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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TNFSF11 Gene

protein-coding GIFtS: 69
GCID: GC13P043136

tumor necrosis factor (ligand) superfamily, member 11

Explore 130 diseases affiliated with
TNFSF11 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Tumor Necrosis Factor (Ligand) Superfamily, Member 11¹ ²		Receptor Activator Of Nuclear Factor Kappa-B Ligand² ³
OPGL¹ ² ³ ⁵		TNF-Related Activation-Induced Cytokine² ³
TRANCE¹ ² ³ ⁵		OPTB2² ⁵
ODF¹ ² ³		HRANKL2¹
RANKL¹ ² ³		Receptor Activator Of Nuclear Factor Kappa B Ligand²
CD254¹ ²		SOdf¹
Osteoclast Differentiation Factor² ³		Tumor Necrosis Factor Ligand Superfamily Member 11²
Osteoprotegerin Ligand² ³		CD254 Antigen³

External Ids:	HGNC: 11926¹	Entrez Gene: 8600²	Ensembl: ENSG00000120659⁷	OMIM: 602642⁵	UniProtKB: O14788³

Export aliases for TNFSF11 gene to outside databases

Previous GC identifers: GC13P041146 GC13P037132 GC13P042073 GC13P040934 GC13P040943 GC13P042034 GC13P023940

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TNFSF11:

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)

UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788

Function: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor.

Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of

interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune

response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy

Gene Wiki entry for TNFSF11 (RANKL)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000013.10 NC_018924.1 NT_024524.14

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TNFSF11 gene promoter:
STAT1 FOXO4 STAT1beta STAT3 STAT1alpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): TNFSF11 promoter sequence

Search SABiosciences Chromatin IP Primers for TNFSF11

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TNFSF11

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 13q14 Ensembl cytogenetic band: 13q14.11 HGNC cytogenetic band: 13q14

TNFSF11 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TNFSF11 gene location

GeneLoc information about chromosome 13 GeneLoc Exon Structure

GeneLoc location for GC13P043136: view genomic region (about GC identifiers)

Start:	43,136,872 bp from pter	End:	43,182,149 bp from pter
Size:	45,278 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788 (See protein sequence)

Recommended Name: Tumor necrosis factor ligand superfamily member 11

Size: 317 amino acids; 35478 Da

Subunit: Homotrimer (Probable). Interacts with TNFRSF11B

Subcellular location: Isoform 1: Cell membrane; Single-pass type II membrane protein

Subcellular location: Isoform 3: Cell membrane; Single-pass type II membrane protein

Subcellular location: Isoform 2: Cytoplasm (By similarity)

Subcellular location: Tumor necrosis factor ligand superfamily member 11, soluble form: Secreted (By similarity)

1 PDB 3D structure from and Proteopedia for TNFSF11:

3URF (3D)

Secondary accessions: O14723 Q96Q17 Q9P2Q3

Alternative splicing: 3 isoforms: O14788-1 O14788-2 O14788-3

Explore the universe of human proteins at neXtProt for TNFSF11: NX_O14788

Post-translational modifications:

The soluble form of isoform 1 derives from the membrane form by proteolytic processing (By similarity). The cleavage

may be catalyzed by ADAM17¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O14788

TNFSF11 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_003692.1 NP_143026.1

ENSEMBL proteins:

ENSP00000351347 ENSP00000239849 ENSP00000384042 ENSP00000381775 ENSP00000444913

Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant TNFSF11 Protein
	R&D Systems Recombinant & Natural Proteins for TNFSF11 (TRANCE/TNFSF11/RANK L)
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	OriGene Purified Protein: TNFSF11 OriGene Protein Over-expression Lysate (see all 2): TNFSF11 OriGene Custom Protein Services for TNFSF11
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	Novus Biologicals TNFSF11 Proteins Novus Biologicals TNFSF11 Lysates
	Sino Biological Recombinant Protein for TNFSF11
	ProSpec Recombinant Protein for TNFSF11
	Browse Proteins at Uscn

Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	NAS	10708588
GO:0005615	extracellular space	IEA	--
GO:0005622	intracellular	--	--
GO:0005737	cytoplasm	IEA	--
GO:0005887	integral to plasma membrane	NAS	9312132

TNFSF11 for ontologies About GeneDecksing

TNFSF11 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TNFSF11
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	OriGene Antibodies (see all 3): TNFSF11 OriGene Custom Antibody Services for TNFSF11
	GenScript Custom Superior Antibodies Services for TNFSF11
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	Abcam antibodies for TNFSF11
	Browse Antibodies at Uscn
	ThermoFisher Antibodies for TNFSF11

Assay Products for TNFSF11:

	EMD Millipore Kits and Assays for the Analysis of TNFSF11
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for TNFSF11 (TRANCE/TNFSF11/RANK L) (see all)
	GenScript Custom Assay Services for TNFSF11
	Enzo Life Sciences assays for TNFSF11
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TNFSF11 for domains About GeneDecksing

3 InterPro domains/families:

IPR006052 TNF

IPR008983 Tumour_necrosis_fac-like_dom

IPR017355 TNF_ligand_10/11

Graphical View of Domain Structure for InterPro Entry O14788

ProtoNet protein and cluster: O14788

1 Blocks protein family: IPB006052 Tumor Necrosis Factor

UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788

Similarity: Belongs to the tumor necrosis factor family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788

Function: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor.

Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of

interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune

response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy

Induction: Up-regulated by T-cell receptor stimulation

Genatlas biochemistry entry for TNFSF11:

tumor necrosis factor superfamily,member 11 TNFRSF11A (RANK) and OPG (osteprogerin ligand),localized in T cells bone

marrow stromal cells,hypertrophic chondrocyte,stimulated by IL1B and TNFRSF11B,expressed in bone,

brain,heart,kidney,skeletal muscle,skin,cooperating with prostaglandin,mediating osteoclastognesis and bone loss

through systemic activation of T cells,regulating lymph node organogenesis lymphocyte development and interactions

between T cells and dendritic cells,activating the antiapoptotic serine threonine kinase AKT/PKB through a signal

complex involving TRAF6 and SRC

Summary:

During embryonic development, TNFSF11 as signaling molecule

affects the following cells: Osteoclasts in Bone Marrow

miRNA Products:		miRTarBase miRNAs that target TNFSF11: hsa-mir-18a (MIRT004387)

		OriGene 3'-UTR Clone (see all 2): TNFSF11 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TNFSF11
		8/26 QIAGEN miScript miRNA Assays for microRNAs that regulate TNFSF11 (see all 26):
		hsa-miR-323-3p hsa-miR-520d-5p hsa-miR-106a hsa-miR-657 hsa-let-7a-2* hsa-miR-488 hsa-miR-519a hsa-miR-144

		SwitchGear 3'UTR luciferase reporter plasmid: TNFSF11 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TNFSF11 (see all 7) OriGene shRNA RFP: TNFSF11 OriGene siRNA: TNFSF11
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Gene Editing
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DNA2.0 Custom Protein Engineering Service for TNFSF11

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		GenScript: all cDNA clones in your preferred vector (see all 2): TNFSF11 (NM_003701)
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TNFSF11

Gene Ontology (GO): 5 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004872	receptor activity	--	--
GO:0005125	cytokine activity	NAS	9568710
GO:0005164	tumor necrosis factor receptor binding	NAS	9367155
GO:0005515	protein binding	--	--
GO:0032813	tumor necrosis factor receptor superfamily binding	IC	19940926

TNFSF11 for ontologies           About GeneDecksing

Animal Models:
     Mouse knock-outs for TNFSF11: Tnfsf11^tm1Ywc Tnfsf11^tm1Pngr Tnfsf11^tm1.2Htaka
     12 MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Tnfsf11):

cellular	craniofacial	endocrine/exocrine gland	growth/size	hematopoietic system
homeostasis/metabolism	immune system	integument	limbs/digits/tail	mortality/aging
reproductive system	skeleton

TNFSF11 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/20 super-pathways (see all 20) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

PEDF Induced Signaling

8/9 pathways (see all 9)
PEDF Induced Signaling	1.00	RAR-Gamma-RXR-Alpha Degradation	0.54
MIF Mediated Glucocorticoid Regulation	0.73	STAT3 Pathway	0.47
MIF Regulation of Innate Immune Cells	0.71	Endothelin-1 Signaling Pathway	0.44
IL-6 Pathway	0.61	Cytokine-cytokine receptor interaction	0.26

Rho Family GTPases

	Rho Family GTPases	1.00			Molecular Mechanisms of Cancer	0.51
	ERK Signaling	0.61

TRAF Pathway

	TRAF Pathway	1.00			TNF Superfamily - Human Ligand-Receptor Interactions & their Associated Functions	0.08
	TNF Superfamily Pathway	0.42

BAFF in B-Cell Signaling

	RANK Signaling in Osteoclasts	0.45			RANKL/RANK Signaling Pathway	0.24
	RANK Pathway	0.29

Transcription_Role of VDR in regulation of genes involved in osteoporosis

Transcription_Role of VDR in regulation of genes involved in osteoporosis

1.00

Transcription Role of VDR in regulation of genes involved in osteoporosis

0.80

Pathway sources
See GeneCards unified pathways
Show all pathways

5 EMD Millipore Pathways for TNFSF11

	Development Hedgehog and PTH signaling pathways in bone and cartilage development
	Selected targets of Oct-3/4
	Transcription Role of VDR in regulation of genes involved in osteoporosis
	Selected targets of GCR-alpha
	Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway

1 R&D Systems Pathway for TNFSF11

TNF Superfamily - Human Ligand-Receptor Interactions & their Associated Functions

5/20 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for TNFSF11 (see all 20)

	TRAF Pathway
	Endothelin-1 Signaling Pathway
	Molecular Mechanisms of Cancer
	Antioxidant Action of Vitamin-C
	TRAIL Pathway

3 Cell Signaling Technology (CST) Pathways for TNFSF11

	Apoptosis and Autophagy
	Lymphocyte Signaling
	NF-kappaB Signaling

3 GeneGo (Thomson Reuters) Pathways for TNFSF11

	Development Hedgehog and PTH signaling pathways in bone and cartilage development
	Transcription Role of VDR in regulation of genes involved in osteoporosis
	Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway

4 BioSystems Pathways for TNFSF11

	RANKL/RANK Signaling Pathway
	Osteoclast Signaling
	Osteoblast Signaling
	IL6-mediated signaling events

3 Kegg Pathways (Kegg details for TNFSF11):

	Cytokine-cytokine receptor interaction
	Osteoclast differentiation
	Rheumatoid arthritis

TNFSF11 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TNFSF11

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/39 Interacting proteins for TNFSF11 (O14788^{2, 3} ENSP00000239849⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 39)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
BBS10	Q8TAM1²^,³	MINT-8274632 I2D: score=2
DDAH2	O95865²^,³	MINT-8274654 I2D: score=2
EEF1A1	P68104²^,³	MINT-8274665 I2D: score=2
EZH2	Q15910²^,³	MINT-8274676 I2D: score=2
KIAA1377	Q9P2H0²^,³	MINT-8274687 I2D: score=2

About this table

Gene Ontology (GO): 5/33 biological process terms (GO ID links to tree view) (see all 33): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001503	ossification	IEA	--
GO:0002548	monocyte chemotaxis	IDA	15248232
GO:0006950	response to stress	--	--
GO:0006955	immune response	NAS	9312132
GO:0007257	activation of JUN kinase activity	IEA	--

TNFSF11 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TNFSF11 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for TNFSF11

Browse Tocris compounds for TNFSF11

1 DrugBank Compound for TNFSF11 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Lenalidomide	CC-5013 (see all 3)	191732-72-6	target	inhibitor	17369076 19370685

10/99 Novoseek chemical compound relationships for TNFSF11 gene (see all 99) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
denosumab	93.7	88	19016581 (5), 19590040 (3), 19092832 (3), 19404943 (2) (see all 58)
tartrate	65.2	6	14751235 (1), 18565244 (1), 19057837 (1), 16948499 (1) (see all 6)
1,25 dihydroxy vitamin d3	61.3	13	10913332 (3), 19464673 (2), 12364326 (1), 17053039 (1) (see all 10)
zoledronic acid	61.2	21	14753746 (5), 19670154 (4), 18289304 (2), 16938523 (1) (see all 8)
hcc-1	60.9	3	12773123 (3)
pge2	52.4	79	20112374 (5), 15068113 (5), 17951042 (5), 17559635 (4) (see all 31)
calcitriol	50.7	25	19073256 (2), 12421995 (1), 14693199 (1), 19732857 (1) (see all 14)
mip 1alpha	49.9	5	16211583 (2), 12965277 (1), 17506059 (1)
risedronate	49.3	9	19301089 (3), 17967134 (2), 18275008 (2), 15777635 (1) (see all 5)
alendronate	48.8	6	19574937 (3), 17966399 (1), 19092832 (1)

Search CenterWatch for drugs/clinical trials and news about TNFSF11 / TNF11

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TNFSF11 gene (2 alternative transcripts):

NM_003701.3 NM_033012.3

Unigene Cluster for TNFSF11:

Tumor necrosis factor (ligand) superfamily, member 11

Hs.333791 [show with all ESTs]

Unigene Representative Sequence: NM_033012

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000358545 ENST00000239849 ENST00000405262(uc001uyt.2) ENST00000398795(uc001uyu.2)

ENST00000544862

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		8/26 QIAGEN miScript miRNA Assays for microRNAs that regulate TNFSF11 (see all 26):
		hsa-miR-323-3p hsa-miR-520d-5p hsa-miR-106a hsa-miR-657 hsa-let-7a-2* hsa-miR-488 hsa-miR-519a hsa-miR-144

		SwitchGear 3'UTR luciferase reporter plasmid: TNFSF11 3' UTR sequence

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		GenScript: all cDNA clones in your preferred vector (see all 2): TNFSF11 (NM_003701)
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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TNFSF11
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TNFSF11

Additional cDNA sequence:

AB037599.1 AB061227.1 AB064268.1 AB064269.1 AB064270.1 AF013171.1 AF019047.1 AF053712.1

BC040889.1 BC074823.2 BC074890.2 BC117286.1 BC117288.1

4 DOTS entries:

DT.100021499 DT.208116 DT.91692886 DT.95154602

23 AceView cDNA sequences:

AB064269 AB064268 BC040889 NM_033012 BC074890 AV653073 BC074823 AB064270

AB061227 AF019047 BM893658 AA504450 AB037599 NM_003701 AF013171 AA504211

BX105834 BQ007726 AF053712 BM966907 BM564083 AI808584 CK823311

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TNFSF11 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CTGGAACCTG

About this image

TNFSF11 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Bone

Zeugopod Periosteum

Bone

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See TNFSF11 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TNFSF11

SOURCE GeneReport for Unigene cluster: Hs.333791

UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788

Tissue specificity: Highest in the peripheral lymph nodes, weak in spleen, peripheral blood Leukocytes, bone marrow,

heart, placenta, skeletal muscle, stomach and thyroid

SABiosciences Expression via Pathway-Focused PCR Arrays including TNFSF11 (see all 10):

Osteogenesis in human mouse rat

Inflammasomes in human mouse rat

Inflammatory Response & Autoimmunity 384HT in human mouse rat

Antigen Presenting Cells in human mouse rat

Inflammatory Cytokines & Receptors in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for TNFSF11 gene from 3/11 species (see all 11) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	TNFSF11¹	tumor necrosis factor (ligand) superfamily, member more	69.12(n) 62.45(a)		428067 NM_001083361.1 NP_001076830.1
lizard (Anolis carolinensis)	Reptilia	TNFSF11⁶	--	63(a)	1 ↔ 1	3(70130506-70152992)
zebrafish (Danio rerio)	Actinopterygii	tnfsf11⁶ tnfsf10l4⁶	tumor necrosis factor (ligand) superfamily, member... tumor necrosis factor (ligand) superfamily, member...	25(a) 19(a)	1 ↔ 1 possible ortholog	9(18539651-18558869) 5(24363303-24366870)

ENSEMBL Gene Tree for TNFSF11 (if available)
TreeFam Gene Tree for TNFSF11 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for TNFSF11 gene

TNFSF10²

1 SIMAP similar gene for TNFSF11 using alignment to 2 protein entries: TNF11_HUMAN (see all proteins):

hRANKL 3

TNFSF11 for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for TNFSF11
PGOHUM00000239976

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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SNP ID	Valid	Clinical significance	Chr 13 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs74803005^1,2	F,	--	23938661(+)	`TACATG/ATGTAT`	1	--	us2k¹		1		WA	118
rs76666379^1,2	F,	--	23938814(+)	`TAAAGA/CGCCTA`	1	--	us2k¹		1		NA	120
rs61959536^1,2	C,	--	23938845(+)	`AGGTGA/GTGAGA`	1	--	us2k¹		2		NA	122
rs112307654^1,2	C,	--	23939014(+)	`GGAGGT/CGAAGT`	1	--	us2k¹		2		WA CSA	3
rs76081955^1,2	C,	--	23939018(+)	`GCGAAG/ATTGGG`	1	--	us2k¹		2		WA	120
rs79908842^1,2	C,F,	--	23940001(+)	`TGTTAT/CATGTG`	1	--	us2k¹		2		NA EA	240
rs74521129^1,2		--	23940080(+)	`AAAGTC/ATTTTC`	1	--	us2k¹		1		NA	120
rs75361912^1,2	F,	--	23940144(+)	`CTAATT/GACATT`	1	--	us2k¹		1		WA	118
rs200090640^1,2	C	--	23940300(-)	`GGCTTG/TATTAC`	1	--	us2k¹		0	--	--	--	--
rs116485194^1,2	C,F,	--	23940534(+)	`TGTACC/GAGGGA`	1	--	ut5¹		1		WA	118

HapMap Linkage Disequilibrium report for TNFSF11 (43136872 - 43182149 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for TNFSF11
1 CNV: 7013
Human Gene Mutation Database (HGMD): TNFSF11

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TNFSF11 for disorders           About GeneDecksing

OMIM gene information: 602642
OMIM disorders: 259710
UniProtKB/Swiss-Prot: TNF11_HUMAN, O14788

Defects in TNFSF11 are the cause of osteopetrosis autosomal recessive type 2 (OPTB2) [MIM:259710]; also known

as osteoclast-poor osteopetrosis. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due

to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form

occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood.

Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts.

OPTB2 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development

20/130 diseases for TNFSF11 (see all 130): About MalaCards

osteopetrosis osteopetrosis autosomal recessive 2 monoclonal gammopathy of undetermined significance pigmented villonodular synovitis

periapical granuloma multicentric reticulohistiocytosis villonodular synovitis middle ear cholesteatoma

osteopenia/osteoporosis paget disease, juvenile osteoporosis, postmenopausal root resorption

beta thalassemia chronic apical periodontitis bone resorption disease icos deficiency

acute myocardial infarction humoral hypercalcemia of malignancy mammary paget's disease giant cell tumor

6 diseases from the University of Copenhagen DISEASES database for TNFSF11:

Osteoporosis Periodontal disease Arthritis Osteopetrosis

Multiple myeloma Giant cell tumor

10/93 Novoseek disease relationships for TNFSF11 gene (see all 93) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
bone destruction	90.1	70	16144909 (4), 12469211 (3), 10995794 (2), 12223101 (2) (see all 48)
bone diseases	86.4	85	12424190 (3), 12684416 (3), 19185505 (2), 15205949 (2) (see all 60)
osteolysis	85.3	98	17683568 (5), 19590968 (5), 20215062 (4), 19502684 (3) (see all 56)
bone loss	85	114	12707582 (3), 12379618 (3), 14690142 (2), 16806459 (2) (see all 71)
osteolytic	84.9	57	11870668 (3), 15044512 (2), 12684416 (2), 12665629 (2) (see all 40)
osteoporosis	82.6	80	19229472 (3), 19352306 (3), 15068494 (2), 17634142 (2) (see all 60)
paget disease, juvenile	76.2	2	16491292 (1), 17174136 (1)
osteoporosis postmenopausal	75.7	28	17895323 (2), 18375161 (2), 15068494 (1), 17684931 (1) (see all 23)
rheumatoid arthritis	75	84	16301197 (2), 15476205 (2), 18576301 (2), 12429533 (2) (see all 64)
bone metastases	72.6	39	19360288 (3), 17195907 (3), 19344283 (3), 18685421 (3) (see all 24)

Genetic Association Database (GAD): TNFSF11
Human Genome Epidemiology (HuGE) Navigator: TNFSF11 (39 documents)

Export disorders for TNFSF11 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for TNFSF11 gene, integrated from 9 sources (see all 1379):
(articles sorted by number of sources associating them with TNFSF11)

Utopia: connect your pdf to the dynamic
world of online information

TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. (PubMed id 9312132)^{1, 2, 3, 9} Wong B.R....Choi Y. (1997)
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. (PubMed id 9367155)^{1, 2, 3, 9} Anderson D.M....Galibert L. (1997)
Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men. (PubMed id 16249885)^{1, 4, 9} Hsu Y.H....Xu X. (2006)
Interaction between RANKL and HLA-DRB1 genotypes may contribute to younger age at onset of seropositive rheumatoid arthritis in an inception cohort. (PubMed id 15476205)^{1, 4, 9} Wu H....Tsao B.P. (2004)
Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. (PubMed id 17632511)^{1, 2, 9} Sobacchi C.... Helfrich M.H. (2007)
Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation. (PubMed id 10708588)^{1, 2, 9} Nagai M.... Sato N. (2000)
Crystal structure of human RANKL complexed with its de coy receptor osteoprotegerin. (PubMed id 22664871)^{1, 2} Luan X....Wang X. (2012)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. (PubMed id 9568710)^{1, 2} Lacey D.L....Boyle W.J. (1998)
Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: influence of osteotropic factors. (PubMed id 18539107)^{1, 9} Tat S.K....Martel-Pelletier J. (2008)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 8600	HGNC: 11926	AceView: TNFSF11	Ensembl:ENSG00000120659	euGenes: HUgn8600
ECgene: TNFSF11	Kegg: 8600	H-InvDB: TNFSF11

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for TNFSF11	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TNFSF11	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for TNFSF11 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TNFSF11 gene:
Search GeneIP for patents involving TNFSF11

GeneCards and IP:
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TNFSF11 Gene

tumor necrosis factor (ligand) superfamily, member 11

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Spondylitis Ankylosing
Osteopetrosis
Gingivitis
MICROPHTHALMIA
Osteomyelitis
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Acute myocardial infarction
FAMILIAL EXPANSILE OSTEOLYSIS
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TNFSF11 Gene

tumor necrosis factor (ligand) superfamily, member 11

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