TNFRSF10B

Chr 8

TNF receptor superfamily member 10b

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

NCBI Gene: 8795 ENSG00000120889 UniProt: O14763

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSquamous cell carcinoma of the head and neck

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in TNFRSF10B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

621 rare PASS variants

Rare truncating (LoF)

1 in 400

109 rare PASS variants

Rare synonymous (reference)

1 in 200

239 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TNFRSF10B; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 360
South Asian	~43k	1 in 150	1 in 510
Remaining (unassigned)	~30k	1 in 86	1 in 390
European (Finnish)	~27k	1 in 610	1 in 1,800
Admixed American	~22k	1 in 88	1 in 500
African / African American	~21k	1 in 86	1 in 910
East Asian	~20k	1 in 94	≈ 1 in 4,000
Ashkenazi Jewish	~13k	1 in 650	none seen
Middle Eastern	~2,884	1 in 83	1 in 480

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓