TNFRSF11A

Summary

TNFRSF11A (TNF receptor superfamily member 11a, HGNC:11908) is a protein-coding gene on chromosome 18q21.33, encoding Tumor necrosis factor receptor superfamily member 11A (Q9Y6Q6). Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis.

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.

Source: NCBI Gene 8792 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive osteopetrosis 7 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 33
• Clinical variants (ClinVar): 759 total — 17 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 88
• MANE Select transcript: NM_003839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11908
Approved symbol	TNFRSF11A
Name	TNF receptor superfamily member 11a
Location	18q21.33
Locus type	gene with protein product
Status	Approved
Aliases	RANK, CD265, FEO, ODFR, TRANCE-R
Ensembl gene	ENSG00000141655
Ensembl biotype	protein_coding
OMIM	603499
Entrez	8792

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 retained_intron

ENST00000269485, ENST00000586569, ENST00000587697, ENST00000592013, ENST00000903841, ENST00000903842, ENST00000903843, ENST00000903844, ENST00000938972, ENST00000938973

RefSeq mRNA: 5 — MANE Select: NM_003839 NM_001270949, NM_001270950, NM_001270951, NM_001278268, NM_003839

CCDS: CCDS11980, CCDS59324

Canonical transcript exons

ENST00000586569 — 10 exons

Exon	Start	End
ENSE00000950287	62366708	62366760
ENSE00000950400	62349812	62349937
ENSE00000950401	62354391	62354534
ENSE00000950402	62358248	62358341
ENSE00000950428	62359955	62360049
ENSE00001269605	62368701	62369484
ENSE00001269619	62361680	62361793
ENSE00001269681	62348168	62348249
ENSE00001315729	62325310	62325427
ENSE00002920262	62384751	62391288

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 96.56.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9165 / max 152.6582, expressed in 737 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170516	1.8799	535
170517	0.5495	189
170514	0.2087	102
170515	0.1779	69
170513	0.1004	34

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	96.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.45	gold quality
jejunal mucosa	UBERON:0000399	95.38	gold quality
colonic mucosa	UBERON:0000317	95.22	gold quality
rectum	UBERON:0001052	88.99	gold quality
duodenum	UBERON:0002114	88.89	gold quality
ileal mucosa	UBERON:0000331	83.29	silver quality
saliva-secreting gland	UBERON:0001044	82.46	gold quality
mucosa of transverse colon	UBERON:0004991	82.02	gold quality
pancreatic ductal cell	CL:0002079	80.84	silver quality
gall bladder	UBERON:0002110	80.70	gold quality
colonic epithelium	UBERON:0000397	80.29	gold quality
islet of Langerhans	UBERON:0000006	80.02	gold quality
minor salivary gland	UBERON:0001830	79.41	gold quality
transverse colon	UBERON:0001157	78.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.37	gold quality
small intestine	UBERON:0002108	78.15	gold quality
mouth mucosa	UBERON:0003729	77.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.76	gold quality
intestine	UBERON:0000160	75.96	gold quality
jejunum	UBERON:0002115	75.66	gold quality
tibia	UBERON:0000979	75.42	gold quality
palpebral conjunctiva	UBERON:0001812	75.19	gold quality
large intestine	UBERON:0000059	75.17	gold quality
seminal vesicle	UBERON:0000998	75.14	gold quality
amniotic fluid	UBERON:0000173	74.75	gold quality
vermiform appendix	UBERON:0001154	74.66	gold quality
colon	UBERON:0001155	74.52	gold quality
pituitary gland	UBERON:0000007	74.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.09	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	17.48
E-ANND-3	yes	6.62
E-MTAB-7303	no	196.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, ARID1A, ATF2, ATF4, BCL6, CEBPB, CNOT3, CTBP2, DLX4, DNMT3B, EGR1, ESR1, ESR2, EZH2, FOXA2, FOXC1, FOXO3, GCM1, GRHL3, HMGA2, ID1, IRF3, IRF6, JUN, KAT5, KDM5A, KLF12, KLF2, KLF8, MITF, MTA1, MXD1, MYC, MYOG, NCOA3, NEUROD1, NFATC1, NFKB1, NFKB

miRNA regulators (miRDB)

74 targeting TNFRSF11A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-7152-5P	99.60	69.33	2094

Literature-anchored findings (GeneRIF, showing 40)

• Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication (84dup15) in TNFRSF11A encoding RANK. (PMID:11771666)
• immunohistochemical localization of this protein and its ligand in deciduous teeth (PMID:12043011)
• MIP-1alpha and MIP-1beta induce expression of RANK ligand by stromal cells, thereby stimulating osteoclast differentiation of preosteoclastic cells. (PMID:12200385)
• TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB. (PMID:12296995)
• Analysis of a large Spanish kindred confirms that exon 1 contains an insertional mutation in the RANK gene. (PMID:12362049)
• Long-lived immature dendritic cells mediated by TRANCE-RANK interaction (PMID:12393586)
• a tandem duplication in exon 1 of the TNFRSF11A gene may have a role in familial expansile osteolysis (PMID:12568416)
• associated with external apical root resorption (PMID:12709501)
• the 75dup27 mutation causes a Paget’s disease of bone-like phenotype (PMID:12929927)
• transforming growth factor-beta promotes osteoclastogenesis in monocytes by stimulation of the p38 mitogen activated protein kinase but continuous exposure abrogates osteoclastogenesis by down-regulation of receptor activator of NF-KB(RANK) expression (PMID:12933809)
• These data suggest that RANK is expressed by monocytes whose activation by RANKL stimulates directed migration involving phosphatidylinositol 3-kinase, phosphodiesterase, and Src kinases. (PMID:15248232)
• RANK is expressed in bone marrow stroma cells & endothelial cells but not myeloma cells. It is involed in IL-6 & IL-11 secretion. (PMID:15377473)
• Review. The RANKL/RANK/OPG system may mediate links between the vascular, skeletal, & immune systems and play a central role in regulating the vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease. (PMID:15564564)
• disruption of the RANKL-RANK axis with OPG inhibited tumor-induced osteoclastogenesis and decreased bone cancer pain. (PMID:15615497)
• Involvement of RANK/RANKL in dendritic cell-T cell interactions during inflammatory process. RANK expression appears to be limited to sites of immune reaction, both in synovium and in lymph nodes. (PMID:16052586)
• PU.1 regulates RANK gene transcription; this may represent one of the key roles of PU.1 in osteoclast differentiation (PMID:16083856)
• OPG dimer formation is required for the mechanism of inhibition of the RANK-L/RANK receptor interaction (PMID:16215261)
• We review the etiology of inflammatory bone loss, the RANK/RANK-ligand/OPG pathway, and the clinical development of anti-RANK-ligand therapy. (PMID:16240334)
• By upregulating IL-8, the RANKL/RANK system may contribute to the pathogenesis of B chronic lymphocytic leukemia. (PMID:16270354)
• a functional RANK expressed on osteosarcoma cells (PMID:16328004)
• Expression of RANK-Fc by genetically modified Mesenchymal stem cells may be a feasible option for the prevention of bone loss induced by ovariectomy. (PMID:16556708)
• results suggest that +34863G > A and +35928insdelC polymorphisms in RANK are possible genetic factors for low Bone mineral density in postmenopausal women (PMID:17115234)
• This review describes the most recent knowledge on the OPG-receptor activator of nuclear factor-kappaB (RANK)-RANK ligand (RANKL) triad and its involvement in bone oncology. (PMID:17288531)
• Although the mutation in the Iranian and four of the previously described FEO pedigrees was the same, haplotypes based on the intragenic SNPs suggest that the mutations do not share a common descent. (PMID:17447113)
• A major haplotype in block 5 of Tumor Necrosis Factor receptor superfamily member 11a (RANK) was significantly associated with higher stature in Caucasians. (PMID:17546619)
• The expression levels of RANKL and RANK were markedly increased in the perimatrix of cholesteatoma. (PMID:17580719)
• Review highlights the receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/osteoprotegerin (OPG) system and its role in the regulation of bone resorption. (PMID:17634140)
• RANK contributes to osteoclastic bone resoption in RA patients. (PMID:17876645)
• RANK/RANKL/OPG system mediates the effects of calciotropic hormones and, consequently, alterations in their ratio are key in the development of several clinical conditions–REVIEW (PMID:17895323)
• The OPG/RANKL/RANK system constitutes the important element of controlling the number of active osteoclasts by the osteoblasts. (PMID:17966895)
• cDNA microarray and quantitative RT-PCR analyses demonstrate that RANK-positive osteosarcoma cells are the target of RANKL as well as osteoclasts/osteoclast precursors. (PMID:17982618)
• RANK is expressed on prostate cancer cells and promotes invasion in a RANKL-dependent manner (PMID:18008334)
• differences in the RANK, RANKL, and OPG expression in odontogenic epithelial tumors…could contribute to the differential bone/tooth resorption activity in these lesions (PMID:18061491)
• The relative protection against bone erosions in spondylarthritis cannot be explained by qualitative or quantitative differences in the synovial expression of RANKL, OPG, and RANK. (PMID:18311801)
• Data reveals for the first time that OPG/RANK/RANKL are expressed in the pathological thyroid gland by follicular cells, by malignant parafollicular cells as well as in metastatic lymph node microenvironment. (PMID:18367263)
• Osteoclast-poor osteopetrosis with agammaglobulinemia due to TNFRSF11A (RANK) mutation is reported. (PMID:18606301)
• ligation of RANK on DC cell surfaces is not only a survival stimulus, but also induces a partial and specific mature DC phenotype (PMID:18632421)
• Ineffective modulation of the OPG/RANK/RANKL system in active polyarticular juvenile idiopathic arthritis may account for bone damage in this disease. (PMID:18802807)
• might locally modulate [odontogenic] tumor-associated bone resorption (PMID:18928898)
• Based on their role in atherogenesis, this enhanced expression of RANKL and RANK could contribute to the increased risk of cardiovascular disease in hyperhomocystinemia (PMID:19008470)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdr	ENSDARG00000004392
danio_rerio	tnfrsfa	ENSDARG00000004451
danio_rerio	cd40	ENSDARG00000054968
danio_rerio	tnfrsf1b	ENSDARG00000070165
danio_rerio	tnfrsf11a	ENSDARG00000087804
mus_musculus	Tnfrsf11a	ENSMUSG00000026321
rattus_norvegicus	Tnfrsf11a	ENSRNOG00000015615

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), TNFRSF1A (ENSG00000067182), CD40 (ENSG00000101017), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF10B (ENSG00000120889), TNFRSF8 (ENSG00000120949), CD27 (ENSG00000139193), TNFRSF21 (ENSG00000146072), TNFRSF14 (ENSG00000157873), TNFRSF11B (ENSG00000164761), TNFRSF10D (ENSG00000173530), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 11A — Q9Y6Q6 (reviewed: Q9Y6Q6)

Alternative names: Osteoclast differentiation factor receptor, Receptor activator of NF-KB

All UniProt accessions (1): Q9Y6Q6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis. Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of NFATC1 and activation of PLCG2. Involved in the regulation of interactions between T-cells and dendritic cells.

Subunit / interactions. Binds to the clefts between the subunits of the TNFSF11 ligand trimer to form a heterohexamer. Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL. Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6. Interacts (via cytoplasmic domain) with GAB2. Interacts (via cytoplasmic domain); with EEIG1 (via N-terminus); when in the presence of TNFSF11/RANKL.

Subcellular location. Cell membrane. Membrane raft Cell membrane.

Tissue specificity. Ubiquitous expression with high levels in skeletal muscle, thymus, liver, colon, small intestine and adrenal gland.

Disease relevance. Familial expansile osteolysis (FEO) [MIM:174810] Rare autosomal dominant bone disorder characterized by focal areas of increased bone remodeling. The osteolytic lesions develop usually in the long bones during early adulthood. FEO is often associated with early-onset deafness and loss of dentition. The disease is caused by variants affecting the gene represented in this entry. Paget disease of bone 2, early-onset (PDB2) [MIM:602080] A form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. The disease is caused by variants affecting the gene represented in this entry. Osteopetrosis, autosomal recessive 7 (OPTB7) [MIM:612301] A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis 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. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB7 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development. OPTB7 is associated with hypogammaglobulinemia. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Reduced ability to bind RANKL and to activate NF-kappaB as compared to isoform 1.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9Y6Q6-1	1	yes
Q9Y6Q6-2	2, delta7,8,9
Q9Y6Q6-3	3, delta8,9
Q9Y6Q6-4	4, delta9
Q9Y6Q6-5	5, exon9a
Q9Y6Q6-6	RANK-e5a

RefSeq proteins (5): NP_001257878, NP_001257879, NP_001257880, NP_001265197, NP_003830* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR022323	TNFR_11	Family
IPR022361	TNFR_11A	Family
IPR034040	TNFRSF11A_N	Domain
IPR041648	RANK_CRD_2	Domain
IPR053075	TNFRSF11A	Family

Pfam: PF00020, PF18278

UniProt features (48 total): disulfide bond 10, sequence variant 9, splice variant 6, compositionally biased region 4, repeat 4, region of interest 3, binding site 3, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1LB5	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6Q6-F1	59.28	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 133; 134; 160

Post-translational modifications (1): 580

Disulfide bonds (10): 34–46, 47–60, 50–68, 71–86, 92–112, 114–127, 124–126, 133–151, 154–169, 175–194

Glycosylation sites (2): 105, 174

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-5676594	TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway

MSigDB gene sets: 485 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_REGULATION_OF_ICOSANOID_SECRETION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, LU_IL4_SIGNALING, GOBP_REGULATION_OF_PROSTAGLANDIN_SECRETION, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (27): ossification (GO:0001503), adaptive immune response (GO:0002250), monocyte chemotaxis (GO:0002548), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), response to mechanical stimulus (GO:0009612), osteoclast differentiation (GO:0030316), response to lipopolysaccharide (GO:0032496), response to insulin (GO:0032868), tumor necrosis factor-mediated signaling pathway (GO:0033209), cellular response to zinc ion starvation (GO:0034224), response to tumor necrosis factor (GO:0034612), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), response to ethanol (GO:0045471), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of bone resorption (GO:0045780), positive regulation of JNK cascade (GO:0046330), lymph node development (GO:0048535), circadian temperature homeostasis (GO:0060086), mammary gland alveolus development (GO:0060749), positive regulation of ERK1 and ERK2 cascade (GO:0070374), response to interleukin-1 (GO:0070555), positive regulation of fever generation by positive regulation of prostaglandin secretion (GO:0071812), multinuclear osteoclast differentiation (GO:0072674), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), immune system process (GO:0002376)

GO Molecular Function (6): transmembrane signaling receptor activity (GO:0004888), tumor necrosis factor receptor activity (GO:0005031), cytokine binding (GO:0019955), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane raft (GO:0045121), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytokine Signaling in Immune system	1
TNFR2 non-canonical NF-kB pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell communication	2
signaling	2
multicellular organismal process	1
immune response	1
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to external stimulus	1
response to abiotic stimulus	1
myeloid leukocyte differentiation	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
response to peptide hormone	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
cellular response to starvation	1
response to zinc ion starvation	1
response to cytokine	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
response to alcohol	1
positive regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
regulation of bone resorption	1
bone resorption	1
positive regulation of multicellular organismal process	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
hematopoietic or lymphoid organ development	1

Protein interactions and networks

STRING

1122 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF11A	TNFSF11	O14788	999
TNFRSF11A	NDUFAF3	Q9BU61	816
TNFRSF11A	OSTM1	Q86WC4	779
TNFRSF11A	CLCN7	P51798	772
TNFRSF11A	PSTPIP2	Q9H939	764
TNFRSF11A	PLEKHM1	Q9Y4G2	740
TNFRSF11A	TRAF6	Q9Y4K3	718
TNFRSF11A	TCIRG1	Q13488	714
TNFRSF11A	SQSTM1	Q13501	706
TNFRSF11A	CSF1	P09603	624
TNFRSF11A	ACP5	P13686	623
TNFRSF11A	TNF	P01375	612
TNFRSF11A	TNFRSF11B	O00300	610
TNFRSF11A	CD200R1	Q8TD46	602
TNFRSF11A	CTSK	P43235	588

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TNFSF11	TNFRSF11A	psi-mi:“MI:0407”(direct interaction)	0.620
TNFRSF11A	TNFSF11	psi-mi:“MI:0407”(direct interaction)	0.610
TRAF2	TNFRSF11A	psi-mi:“MI:0915”(physical association)	0.590
TNFRSF11A	TRAF2	psi-mi:“MI:0915”(physical association)	0.590
TNFRSF11A	TNFRSF11B	psi-mi:“MI:0915”(physical association)	0.540
TNFRSF11A	TNFRSF11B	psi-mi:“MI:0407”(direct interaction)	0.540
TMPRSS15	TNFRSF11A	psi-mi:“MI:0194”(cleavage reaction)	0.440
TNFRSF11A	TRAF5	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF11A	TRAF6	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (48): TNFRSF11A (Affinity Capture-RNA), TRAF6 (Affinity Capture-Western), GNB2L1 (Affinity Capture-Western), VAV3 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), TNFRSF11A (Affinity Capture-Western), TRAF2 (Affinity Capture-Western), TNFRSF11A (Co-localization), EGFR (Affinity Capture-Western), TNFRSF11A (Affinity Capture-Western), EGFR (Co-localization), TAB2 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), MAP3K7 (Affinity Capture-Western), TNFRSF11A (Proximity Label-MS)

ESM2 similar proteins: D3ZF92, D5K8A9, O00220, O14763, O15553, O35305, O35714, O75509, P12342, P20333, P22934, P25118, P25119, P26898, P27987, P28908, P50284, P97525, Q2YDG7, Q3U4N7, Q5HZW5, Q5ND28, Q5PQX1, Q60846, Q80WY6, Q86T13, Q86VZ4, Q8BX35, Q8BZW2, Q8CB67, Q8IY92, Q8NC42, Q8TBE3, Q8VCP9, Q8WWF5, Q90VY2, Q921T2, Q96L08, Q9DA48, Q9EPU5

Diamond homologs: A5D7R1, D3ZF92, O00300, O08712, O08727, O35305, O75509, O95407, P0DTN0, P20333, P25119, P25942, P25943, P27512, P29825, P36941, P43489, P83626, Q28203, Q3LRP1, Q3ZTK5, Q63199, Q7YRL5, Q8SQ34, Q9EPU5, Q9Y6Q6, O73559, P0DSV7, P0DSV8, P68636, P68637, P28908, P07174, P08138, P15725, P20334, P47741, P50284, Q07011, Q9Z0W1

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TNFSF11	“up-regulates activity”	TNFRSF11A	binding
TNFRSF11A	up-regulates	Osteoclast_differentiation
TRAF6	“up-regulates activity”	TNFRSF11A	binding
TNFRSF11A	“up-regulates activity”	NfKb-p65/p50
CNOT3	“down-regulates quantity by repression”	TNFRSF11A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

759 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	10
Uncertain significance	436
Likely benign	203
Benign	41

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1368167	NM_003839.4(TNFRSF11A):c.1079T>A (p.Leu360Ter)	Pathogenic
1404925	NM_003839.4(TNFRSF11A):c.396del (p.Glu132fs)	Pathogenic
1684671	NM_003839.4(TNFRSF11A):c.1530dup (p.Ser511fs)	Pathogenic
2009862	NM_003839.4(TNFRSF11A):c.1267C>T (p.Gln423Ter)	Pathogenic
2097157	NM_003839.4(TNFRSF11A):c.720del (p.Ala241fs)	Pathogenic
2424776	NC_000018.9:g.(?60015381)(60017190_?)del	Pathogenic
2444185	NM_003839.4(TNFRSF11A):c.54C>A (p.Cys18Ter)	Pathogenic
2574148	NM_003839.4(TNFRSF11A):c.239G>A (p.Trp80Ter)	Pathogenic
2700222	NM_003839.4(TNFRSF11A):c.360G>A (p.Trp120Ter)	Pathogenic
2707448	NM_003839.4(TNFRSF11A):c.1005del (p.Ile335fs)	Pathogenic
2866721	NM_003839.4(TNFRSF11A):c.975del (p.Met326fs)	Pathogenic
2991161	NM_003839.4(TNFRSF11A):c.447_448del (p.Cys151fs)	Pathogenic
3722218	NM_003839.4(TNFRSF11A):c.364C>T (p.Gln122Ter)	Pathogenic
6301	NM_003839.4(TNFRSF11A):c.508A>G (p.Arg170Gly)	Pathogenic
6302	NM_003839.4(TNFRSF11A):c.523T>C (p.Cys175Arg)	Pathogenic
6304	NM_003839.4(TNFRSF11A):c.730G>T (p.Ala244Ser)	Pathogenic
6305	NM_003839.4(TNFRSF11A):c.157G>C (p.Gly53Arg)	Pathogenic
1518315	NM_003839.4(TNFRSF11A):c.427+1G>A	Likely pathogenic
1684669	NM_003839.4(TNFRSF11A):c.147A>C (p.Lys49Asn)	Likely pathogenic
1684670	NM_003839.4(TNFRSF11A):c.380G>A (p.Cys127Tyr)	Likely pathogenic
2003588	NM_003839.4(TNFRSF11A):c.427+2T>G	Likely pathogenic
2500800	NM_003839.4(TNFRSF11A):c.328dup (p.Arg110fs)	Likely pathogenic
2572028	NM_003839.4(TNFRSF11A):c.443A>T (p.Asp148Val)	Likely pathogenic
3640205	NM_003839.4(TNFRSF11A):c.521+1G>C	Likely pathogenic
3664269	NM_003839.4(TNFRSF11A):c.784-1G>A	Likely pathogenic
4812937	NM_003839.4(TNFRSF11A):c.1075C>T (p.Gln359Ter)	Likely pathogenic
817702	NM_003839.4(TNFRSF11A):c.1266_1268delinsCC (p.Leu422fs)	Likely pathogenic

SpliceAI

2292 predictions. Top by Δscore:

Variant	Effect	Δscore
18:62325426:AGGTA:A	donor_loss	1.0000
18:62325428:GTA:G	donor_loss	1.0000
18:62325429:T:G	donor_loss	1.0000
18:62343358:A:T	donor_gain	1.0000
18:62348290:GTGG:G	donor_gain	1.0000
18:62354503:G:GG	donor_gain	1.0000
18:62354533:GT:G	donor_gain	1.0000
18:62358246:A:AG	acceptor_gain	1.0000
18:62358247:G:GA	acceptor_gain	1.0000
18:62358247:GTGCA:G	acceptor_gain	1.0000
18:62358342:G:GG	donor_gain	1.0000
18:62359953:A:AG	acceptor_gain	1.0000
18:62359954:G:GG	acceptor_gain	1.0000
18:62359954:GCT:G	acceptor_gain	1.0000
18:62361673:A:AG	acceptor_gain	1.0000
18:62325424:GCAG:G	donor_gain	0.9900
18:62325428:G:GG	donor_gain	0.9900
18:62343361:G:GG	donor_gain	0.9900
18:62348690:T:G	acceptor_gain	0.9900
18:62349802:T:G	acceptor_gain	0.9900
18:62349809:AAG:A	acceptor_gain	0.9900
18:62349810:A:G	acceptor_gain	0.9900
18:62349811:GGAAA:G	acceptor_gain	0.9900
18:62349850:A:AG	acceptor_gain	0.9900
18:62349851:G:GG	acceptor_gain	0.9900
18:62349933:TACAG:T	donor_loss	0.9900
18:62349934:ACAG:A	donor_loss	0.9900
18:62349935:CAG:C	donor_loss	0.9900
18:62349936:AGGT:A	donor_loss	0.9900
18:62349937:GGT:G	donor_loss	0.9900

AlphaMissense

4026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:62349910:T:A	C86S	0.999
18:62349911:G:C	C86S	0.999
18:62384780:T:C	F533L	0.999
18:62384782:C:A	F533L	0.999
18:62384782:C:G	F533L	0.999
18:62349910:T:C	C86R	0.998
18:62349928:T:A	C92S	0.998
18:62349929:G:C	C92S	0.998
18:62384781:T:C	F533S	0.998
18:62384781:T:G	F533C	0.998
18:62384806:C:A	N541K	0.998
18:62384806:C:G	N541K	0.998
18:62349912:C:G	C86W	0.997
18:62349928:T:C	C92R	0.997
18:62349929:G:A	C92Y	0.997
18:62354449:C:G	C114W	0.997
18:62384784:T:A	I534N	0.997
18:62384784:T:C	I534T	0.997
18:62384807:T:C	F542L	0.997
18:62384808:T:C	F542S	0.997
18:62384809:C:A	F542L	0.997
18:62384809:C:G	F542L	0.997
18:62384823:T:A	I547N	0.997
18:62384829:T:A	V549D	0.997
18:62348240:T:A	C50S	0.996
18:62348241:G:C	C50S	0.996
18:62349865:T:A	C71S	0.996
18:62349866:G:C	C71S	0.996
18:62354447:T:A	C114S	0.996
18:62354448:G:A	C114Y	0.996

dbSNP variants (sampled 300 via entrez): RS1000063717 (18:62387711 A>G), RS1000071065 (18:62343655 A>G), RS1000138400 (18:62340274 A>G), RS1000162948 (18:62349664 A>C,T), RS1000175246 (18:62378726 G>C,T), RS1000176190 (18:62334430 C>G), RS1000202392 (18:62383139 T>A,C), RS1000208605 (18:62328065 T>C), RS1000289830 (18:62378450 T>G), RS1000336428 (18:62371716 A>G), RS1000337265 (18:62364630 C>G), RS1000371162 (18:62336972 G>A), RS1000418466 (18:62384953 C>T), RS1000429089 (18:62356453 T>G), RS1000456275 (18:62390900 G>A)

Disease associations

OMIM: gene MIM:603499 | disease phenotypes: MIM:174810, MIM:612301, MIM:602080

GenCC curated gene-disease

Disease	Classification	Inheritance
Paget disease of bone 2, early-onset	Strong	Autosomal dominant
autosomal recessive osteopetrosis 7	Strong	Autosomal recessive
familial expansile osteolysis	Moderate	Autosomal dominant
dysosteosclerosis	Supportive	Autosomal recessive
osteosarcoma	Limited	Autosomal dominant

Mondo (7): familial expansile osteolysis (MONDO:0008275), autosomal recessive osteopetrosis 7 (MONDO:0012859), Paget disease of bone 2, early-onset (MONDO:0011183), bone disorder (MONDO:0005381), intellectual disability (MONDO:0001071), dysosteosclerosis (MONDO:0009138), osteosarcoma (MONDO:0009807)

Orphanet (4): Familial expansile osteolysis (Orphanet:85195), Osteopetrosis-hypogammaglobulinemia syndrome (Orphanet:178389), Rare bone disease related to a common gene or pathway defect (Orphanet:364803), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

88 total (30 of 88 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000520	Proptosis
HP:0000529	Progressive visual loss
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000889	Abnormal clavicle morphology
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0000944	Abnormal metaphysis morphology
HP:0000995	Melanocytic nevus
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001291	Abnormal cranial nerve morphology
HP:0001482	Subcutaneous nodule
HP:0001510	Growth delay
HP:0001522	Death in infancy
HP:0001629	Ventricular septal defect

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST000181_2	Bone mineral density (hip)	1.000000e-06
GCST000494_11	Bone mineral density (spine)	9.000000e-09
GCST000672_1	Paget’s disease	5.000000e-13
GCST000672_3	Paget’s disease	2.000000e-11
GCST001086_3	Paget’s disease	8.000000e-21
GCST001482_16	Lumbar spine bone mineral density	2.000000e-17
GCST001699_10	Serum albumin levels	4.000000e-09
GCST001699_16	Serum albumin levels	1.000000e-08
GCST001773_3	Response to antipsychotic treatment	3.000000e-07
GCST002493_11	Bone mineral density (paediatric, skull)	2.000000e-08
GCST002493_12	Bone mineral density (paediatric, skull)	2.000000e-07
GCST002838_3	Myasthenia gravis	1.000000e-08
GCST004785_45	Vitiligo	3.000000e-10
GCST005038_52	Allergic disease (asthma, hay fever or eczema)	7.000000e-09
GCST005795_8	Femoral neck bone mineral density	6.000000e-10
GCST005796_31	Lumbar spine bone mineral density	2.000000e-12
GCST006016_29	Serum alkaline phosphatase levels	5.000000e-11
GCST006288_367	Heel bone mineral density	1.000000e-10
GCST006288_667	Heel bone mineral density	1.000000e-18
GCST006288_68	Heel bone mineral density	3.000000e-09
GCST006585_1858	Blood protein levels	4.000000e-11
GCST006979_729	Heel bone mineral density	6.000000e-10
GCST006979_730	Heel bone mineral density	6.000000e-38
GCST007797_23	Asthma onset (childhood vs adult)	4.000000e-09
GCST007800_105	Asthma (childhood onset)	8.000000e-14
GCST007994_22	Asthma (age of onset)	2.000000e-10
GCST007995_6	Asthma (childhood onset)	9.000000e-09
GCST010042_33	Asthma	1.000000e-09
GCST010043_41	Asthma	1.000000e-09
GCST010984_43	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	2.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007785	femoral neck bone mineral density
EFO:0007701	spine bone mineral density
EFO:0004533	alkaline phosphatase measurement
EFO:0009270	heel bone mineral density
EFO:0004847	age at onset

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D001847	Bone Diseases	C05.116
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D012516	Osteosarcoma	C04.557.450.565.575.650; C04.557.450.795.620
C562973	Dysosteosclerosis (supp.)
C567354	Osteopetrosis, Autosomal Recessive 7 (supp.)
C536335	Polyostotic osteolytic dysplasia, hereditary expansile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1805034	Toxicity	3	acetaminophen;aspirin;diclofenac;propionic acid derivatives;Pyrazolones
rs2980976	Efficacy	3	risperidone	Schizophrenia

PharmGKB variants

21 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1805034	TNFRSF11A	3	2.50	1	acetaminophen;aspirin;diclofenac;propionic acid derivatives;Pyrazolones
rs3826619	TNFRSF11A		0.00	0
rs4369774	TNFRSF11A		0.00	0
rs4941129	TNFRSF11A		0.00	0
rs4941131	TNFRSF11A		0.00	0
rs6567270	TNFRSF11A		0.00	0
rs6567276	TNFRSF11A		0.00	0
rs7231887	TNFRSF11A		0.00	0
rs7237982	TNFRSF11A		0.00	0
rs7239261	TNFRSF11A		0.00	0
rs7239667	TNFRSF11A		0.00	0
rs8083511	TNFRSF11A		0.00	0
rs9646629	TNFRSF11A		0.00	0
rs11664594	TNFRSF11A		0.00	0
rs11877530	TNFRSF11A		0.00	0
rs12455775	TNFRSF11A		0.00	0
rs12457042	TNFRSF11A		0.00	0
rs12458117	TNFRSF11A		0.00	0
rs12956925	TNFRSF11A		0.00	0
rs12969154	TNFRSF11A		0.00	0
rs17069895	TNFRSF11A		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Tumour necrosis factor (TNF) receptor family

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, increases mutagenesis	7
Valproic Acid	increases expression, affects cotreatment	6
Arsenic Trioxide	decreases expression, increases expression	3
trichostatin A	affects expression, decreases expression	2
Acetaminophen	increases expression	2
Cisplatin	decreases expression, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
2-anisidine	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
glycidamide	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases reaction, increases expression	1
Allergens	increases expression	1
Arsenic	affects expression	1
Biological Factors	decreases expression	1
Cadmium	increases abundance, decreases expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Drugs, Chinese Herbal	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8CJ	HEK-Blue RANKL	Transformed cell line	Female
CVCL_E6V5	Genomeditech HEK-293 H_TNFRSF11A(RANK) Reporter	Transformed cell line	Female
CVCL_LB26	PathHunter U2OS RANK-IkappaB Functional Assay	Cancer cell line	Female

Clinical trials (associated diseases)

500 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01669369	PHASE4	UNKNOWN	Clinical Trial of Lithium Carbonate Combined With Neo-adjuvant Chemotherapy to Treat Osteosarcoma
NCT04854018	PHASE4	COMPLETED	Indo-cyanine Green (ICG) in Paediatric Oncology MIS
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00001217	PHASE3	COMPLETED	Osteosarcoma Study #2: A Randomized Trial of Pre-Surgical Chemotherapy vs. Immediate Surgery and Adjuvant Chemotherapy in the Treatment of Non-Metastatic Osteosarcoma. A Pediatric Oncology Group Phase III Study
NCT00134030	PHASE3	COMPLETED	Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma
NCT00180908	PHASE3	COMPLETED	Comparison of High-Dose Methotrexate (HDM) Plus Doxorubicin to HDM Plus Etoposide-Ifosfamide in Osteosarcoma Children
NCT01176981	PHASE3	COMPLETED	Outpatient Administration of High Dose Methotrexate (HD MTX) in Patients With Osteosarcoma
NCT01987596	PHASE3	TERMINATED	Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer
NCT05024253	PHASE3	COMPLETED	Perioperative Use of Tranexamic (TXA) in Bone Tumor Surgery Will Change in Blood Loss and Transfusion Requirements.
NCT05235165	PHASE3	RECRUITING	Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
NCT05328258	PHASE3	RECRUITING	Use of GnRHa During Chemotherapy for Fertility Protection
NCT06935409	PHASE3	ACTIVE_NOT_RECRUITING	Study of HS-20093 Versus Gemcitabine in Combination With Docetaxel in Treatment of Osteosarcoma After Previous Second-line Treatment Failure
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00004078	PHASE2	COMPLETED	Irinotecan in Treating Children With Refractory Solid Tumors
NCT00023998	PHASE2	COMPLETED	Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma
NCT00030667	PHASE2	COMPLETED	Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood
NCT00038207	PHASE2	COMPLETED	Liposomal Vincristine for Pediatric and Adolescent Patients With Relapsed Malignancies
NCT00091182	PHASE2	COMPLETED	Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment
NCT00093080	PHASE2	COMPLETED	Study of AP23573/MK-8669 (Ridaforolimus), A Mammalian Target of Rapamycin (mTOR) Inhibitor, in Participants With Advanced Sarcoma (MK-8669-018 AM1)(COMPLETED)
NCT00145639	PHASE2	COMPLETED	Osteosarcoma1999-A Study Of Intensive Chemotherapy for Osteosarcoma
NCT00180947	PHASE2	UNKNOWN	Study of Vinorelbine and Cyclofosfamide Among Patients With Refractory Tumours or in Relapse
NCT00330421	PHASE2	COMPLETED	Sorafenib in Treating Patients With Soft Tissue Sarcomas (Extremity Sarcoma Closed to Entry as of 5/30/07)
NCT00331643	PHASE2	COMPLETED	Ixabepilone in Treating Young Patients With Refractory Solid Tumors
NCT00407433	PHASE2	COMPLETED	Clinical Studies of Gemcitabine-Oxaliplatin
NCT00503295	PHASE2	COMPLETED	Safety and Efficacy Study of REOLYSIN® in the Treatment of Bone and Soft Tissue Sarcomas Metastatic to the Lung
NCT00504140	PHASE2	COMPLETED	Recombinant Interferon Alpha and Etoposide in Relapsed Osteosarcoma
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00523419	PHASE2	COMPLETED	Chemotherapy for Patients With Osteosarcoma
NCT00572130	PHASE2	COMPLETED	Phase II Study of Intravenous Rexin-G in Osteosarcoma
NCT00586846	PHASE2	COMPLETED	Phase II Study of Chemotherapy and Pamidronate for the Treatment of Newly Diagnosed Osteosarcoma
NCT00617890	PHASE2	TERMINATED	A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing’s Sarcoma (MK-7454-002/P04720)
NCT00634322	PHASE2	TERMINATED	High Dose Methotrexate With Leucovorin Rescue With or Without Glucarpidase in Osteosarcoma
NCT00667342	PHASE2	COMPLETED	A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma
NCT00743509	PHASE2	COMPLETED	A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma
NCT00752206	PHASE2	TERMINATED	A Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung
NCT00831844	PHASE2	COMPLETED	Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer