TNFRSF10B

Chr 8AR

TNF receptor superfamily member 10b

Also known as: CD262, DR5, KILLER, KILLER/DR5, TRAIL-R2, TRAILR2, TRICK2, TRICK2A

NCBI Gene: 8795 ENSG00000120889 UniProt: O14763 OMIM: 603612

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Mar 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Squamous cell carcinoma, head and neckMIM #275355

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.05

OE 0.49 (0.29–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.67Z-score

OE missense 1.12 (1.01–1.24)

270 obs / 240.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.49 (0.29–0.85)

0≤0.351.4

Missense OE?1.12 (1.01–1.24)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 9 / 18.5Missense obs/exp: 270 / 240.7Syn Z: -0.22

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Metastatic Microsatellite Stable Colorectal CarcinomaRefractory Microsatellite Stable Colorectal CarcinomaStage IV Colorectal Cancer AJCC v8

Testing the Addition of an Anti-Cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (5-Fluorouracil) for Metastatic, Refractory Colorectal Cancer

RECRUITING

NCT06654037Phase PHASE1National Cancer Institute (NCI)Started 2025-04-18

AbemaciclibBiopsy ProcedureBiospecimen Collection

Metastatic Colorectal CarcinomaMetastatic Malignant Solid NeoplasmStage IV Colorectal Cancer AJCC v8

Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers

RECRUITING

NCT05803382Phase PHASE1National Cancer Institute (NCI)Started 2023-11-08

BET Bromodomain Inhibitor ZEN-3694Biopsy ProcedureBiospecimen Collection

Dry Eye Disease (DED)Graves Ophthalmopathy

Effect of Low-Level Light Therapy on Ocular Surface Parameters in Patients With Graves Disease

ENROLLING BY INVITATION

NCT07332988Phase NAGrigore T. Popa University of Medicine and PharmacyStarted 2025-08-01