TNFRSF10B

Summary

TNFRSF10B (TNF receptor superfamily member 10b, HGNC:11905) is a protein-coding gene on chromosome 8p21.3, encoding Tumor necrosis factor receptor superfamily member 10B (O14763). Receptor for the cytotoxic ligand TNFSF10/TRAIL.

The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces an apoptosis signal. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for this gene.

Source: NCBI Gene 8795 — RefSeq curated summary.

At a glance

• Gene–disease (curated): head and neck squamous cell carcinoma (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 90 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_003842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11905
Approved symbol	TNFRSF10B
Name	TNF receptor superfamily member 10b
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, CD262, TRAILR2
Ensembl gene	ENSG00000120889
Ensembl biotype	protein_coding
OMIM	603612
Entrez	8795

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000276431, ENST00000347739, ENST00000518531, ENST00000519028, ENST00000519910, ENST00000520109, ENST00000523504, ENST00000523752, ENST00000867256, ENST00000867257, ENST00000867258, ENST00000931215, ENST00000931216, ENST00000945966

RefSeq mRNA: 2 — MANE Select: NM_003842 NM_003842, NM_147187

CCDS: CCDS6035, CCDS6036

Canonical transcript exons

ENST00000276431 — 9 exons

Exon	Start	End
ENSE00001203553	23028331	23028602
ENSE00003479207	23068751	23069031
ENSE00003560985	23043138	23043243
ENSE00003566418	23030759	23030872
ENSE00003582358	23027722	23027753
ENSE00003622134	23020133	23022984
ENSE00003643584	23027133	23027288
ENSE00003649269	23024188	23024260
ENSE00003688925	23029610	23029721

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.5017 / max 413.8529, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92279	37.1663	1802
92278	11.5227	1619
92280	2.0019	1225
92281	0.4099	160
92275	0.4008	209

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	98.05	gold quality
mucosa of urinary bladder	UBERON:0001259	96.89	gold quality
blood	UBERON:0000178	96.55	gold quality
vena cava	UBERON:0004087	96.50	gold quality
cervix squamous epithelium	UBERON:0006922	96.10	gold quality
stromal cell of endometrium	CL:0002255	95.97	gold quality
gall bladder	UBERON:0002110	95.68	gold quality
germinal epithelium of ovary	UBERON:0001304	95.62	gold quality
pericardium	UBERON:0002407	95.47	gold quality
visceral pleura	UBERON:0002401	95.36	gold quality
tibia	UBERON:0000979	95.29	gold quality
monocyte	CL:0000576	94.92	gold quality
pancreatic ductal cell	CL:0002079	94.80	gold quality
mononuclear cell	CL:0000842	94.75	gold quality
leukocyte	CL:0000738	94.68	gold quality
pleura	UBERON:0000977	94.64	gold quality
parietal pleura	UBERON:0002400	94.62	gold quality
choroid plexus epithelium	UBERON:0003911	94.58	gold quality
granulocyte	CL:0000094	94.53	gold quality
epithelium of nasopharynx	UBERON:0001951	94.42	gold quality
nasopharynx	UBERON:0001728	94.40	gold quality
palpebral conjunctiva	UBERON:0001812	94.37	gold quality
right lobe of liver	UBERON:0001114	93.85	gold quality
right adrenal gland cortex	UBERON:0035827	93.85	gold quality
epithelial cell of pancreas	CL:0000083	93.70	gold quality
body of pancreas	UBERON:0001150	93.69	gold quality
gingival epithelium	UBERON:0001949	93.63	gold quality
liver	UBERON:0002107	93.56	gold quality
adrenal cortex	UBERON:0001235	93.21	gold quality
upper lobe of left lung	UBERON:0008952	93.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.69
E-GEOD-93593	yes	7.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARID1B, ATF3, ATF4, ATM, DDIT3, DNMT1, DNMT3B, EHF, ELK1, ETS1, GATA1, GLI1, GLI2, GSN, HDAC9, JUN, MYB, MYC, NFKB1, NFKB, RELA, SIRT1, SP1, SPI1, STAT1, STAT3, TP53, YY1

miRNA regulators (miRDB)

78 targeting TNFRSF10B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4437	99.52	65.29	1266

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure at 2.2 A resolution of a complex between TRAIL and the extracellular region of DR5 (PMID:10542098)
• TNF-related apoptosis-inducing ligand (TRAIL) is not constitutively expressed in the human brain, whereas both apoptosis-mediating and apoptosis-blocking TRAIL receptors are found on neurons, astrocytes, and oligodendrocytes (PMID:11844843)
• highly expressed in metastatic gastric carcinoma and tumor-infiltrating lymphocytes (PMID:11862476)
• examined whether TRAIL receptors use different intermediates to convey the apoptotic signal to mitochondria (PMID:12196516)
• cholestasis increased both liver TRAIL-R2/DR5 mRNA and protein expression (>10-fold) (PMID:12388624)
• Tyrosine-based sorting signal in adenovirus RID plays a role in RID’s ability to down-regulate TRAIL receptor 2 and inhibit TRAIL induced apoptosis (PMID:12388693)
• Decreased expression of DR5 may contribute to prolonged survival of eosinophils in the airways of allergic asthmatics following segmental antigen challenge. (PMID:12421985)
• Cytotoxicity and apoptosis induced by TRAIL to beta-cell lines CM were inhibited competitively by soluble TRAIL receptors, R1, R2, R3 or R4. (PMID:12488957)
• role of upregulation in interferon-alpha sensitized hepatoma cells to TRAIL-induced apoptosis (PMID:12642868)
• likely to be involved in chronic pancreatitis; pancreatic stellate cells may directly contribute to acinar regression by inducing apoptosis of parenchymal cells in a TRAIL-dependent manner (PMID:12808117)
• Like malignantly transformed cells, synovial cells from rheumatoid arthritis patients express high levels of DR5 and are highly susceptible to DR5-mediated apoptosis. (PMID:12847280)
• Respiratory syncytial virus infection strongly up-regulated the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its functional receptors death receptor 4 (DR4) and DR5. (PMID:12915532)
• results show that protein kinase C activation specifically inhibits the recruitment of TRAIL receptors 1 and 2 complexes, thereby modulating tumor necrosis-related apoptosis-inducing ligand(TRAIL)-induced apoptosis (PMID:12920112)
• Infection of primary cells with adenoviruses carrying the relevant point mutations confirmed the crucial role of putative YXX Phi and dileucine (LL) transport motifs within Ad2 10.4-14.5 for down-regulation of Fas, TRAIL-R1, TRAIL-R2, and EGFR. (PMID:14506242)
• Fas, DR4, and DR5 are activated in drug-sensitive cells in response to anticancer drugs depending on the cytotoxic effect of each drug (PMID:14534720)
• Sp1 is a bile acid-responsive transcription factor that mediates DR5/TRAIL-R2 gene expression downstream of JNK. (PMID:14561739)
• All of mAbs to TRAIL-R1 and TRAIL-R2 induced cell death in several cancer cell lines susceptible to TRAIL but not in human umbilical vein endothelial cells in vitro (PMID:14576771)
• TRAIL-R2 expression is post-transcriptionally regulated by cytosolic proteins induced by TRAIL that bind to the 3’-UTR region of TRAIL-R2 mRNA (PMID:14688276)
• MG132 upregulates death receptor 5 and cooperates with APO2L to induce apoptosis in Bax-proficient and -deficient cells. (PMID:14691451)
• binding of Fas-associated death domain (FADD) to the tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 is regulated by the death effector domain of FADD (PMID:15173180)
• Malignant mesothelioma cells develop anintrinsic resistance to apoptosis induced by death receptor-4 upregulating the expression of the antiapoptotic protein c-FLIP. (PMID:15334061)
• DR4 and DR5 are differentially regulated by the signal recognition particle (PMID:15356269)
• in addition to the death domain, the C-terminal tails of DR4 and DR5 positively regulate FADD binding, caspase activation and apoptosis (PMID:15452120)
• CD95, DR4 and DR5 localization in rafts have roles in the toxicity of resveratrol and death receptor ligands in colon carcinoma cells (PMID:15480430)
• c-FLIPL is recruited to death receptor 5 independent of Fas-associated protein with death domain (FADD) (PMID:15485835)
• Although ischemic liver injury was not serious, due to the short ischemia time, TNFR1 and TRAIL are associated with liver ischemic injury in live-donor liver transplantation but Fas is not. (PMID:15502938)
• Adenovirus E3-6.7K protein is required in conjunction with the E3-RID protein complex for the internalization and degradation of TRAIL receptor 2. (PMID:15507617)
• DR5 may contribute more than DR4 to Apo2L/TRAIL-induced apoptosis in cancer cells that express both death receptors (PMID:15520016)
• The death receptor 5 was widely expressed on both normal and maliganat cells (PMID:15538968)
• The TRAILR2 is expressed by humans thymocytes, which appear to be functional since considerable cell death was observed upon receptor ligation. (PMID:15608691)
• in patients infected with cagA+/vacAs1+ H. pylori strains, expression of TRAIL and TRAIL-R1 and -R2 was down-regulated; down-regulation may limit apoptosis of gastric epithelial cells & destruction of tissue and may enable H. pylori to maintain its niche (PMID:15655781)
• In colorectal carcinogenesis, there is a marked increase in sensitivity to TRAIL-induced apoptosis with progression from benign to malignant tumor, but alterations in cell surface TRAIL receptor expression may not be the primary reason for this change. (PMID:15685228)
• RAS-MEK-ERK1/2 signaling pathway can sensitize cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5 (PMID:15757891)
• addition in culture of TRAIL-R2-Fc chimera, which blocked the interaction between endogenous TRAIL and TRAIL-R2 on the surface of cultured megakaryocytic cells, increased the total megakaryocytic cell count (PMID:15828026)
• TRAIL-R2 downmodulation results in resistance to TRAIL-mediated apoptosis in acute myeloid leukemia. (PMID:15921376)
• Extensive regions of the FADD death domain are required for binding to the TRAIL receptor DR5. (PMID:16003390)
• Luteolin induces apoptosis via DR5 up-regulation in malignant tumor cells. (PMID:16007131)
• TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma (PMID:16051735)
• TRAIL-R2 apoptotic pathway plays an important role in hepatic cell death during viral infection. (PMID:16226105)
• The expression level of TRAIL receptor DR5 in the fibroblasts of hypertrophic burn scar is much lower than the control. (PMID:16463784)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdr	ENSDARG00000004392
danio_rerio	tnfrsfa	ENSDARG00000004451
danio_rerio	cd40	ENSDARG00000054968
danio_rerio	nradd	ENSDARG00000057143
danio_rerio	tnfrsf1b	ENSDARG00000070165
danio_rerio	tnfrsf11a	ENSDARG00000087804
mus_musculus	Tnfrsf22	ENSMUSG00000010751
mus_musculus	Tnfrsf23	ENSMUSG00000037613
mus_musculus	Tnfrsf26	ENSMUSG00000045362
rattus_norvegicus	Tnfrsf26	ENSRNOG00000043486
rattus_norvegicus	Tnfrsf22	ENSRNOG00000070689

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), TNFRSF1A (ENSG00000067182), CD40 (ENSG00000101017), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF8 (ENSG00000120949), CD27 (ENSG00000139193), TNFRSF11A (ENSG00000141655), 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 10B — O14763 (reviewed: O14763)

Alternative names: Death receptor 5, TNF-related apoptosis-inducing ligand receptor 2

All UniProt accessions (2): E9PBT3, O14763

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.

Subunit / interactions. Monomer. Can interact with TRADD and RIPK1. Interacts with HCMV protein UL141; this interaction prevents TNFRSF10B cell surface expression. Two TNFRSF10B monomers interact with a UL141 homodimer. Three TNFRSF10B molecules interact with TNFSF10 homotrimer. In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2 cleavage.

Subcellular location. Membrane.

Tissue specificity. Widely expressed in adult and fetal tissues; very highly expressed in tumor cell lines such as HeLaS3, K-562, HL-60, SW480, A-549 and G-361; highly expressed in heart, peripheral blood lymphocytes, liver, pancreas, spleen, thymus, prostate, ovary, uterus, placenta, testis, esophagus, stomach and throughout the intestinal tract; not detectable in brain.

Post-translational modifications. (Microbial infection) Glycosylated on Arg residue by S.typhimurium protein Ssek3.

Disease relevance. Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355] A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. The disease may be caused by variants affecting the gene represented in this entry.

Induction. By ER stress. Regulated by p53/TP53.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
O14763-1	Long, TRICK2B	yes
O14763-3	3
O14763-2	Short, TRICK2A

RefSeq proteins (2): NP_003833, NP_671716 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR020465	TNFR_10	Family
IPR034024	TNFRSF10_N	Domain
IPR034029	TNFRSF10A/B_death	Domain
IPR052491	TNFRSF10	Family

Pfam: PF00020, PF00531

UniProt features (45 total): strand 16, disulfide bond 7, repeat 4, sequence variant 3, region of interest 2, topological domain 2, splice variant 2, helix 2, signal peptide 1, chain 1, compositionally biased region 1, sequence conflict 1, transmembrane region 1, turn 1, domain 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3X3F	X-RAY DIFFRACTION	2.1
4I9X	X-RAY DIFFRACTION	2.1
1D4V	X-RAY DIFFRACTION	2.2
1DU3	X-RAY DIFFRACTION	2.2
2H9G	X-RAY DIFFRACTION	2.32
1D0G	X-RAY DIFFRACTION	2.4
6T3J	X-RAY DIFFRACTION	3.05
4OD2	X-RAY DIFFRACTION	3.2
4N90	X-RAY DIFFRACTION	3.3
1ZA3	X-RAY DIFFRACTION	3.35
6NHW	SOLUTION NMR
6NHY	SOLUTION NMR
8DPX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14763-F1	71.76	0.41

Antibody-complex structures (SAbDab): 6 — 1ZA3, 2H9G, 3X3F, 4N90, 4OD2, 6T3J

Functional residue map

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

Disulfide bonds (7): 81–94, 97–113, 116–129, 119–137, 139–153, 156–170, 160–178

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-140534	Caspase activation via Death Receptors in the presence of ligand
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-3371378	Regulation by c-FLIP
R-HSA-5213460	RIPK1-mediated regulated necrosis
R-HSA-5218900	CASP8 activity is inhibited
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-69416	Dimerization of procaspase-8
R-HSA-75158	TRAIL signaling

MSigDB gene sets: 300 (showing top): MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, LEE_NEURAL_CREST_STEM_CELL_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, MODULE_45, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_ACTIVATION_OF_NF_KAPPAB_INDUCING_KINASE_ACTIVITY, GOCC_CELL_SURFACE, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, KYNG_DNA_DAMAGE_DN, MODULE_16

GO Biological Process (13): defense response to tumor cell (GO:0002357), apoptotic process (GO:0006915), cell surface receptor signaling pathway (GO:0007166), activation of NF-kappaB-inducing kinase activity (GO:0007250), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), response to endoplasmic reticulum stress (GO:0034976), TRAIL-activated apoptotic signaling pathway (GO:0036462), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), cellular response to mechanical stimulus (GO:0071260), signal transduction (GO:0007165)

GO Molecular Function (5): TRAIL receptor activity (GO:0036463), signaling receptor activity (GO:0038023), TRAIL binding (GO:0045569), death receptor activity (GO:0005035), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Caspase activation via Death Receptors in the presence of ligand	2
Caspase activation via extrinsic apoptotic signalling pathway	1
Hemostasis	1
Regulated Necrosis	1
Regulation of necroptotic cell death	1
TP53 Regulates Transcription of Cell Death Genes	1
Death Receptor Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	2
apoptotic process	2
cellular anatomical structure	2
response to tumor cell	1
defense response	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
signal transduction	1
activation of protein kinase activity	1
non-canonical NF-kappaB signal transduction	1
extrinsic apoptotic signaling pathway	1
cellular response to stress	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of programmed cell death	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
response to endoplasmic reticulum stress	1
intrinsic apoptotic signaling pathway	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
death receptor activity	1
TRAIL-activated apoptotic signaling pathway	1
TRAIL binding	1
molecular transducer activity	1
protein binding	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2176 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF10B	TNFSF10	P50591	999
TNFRSF10B	FADD	Q13158	998
TNFRSF10B	TNF	P01375	997
TNFRSF10B	FASLG	P48023	997
TNFRSF10B	CASP8	Q14790	991
TNFRSF10B	CFLAR	O15519	922
TNFRSF10B	TNFRSF10A	O00220	919
TNFRSF10B	FAS	P25445	917
TNFRSF10B	TNFSF12	O43508	890
TNFRSF10B	TNFRSF21	O75509	889
TNFRSF10B	TRADD	Q15628	878
TNFRSF10B	RIPK1	Q13546	874
TNFRSF10B	TNFRSF10C	O14798	858
TNFRSF10B	TP53	P04637	822
TNFRSF10B	PIDD1	Q9HB75	818

IntAct

165 interactions, top by confidence:

A	B	Type	Score
TNFRSF10B	TNFSF10	psi-mi:“MI:0407”(direct interaction)	0.950
TNFSF10	TNFRSF10B	psi-mi:“MI:0914”(association)	0.950
TNFSF10	TNFRSF10B	psi-mi:“MI:0407”(direct interaction)	0.950
CASP8	TNFRSF10A	psi-mi:“MI:0914”(association)	0.820
TNFSF10	TNFRSF10A	psi-mi:“MI:0914”(association)	0.800
CASP8	TNFRSF10B	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
TNFRSF10B	ASPH	psi-mi:“MI:0915”(physical association)	0.560
	TNFRSF10B	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10B	ZDHHC15	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10B	MUC1	psi-mi:“MI:0915”(physical association)	0.560
FYN	SDCBP	psi-mi:“MI:0914”(association)	0.550

BioGRID (289): TNFRSF10B (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), LSR (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), SLC15A4 (Affinity Capture-MS), PTRH2 (Affinity Capture-MS), SCAMP1 (Affinity Capture-MS), REEP5 (Affinity Capture-MS)

ESM2 similar proteins: A5D7R1, D3ZF92, F1LW30, O00300, O08712, O08727, O14763, O62802, O70458, O70535, O75509, O77736, O95256, P01590, P20334, P20352, P22934, P25118, P25445, P25446, P26897, P30836, P41690, P42703, P51867, P83626, Q07011, Q13478, Q5M9I1, Q61098, Q63199, Q65Z14, Q6UXZ4, Q6X782, Q6X784, Q6X786, Q764M8, Q8K1S2, Q8K5B1, Q90VY2

Diamond homologs: O00220, O14763, O14798, P15725, P47741, P83626, Q9QZM4, Q9UBN6, O19131, P19438, P50555, Q80WM9, O00300, O77736, O73559, P0DSV7, P0DSV8, P0DTN0, P22934, P25118, P25943, P68636, P68637, Q80WY6, Q92956, Q9ER62, Q9ER63, O35305, P43489, P50284, Q9Y6Q6, P29825, P36941, Q76ZJ3, O35714, P25445, P25446, Q63199, Q9BDN0, Q9BDN4

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
TNFSF10	up-regulates	TNFRSF10B	binding
TP53	“up-regulates quantity by expression”	TNFRSF10B	“transcriptional regulation”
YY1	“down-regulates quantity by repression”	TNFRSF10B	“transcriptional regulation”
RNF183	“down-regulates quantity by destabilization”	TNFRSF10B	polyubiquitination
TNFRSF10B	up-regulates	FADD	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RIPK1-mediated regulated necrosis	5	29.7×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
transmembrane transport	7	11.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	49
Likely benign	17
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
6194	NM_003842.5(TNFRSF10B):c.1150_1151dup (p.Met385fs)	Pathogenic
3067904	NM_003842.5(TNFRSF10B):c.598del (p.Ser200fs)	Likely pathogenic

SpliceAI

1808 predictions. Top by Δscore:

Variant	Effect	Δscore
8:23024181:CACT:C	donor_loss	1.0000
8:23024182:ACTTA:A	donor_loss	1.0000
8:23024184:TT:T	donor_loss	1.0000
8:23024185:T:TC	donor_loss	1.0000
8:23024186:A:AC	donor_gain	1.0000
8:23024186:ACT:A	donor_gain	1.0000
8:23024186:ACTCT:A	donor_gain	1.0000
8:23024187:C:CT	donor_gain	1.0000
8:23024187:CT:C	donor_gain	1.0000
8:23024187:CTC:C	donor_gain	1.0000
8:23024187:CTCT:C	donor_gain	1.0000
8:23024187:CTCTC:C	donor_gain	1.0000
8:23024259:TCCT:T	acceptor_loss	1.0000
8:23024260:CCT:C	acceptor_loss	1.0000
8:23024261:CTGT:C	acceptor_loss	1.0000
8:23024262:T:A	acceptor_loss	1.0000
8:23027128:CT:C	donor_loss	1.0000
8:23027129:TCACC:T	donor_loss	1.0000
8:23027130:C:CG	donor_loss	1.0000
8:23027131:ACCA:A	donor_loss	1.0000
8:23027132:C:CT	donor_loss	1.0000
8:23027132:CCAG:C	donor_gain	1.0000
8:23027285:AGCT:A	acceptor_gain	1.0000
8:23027286:GCT:G	acceptor_gain	1.0000
8:23027287:CT:C	acceptor_gain	1.0000
8:23027287:CTC:C	acceptor_gain	1.0000
8:23027288:TCT:T	acceptor_gain	1.0000
8:23027289:C:CA	acceptor_loss	1.0000
8:23027289:C:CC	acceptor_gain	1.0000
8:23027300:C:CT	acceptor_gain	1.0000

AlphaMissense

2848 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:23029654:G:C	F144L	0.995
8:23029654:G:T	F144L	0.995
8:23029656:A:G	F144L	0.995
8:23022829:A:G	W389R	0.987
8:23022829:A:T	W389R	0.987
8:23029670:C:G	C139S	0.986
8:23029671:A:T	C139S	0.986
8:23029700:C:G	C129S	0.984
8:23029701:A:T	C129S	0.984
8:23029676:C:G	C137S	0.982
8:23029677:A:T	C137S	0.982
8:23022827:C:A	W389C	0.980
8:23022827:C:G	W389C	0.980
8:23022710:G:C	F428L	0.979
8:23022710:G:T	F428L	0.979
8:23022712:A:G	F428L	0.979
8:23029655:A:C	F144C	0.978
8:23029699:G:C	C129W	0.977
8:23029701:A:G	C129R	0.976
8:23030785:C:G	C113S	0.974
8:23030786:A:T	C113S	0.974
8:23043146:C:G	C81S	0.974
8:23043147:A:T	C81S	0.974
8:23029700:C:T	C129Y	0.973
8:23022932:C:A	W354C	0.972
8:23022932:C:G	W354C	0.972
8:23030767:C:G	C119S	0.972
8:23030768:A:T	C119S	0.972
8:23030776:C:G	C116S	0.972
8:23030777:A:T	C116S	0.972

dbSNP variants (sampled 300 via entrez): RS1000055290 (8:23054801 G>A), RS1000057712 (8:23045027 C>T), RS1000100410 (8:23050307 CT>C), RS1000114235 (8:23038634 C>T), RS1000178770 (8:23023409 G>A), RS1000252443 (8:23023198 C>T), RS1000346663 (8:23055816 C>G,T), RS1000356890 (8:23065738 A>C,G), RS1000384019 (8:23040080 C>G,T), RS1000425919 (8:23034722 C>A), RS1000434269 (8:23041070 T>A,C,G), RS1000526098 (8:23024834 T>A,C,G), RS1000569054 (8:23044433 A>C,T), RS1000611757 (8:23060007 C>G,T), RS1000662067 (8:23041033 T>C)

Disease associations

OMIM: gene MIM:603612 | disease phenotypes: MIM:275355

GenCC curated gene-disease

Disease	Classification	Inheritance
head and neck squamous cell carcinoma	Limited	Autosomal dominant

Mondo (1): head and neck squamous cell carcinoma (MONDO:0010150)

Orphanet (1): Squamous cell carcinoma of head and neck (Orphanet:67037)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002860	Squamous cell carcinoma

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004710_4	Renal cell carcinoma	6.000000e-09
GCST006585_2594	Blood protein levels	4.000000e-08
GCST006585_668	Blood protein levels	8.000000e-06
GCST90000015_15	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	6.000000e-06
GCST90002390_598	Mean corpuscular hemoglobin	2.000000e-15
GCST90002392_571	Mean corpuscular volume	1.000000e-12
GCST90002393_564	Monocyte count	2.000000e-12
GCST90002394_322	Monocyte percentage of white cells	1.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0600011	Parkinson’s disease symptom measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075153 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
tigatuzumab	Agonist	8.52	pKd
TRAIL	Agonist	7.23	pKd

Binding affinities (BindingDB)

181 measured of 329 human assays (354 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(E)-1-phenyl-3-phenylazanyl-prop-2-en-1-one	EC50	59 nM
2-(5-bromanylthiophen-2-yl)imidazo[1,2-a]pyridine	EC50	94 nM
3-(2-methyl-6-phenylthieno[2,3-d]pyrimidin-4-yl)sulfanylpropanoic acid	IC50	212 nM
4-fluoro-N-indan-5-yl-benzamide	EC50	217 nM
MLS001033481	EC50	250 nM
SMR000415593	EC50	310 nM
7-amino-3-phenyl-6-pyrazolo[1,5-a]pyrimidinecarboxylic acid ethyl ester	EC50	356 nM
3-(5-methyl-1,3-benzoxazol-2-yl)aniline	EC50	660 nM
MLS000115086	EC50	685 nM
(2Z)-2-(3-methyl-1,3-benzothiazol-2-ylidene)-1-(2-thienyl)ethanone	EC50	685 nM
3-(ethylthio)-6-(4-methylphenyl)pyridazine	EC50	690 nM
MLS000581513	EC50	702 nM
MLS000114722	EC50	820 nM
5-(4-ethoxyphenyl)-3-(3-pyridinyl)-1,2,4-oxadiazole	EC50	906 nM
(2Z)-1-(2,4-dihydroxyphenyl)-2-(1H-quinolin-2-ylidene)ethanone	EC50	954 nM
4-[4-(1-benzofuran-2-yl)-1,3-thiazol-2-yl]morpholine	EC50	966 nM
3-[2-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,3-thiazol-4-yl]chromen-2-one	IC50	1090 nM
(E)-3-(2-chlorophenyl)-N-(3-hydroxyphenyl)-2-propenamide	EC50	1120 nM
3-(benzenesulfonyl)-N-[4-(1,3-benzothiazol-2-yl)phenyl]propanamide	EC50	1140 nM
(E)-3-(3-hydroxyanilino)-1-(4-methoxyphenyl)-2-propen-1-one	EC50	1230 nM
MLS000680762	EC50	1230 nM
3-(4-fluorophenyl)-7-(4-pyridinyl)pyrazolo[1,5-a]pyrimidine	EC50	1240 nM
3-amino-6-(3-pyridinyl)-2-thieno[2,3-b]pyridinecarboxylic acid ethyl ester	EC50	1350 nM
2-(1,3-benzodioxol-5-yl)-5-(2-chlorophenyl)-1,3,4-oxadiazole	EC50	1410 nM
2-(4-fluoroanilino)-4-keto-4-phenyl-butyric acid	EC50	1500 nM
cid_6411701	EC50	1650 nM
SMR001275762	EC50	1660 nM
4-[[2-(1-methyl-2-pyrrolyl)-1,2-dioxoethyl]amino]benzoic acid methyl ester	EC50	1710 nM
(6E)-6-(3-phenyl-3-isoxazolin-5-ylidene)cyclohexa-2,4-dien-1-one	EC50	1780 nM
cid_3121251	EC50	1870 nM
(Z)-1-phenyl-3-(2-pyridinylamino)-2-propen-1-one	EC50	2010 nM
4-cyano-3-methyl-5-[(2-phenylquinoline-4-carbonyl)amino]thiophene-2-carboxylic acid methyl ester	IC50	2080 nM
N-(2-methoxyethyl)-2-(4-phenylphenyl)quinoline-4-carboxamide	EC50	2090 nM
MLS000100791	EC50	2330 nM
4-(4-phenylphenyl)-1,3-thiazol-2-amine	EC50	2420 nM
4-Methyl-5-phenyl-thiophene-3-carboxylic acid (3-nitro-phenyl)-amide	EC50	2440 nM
2-[(E)-2-(4-methylsulfanylphenyl)ethenyl]quinolin-8-ol	EC50	2490 nM
MLS000061602	EC50	2500 nM
1-[1-(2-methoxyethyl)-2,5-dimethyl-1H-pyrrol-3-yl]-2-[(5-methyl-1,3,4-thiadiazol-2-yl)thio]ethanone	IC50	2550 nM
2-[(4-fluorophenyl)carbamoylamino]-4-methyl-thiazole-5-carboxylic acid ethyl ester	EC50	2670 nM
2-(2,4-dimethylphenyl)-1,3-benzoxazol-5-amine	EC50	2680 nM
MLS002701727	EC50	2800 nM
MLS000416319	EC50	3080 nM
4-(5-Amino-benzooxazol-2-yl)-benzoic acid methyl ester	EC50	3090 nM
(6-methoxypyrimidin-4-yl)-(p-anisylideneamino)amine	EC50	3100 nM
1-[(3-methyl-1-benzofuran-2-yl)carbonyl]indoline	EC50	3370 nM
4-(5-methyl-3-phenyl-7-pyrazolo[1,5-a]pyrimidinyl)morpholine	EC50	3570 nM
5-(4-methylphenyl)-N-phenyl-1,3,4-oxadiazol-2-amine	IC50	3650 nM
SMR000174332	EC50	3670 nM
MLS000581623	IC50	3810 nM

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	Kd	0.05	nM	CHEMBL6189995
9.94	Kd	0.114	nM	CHEMBL6191021
9.27	Kd	0.539	nM	CHEMBL6193226
9.06	Kd	0.88	nM	CHEMBL6190032
8.91	Kd	1.24	nM	CHEMBL6189475
8.64	Kd	2.29	nM	CHEMBL6189753
8.04	Kd	9.1	nM	CHEMBL6191278
5.92	Kd	1200	nM	CHEMBL6190547

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects cotreatment, increases expression, increases response to substance, decreases expression, decreases response to substance (+4 more)	12
Bortezomib	increases activity, increases reaction, decreases degradation, decreases expression, increases localization (+7 more)	11
Resveratrol	affects reaction, decreases reaction, increases reaction, increases localization, increases response to substance (+2 more)	11
Arsenic Trioxide	increases activity, increases reaction, affects reaction, decreases reaction, affects response to substance (+2 more)	10
Acetylcysteine	increases expression, decreases expression, decreases reaction	8
Doxorubicin	affects binding, decreases reaction, increases expression, increases reaction, affects cotreatment (+2 more)	8
sodium arsenite	increases reaction, affects cotreatment, affects localization, increases abundance, increases localization (+5 more)	7
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression	7
Quercetin	increases expression, affects reaction, affects cotreatment, affects localization, increases reaction (+2 more)	7
Arsenic	affects expression, affects binding, affects cotreatment, increases expression, increases methylation (+3 more)	6
pyrazolanthrone	increases expression, affects cotreatment, decreases reaction	5
Curcumin	decreases expression, increases response to substance, increases reaction, affects cotreatment, increases expression (+1 more)	5
Fluorouracil	increases cleavage, increases reaction, affects cotreatment, decreases expression, decreases response to substance (+2 more)	5
Particulate Matter	increases expression, affects expression, increases reaction, increases abundance	5
trichostatin A	affects reaction, increases expression, affects expression, affects cotreatment	4
sulindac sulfide	decreases expression, decreases reaction, increases expression	4
Vorinostat	affects cotreatment, affects reaction, increases expression, increases reaction	4
Methotrexate	increases expression, decreases expression	4
Plant Extracts	affects cotreatment, increases expression, decreases reaction, increases reaction	4
bisphenol A	affects expression, increases expression, affects cotreatment	3
cobaltous chloride	affects binding, decreases reaction, increases expression, increases reaction, affects expression	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases expression, increases reaction	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	3
Cycloheximide	decreases reaction, increases expression, increases reaction, affects cotreatment, increases localization (+1 more)	3
Dactinomycin	affects response to substance, decreases expression, decreases reaction, increases expression	3
Ozone	affects expression, increases abundance, affects cotreatment, increases expression	3
Tunicamycin	increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
Cyclosporine	increases expression	3
Genistein	decreases reaction, increases expression, decreases expression	3

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069762	Binding	Induction of DR5 receptor promotor activity in human DLD1 cells co-transfected with Sac1 cells at 18.5 uM after 24 hrs by luciferase assay	Death receptor 5 promoter-enhancing compounds isolated from Catimbium speciosum and their enhancement effect on TRAIL-induced apoptosis. — Bioorg Med Chem

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2J2	Abcam HeLa TNFRSF10B KO	Cancer cell line	Female
CVCL_B7ZZ	Abcam Raji TNFRSF10B KO	Cancer cell line	Male
CVCL_C0AT	Abcam THP-1 TNFRSF10B KO	Cancer cell line	Male
CVCL_C7CG	Abcam PC-3 TNFRSF10B KO	Cancer cell line	Male
CVCL_D8XA	Ubigene HCT 116 TNFRSF10B KO	Cancer cell line	Male
CVCL_KU13	HeLa SilenciX TRAILR2	Cancer cell line	Female
CVCL_TT06	HAP1 TNFRSF10B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01344356	PHASE4	COMPLETED	Stereotactic Body Radiotherapy for Head and Neck Tumors
NCT03196843	PHASE4	UNKNOWN	Radiotherapy Combine With Raltitrexed Versus Radiotherapy Alone in Older Patients With HNSCC.
NCT03998696	PHASE4	COMPLETED	An Experimental Study to Compare Treatment Response and Toxicities of Concurrent Chemoradiation With Weekly Cisplatin and Three Weekly Cisplatin in Locally Advanced Head and Neck Cancer.
NCT04489888	PHASE4	COMPLETED	A Study of Pembrolizumab (MK-3475) Plus Carboplatin and Paclitaxel as First-line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (MK-3475-B10/KEYNOTE B10)
NCT04766827	PHASE4	UNKNOWN	Albumin-bound Paclitaxel Combined With Cisplatin Versus Docetaxel Combined With Cisplatin Induced Chemotherapy in Advanced Head and Neck Squamous Tummor
NCT06162377	PHASE4	RECRUITING	Methylnatrexone In Resectable Head and Neck Squamous Cell Carcinoma (MINK). A Window of Opportunity Pilot Study.
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00050388	PHASE3	COMPLETED	Phase II Trial of Allovectin-7® for Head and Neck Cancer
NCT00174837	PHASE3	COMPLETED	TRACE: Tirapazamine-Radiation And Cisplatin Evaluation
NCT00206219	PHASE3	COMPLETED	Head and Neck Phase III Iressa Versus Methotrexate Refractory: Iressa Versus Methotrexate (IMEX)
NCT00442455	PHASE3	COMPLETED	Erlotinib,Radiation and Cisplatin in Patients With Complete Resected Squamous Cell Carcinoma of the Head and Neck
NCT00609284	PHASE3	COMPLETED	Randomized Trial of Concomitant Chemotherapy in Patients With Locally Advanced HNSCC Treated by Radiotherapy-erbitux
NCT00911326	PHASE3	TERMINATED	Evaluation of Sentinel Lymph Nodes in Head and Neck Squamous Cell Carcinoma
NCT00999700	PHASE3	UNKNOWN	Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin
NCT01012258	PHASE3	COMPLETED	Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects
NCT01086826	PHASE3	COMPLETED	Treatment of Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
NCT01177956	PHASE3	COMPLETED	A Trial to Determine the Safety and Anti-tumor Activity Profile of the Combination of Cetuximab and Concomitant Cisplatin Plus 5-Fluorouracil (5-FU) in Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma in Head and Neck
NCT01427478	PHASE3	COMPLETED	Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck
NCT01864850	PHASE3	COMPLETED	Non Inferiority Trial of Standard RT Versus Hypofractionated Split Course in Elderly Vulnerable Patients With HNSCC
NCT01931150	PHASE3	COMPLETED	Study of Prophylactic Topical Dapsone 5% Gel Versus Moisturizer for Cetuximab-induced Papulopustular (Acneiform) Rash in Patients With mCRC or HNSCC Without Previous or Concurrent RT
NCT01950689	PHASE3	COMPLETED	NIMRAD (A Randomised Placebo-controlled Trial of Synchronous NIMorazole Versus RADiotherapy Alone in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Not Suitable for Synchronous Chemotherapy or Cetuximab)
NCT02105636	PHASE3	COMPLETED	Trial of Nivolumab vs Therapy of Investigator’s Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)
NCT02551159	PHASE3	COMPLETED	Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer
NCT02661152	PHASE3	UNKNOWN	DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC.
NCT02715596	PHASE3	COMPLETED	Changes in Body Composition After EPA Supplementation in Head and Neck Patients
NCT02952586	PHASE3	TERMINATED	Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)
NCT02998385	PHASE3	ACTIVE_NOT_RECRUITING	Chemo-radiotherapy Versus Radiotherapy in the Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy)
NCT02999087	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)
NCT03340896	PHASE3	ACTIVE_NOT_RECRUITING	Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT
NCT03349710	PHASE3	COMPLETED	Nivolumab or Nivolumab Plus Cisplatin, in Combination With Radiotherapy in Patients With Cisplatin-ineligible or Eligible Locally Advanced Squamous Cell Head and Neck Cancer
NCT03519048	PHASE3	ACTIVE_NOT_RECRUITING	Multicentric Comparative Study Between a Conventional and an Intensive Follow up Strategy After Treatment of a Head and Neck Squamous Cell Carcinoma
NCT03576417	PHASE3	ACTIVE_NOT_RECRUITING	A Trial Evaluating the Addition of Nivolumab to Cisplatin-RT for Treatment of Cancers of the Head and Neck
NCT03855384	PHASE3	UNKNOWN	Study of TQB2450 in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck（R/M SCCHN）
NCT04146402	PHASE3	UNKNOWN	SCT-I10A Plus Standard Chemotherapy in First-line Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma
NCT04157985	PHASE3	COMPLETED	Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
NCT04199104	PHASE3	COMPLETED	A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (MK-7902-010) (KEYNOTE-010)
NCT04459715	PHASE3	TERMINATED	A Study of Xevinapant (Debio 1143) in Combination With Platinum-Based Chemotherapy and Standard Fractionation Intensity-Modulated Radiotherapy in Participants With Locally Advanced Squamous Cell Carcinoma of the Head and Neck, Suitable for Definitive Chemoradiotherapy (TrilynX)
NCT04590963	PHASE3	ACTIVE_NOT_RECRUITING	Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer
NCT04747054	PHASE3	RECRUITING	Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers
NCT04780750	PHASE3	UNKNOWN	Concurent Chemoradiotherapy in Head and Neck Cancers