TNFRSF10B
Chr 8ARTNF receptor superfamily member 10b
Also known as: CD262, DR5, KILLER, KILLER/DR5, TRAIL-R2, TRAILR2, TRICK2, TRICK2A
This protein is a tumor necrosis factor receptor superfamily member that contains an intracellular death domain and transduces apoptosis signals when activated by TRAIL ligand, recruiting FADD and caspase-8 to initiate programmed cell death cascades. Mutations cause squamous cell carcinoma of the head and neck with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (low pLI score), suggesting that complete loss of function may be required for disease manifestation.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
188 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 78 | 0 | 79 |
Likely Pathogenic | 1 | 0 | 4 | 0 | 5 |
VUS | 0 | 54 | 6 | 0 | 60 |
Likely Benign | 0 | 7 | 4 | 8 | 19 |
Benign | 0 | 3 | 1 | 0 | 4 |
| Total | 2 | 64 | 93 | 8 | 167 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TNFRSF10B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers
RECRUITINGTesting the Addition of an Anti-Cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (5-Fluorouracil) for Metastatic, Refractory Colorectal Cancer
RECRUITINGTRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer
NOT YET RECRUITINGEffect of Low-Level Light Therapy on Ocular Surface Parameters in Patients With Graves Disease
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools