TrEMBL

Q54A98
XM_054375078.1 → XP_054231053.1 tumor necrosis factor ligand superfamily member 11 isoform X2

UniProtKB/TrEMBL

Q54A98
XM_054375075.1 → XP_054231050.1 tumor necrosis factor ligand superfamily member 11 isoform X1