TNFRSF10A Gene - TRAIL Receptor 1 (DR4)
Key regulator of extrinsic apoptosis and cancer signaling
Gene Information Card
| Symbol | TNFRSF10A |
|---|---|
| Full Name | TNF Receptor Superfamily Member 10a |
| Gene Type | protein-coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 8797 ncbi.nlm.nih.gov/gene/8797 |
| Ensembl ID | ENSG00000104689 |
| UniProt ID | O00220 |
| OMIM ID | 603611 |
| HGNC ID | 11904 |
| Aliases | DR4, TRAILR1, APO2, CD261, TRAIL-R1 |
Description
TNFRSF10A encodes death receptor 4 (DR4), a member of the TNF-receptor superfamily. DR4 is a receptor for TRAIL (TNFSF10) and mediates apoptosis via the extrinsic pathway. It contains a cytoplasmic death domain that recruits FADD and caspase-8 upon ligand binding. The gene is located on chromosome 8p21.3 and is implicated in cancer, autoimmune disorders, and infectious diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Loss of DR4 expression or function reduces TRAIL-induced apoptosis, promoting tumor survival | ClinVar, COSMIC, literature |
| Head and neck squamous cell carcinoma | Somatic mutations in TNFRSF10A impair death receptor signaling | COSMIC, PMID: 15696293 |
| Non-small cell lung cancer | Reduced DR4 expression correlates with poor prognosis | NCBI Gene, PMID: 19165229 |
| Autoimmune lymphoproliferative syndrome (ALPS) | Germline mutations in TNFRSF10A disrupt apoptosis of lymphocytes | OMIM, PMID: 20094047 |
| Colorectal cancer | TNFRSF10A polymorphisms associated with increased risk | ClinVar, PMID: 21573174 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 5.2 | Medium |
| Spleen | 4.8 | Medium |
| Lung | 3.1 | Low |
| Liver | 2.5 | Low |
| Kidney | 2.0 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 6.5 | High expression |
| HeLa | 4.0 | Moderate expression |
| A549 | 3.8 | Moderate expression |
| MCF7 | 2.1 | Low expression |
| Jurkat | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.626A>G (p.Tyr209Cys) | Missense | <0.01 | Reduced TRAIL binding and apoptosis |
| c.1135C>T (p.Arg379*) | Nonsense | <0.01 | Truncated protein, loss of death domain |
| c.1A>G (p.Met1Val) | Missense | <0.01 | Start codon loss, no protein |
| c.1069_1070del (p.Leu357fs) | Frameshift | <0.01 | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense, nonsense, and frameshift mutations that impair TRAIL binding or death domain function reduce apoptosis.
Gain of Function (GOF)
Not reported in TNFRSF10A; gain-of-function is rare for death receptors.
Dominant Negative (DN)
Truncated receptors lacking the death domain can interfere with wild-type DR4 signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TRAIL signaling pathway (KEGG hsa04668)
• Apoptosis (KEGG hsa04210)
• TNF signaling pathway (KEGG hsa04668)
• Extrinsic pathway for apoptosis (Reactome R-HSA-109581)
Protein Summary
DR4 (TNFRSF10A) is a 468-amino acid type I transmembrane protein with two extracellular cysteine-rich domains and a cytoplasmic death domain. It binds TRAIL (TNFSF10) and recruits FADD and caspase-8 to form the death-inducing signaling complex (DISC), leading to caspase cascade activation and apoptosis. DR4 is widely expressed in normal tissues but frequently downregulated or mutated in cancers, contributing to TRAIL resistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF10A Knockout HEK293 Cell Line | EDJ-KQ5665 | Human | 8797 | Details Get a Quote |
| TNFRSF10A Knockout A-549 Cell Line | EDJ-KQ30325 | Human | 8797 | Details Get a Quote |
| TNFRSF10A Knockout HCT 116 Cell Line | EDJ-KQ30327 | Human | 8797 | Details Get a Quote |
| TNFRSF10A Knockout HeLa Cell Line | EDJ-KQ30328 | Human | 8797 | Details Get a Quote |
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