TNFRSF10B Gene (TNF Receptor Superfamily Member 10b)
Key mediator of extrinsic apoptosis and cancer signaling
Gene Information Card
| Symbol | TNFRSF10B |
|---|---|
| Full Name | TNF Receptor Superfamily Member 10b |
| Gene Type | protein-coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 8795 ncbi.nlm.nih.gov/gene/8795 |
| Ensembl ID | ENSG00000120889 |
| UniProt ID | O14763 |
| OMIM ID | 603612 |
| HGNC ID | 11905 |
| Aliases | DR5, TRAIL-R2, TRICK2, KILLER, CD262 |
Description
TNFRSF10B (TNF Receptor Superfamily Member 10b), also known as DR5 or TRAIL-R2, is a cell surface receptor that binds TRAIL (TNFSF10) and mediates apoptosis. It contains a cytoplasmic death domain and activates caspase cascade upon ligand binding. The gene is located on chromosome 8p21.3 and is frequently altered in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Loss of heterozygosity or promoter methylation reduces DR5 expression, impairing TRAIL-induced apoptosis | PMID: 15696293; COSMIC |
| Non-Small Cell Lung Cancer | Somatic mutations in the death domain disrupt TRAIL signaling | PMID: 17699752; COSMIC |
| Head and Neck Squamous Cell Carcinoma | Frequent copy number loss and reduced DR5 expression correlate with poor prognosis | PMID: 21746838; COSMIC |
| Breast Cancer | Epigenetic silencing of TNFRSF10B via promoter hypermethylation | PMID: 19029981; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 8.2 | Medium |
| Spleen | 6.5 | Medium |
| Lung | 4.1 | Low |
| Colon | 3.8 | Low |
| Breast | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.5 | Cervical cancer cell line |
| A549 | 9.8 | Lung adenocarcinoma |
| HCT116 | 8.3 | Colorectal carcinoma |
| MCF7 | 5.1 | Breast cancer |
| K562 | 4.2 | Chronic myeloid leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1135C>T (p.Arg379*) | Nonsense | <1% | Truncated protein, loss of death domain |
| c.1138G>A (p.Gly380Arg) | Missense | <1% | Impaired TRAIL binding and apoptosis |
| c.1142T>C (p.Leu381Pro) | Missense | <1% | Disrupts death domain structure |
| c.1150A>G (p.Asn384Asp) | Missense | <1% | Reduced caspase-8 activation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations in the death domain (e.g., p.Arg379*, p.Gly380Arg) impair TRAIL-induced apoptosis, acting as loss-of-function alleles.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TNFRSF10B.
Dominant Negative (DN)
Truncated receptors lacking the death domain can oligomerize with wild-type DR5 and block signaling, acting as dominant-negative inhibitors.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TRAIL Signaling Pathway (Reactome: R-HSA-75108)
• Apoptosis (KEGG: hsa04210)
• NF-kappa B Signaling (KEGG: hsa04064)
• p53-Independent DNA Damage Response (WikiPathways: WP707)
Protein Summary
TNFRSF10B (DR5) is a 411-amino acid type I transmembrane protein with two extracellular cysteine-rich domains and a cytoplasmic death domain. It forms homotrimers upon TRAIL binding, recruiting FADD and procaspase-8 to form the death-inducing signaling complex (DISC), leading to caspase cascade activation and apoptosis. DR5 also activates NF-κB and JNK pathways. The protein is expressed in many tissues and is frequently downregulated in cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF10B Knockout HEK293 Cell Line | EDJ-KQ6368 | Human | 8795 | Details Get a Quote |
| TNFRSF10B Knockout A-549 Cell Line | EDJ-KQ30342 | Human | 8795 | Details Get a Quote |
| TNFRSF10B Knockout HCT 116 Cell Line | EDJ-KQ30343 | Human | 8795 | Details Get a Quote |
| TNFRSF10B Knockout HeLa Cell Line | EDJ-KQ30344 | Human | 8795 | Details Get a Quote |
| Tnfrsf10b Knockout MC-38 Cell Line | EDJ-KZ514 | Mouse | 8795 | Details Get a Quote |
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