TNFRSF10D

Chr 8

TNF receptor superfamily member 10d

Also known as: CD264, DCR2, TRAIL-R4, TRAILR4, TRUNDD

NCBI Gene: 8793ENSG00000173530UniProt: Q9UBN6

The protein is a TNF-receptor superfamily member that binds TRAIL ligand and protects cells from TRAIL-mediated apoptosis through its truncated cytoplasmic death domain. The gene is highly intolerant to loss-of-function variants (pLI ~0, LOEUF 1.17), but no human disease associations have been established for TNFRSF10D mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
82
P/LP submissions
0%
P/LP missense
1.17
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— TNFRSF10D
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 63 VUS of 169 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 1.01
OE 0.75 (0.49–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.01Z-score
OE missense 1.00 (0.90–1.12)
218 obs / 217.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.75 (0.49–1.17)
0≤0.351.4
Missense OE1.00 (0.90–1.12)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 14 / 18.7Missense obs/exp: 218 / 217.6Syn Z: 0.40
DN
0.6745th %ile
GOF
0.80top 10%
LOF
0.2970th %ile

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.

GOFprediction above median
DNprediction above median

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

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic78
Likely Pathogenic4
VUS63
Likely Benign10
Benign4
78
Pathogenic
4
Likely Pathogenic
63
VUS
10
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
78
0
78
Likely Pathogenic
0
0
4
0
4
VUS
0
59
4
0
63
Likely Benign
0
9
1
0
10
Benign
0
3
0
1
4
Total071871159

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TNFRSF10D · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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