TNFRSF6B

Chr 20

TNF receptor superfamily member 6b

Also known as: DCR3, DJ583P15.1.1, M68, M68E, TR6

NCBI Gene: 8771ENSG00000243509UniProt: O95407OMIM: 603361

The encoded protein functions as a decoy receptor that neutralizes cytotoxic ligands including FASL and LIGHT, thereby protecting cells against apoptosis. This gene is extremely tolerant to loss-of-function variants (pLI near 0, LOEUF 1.77), and no Mendelian diseases have been definitively associated with TNFRSF6B mutations in pediatric patients.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.77
Clinical Summary— TNFRSF6B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 101 VUS of 161 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
1.77LOEUF
pLI 0.000
Z-score -0.15
OE 1.06 (0.61–1.77)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.30Z-score
OE missense 1.26 (1.13–1.40)
250 obs / 198.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.06 (0.61–1.77)
0≤0.351.4
Missense OE1.26 (1.13–1.40)
0≤0.61.4
Synonymous OE1.59
0≤1.21.6
LoF obs/exp: 8 / 7.6Missense obs/exp: 250 / 198.6Syn Z: -4.41
DN
0.6454th %ile
GOF
0.7028th %ile
LOF
0.3356th %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

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic8
VUS101
Likely Benign12
Benign10
Conflicting3
27
Pathogenic
8
Likely Pathogenic
101
VUS
12
Likely Benign
10
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
8
0
8
VUS
7
81
12
1
101
Likely Benign
0
1
1
10
12
Benign
0
0
1
9
10
Conflicting
—3
Total7824920161

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

View in ClinVar →

Protein Context — Lollipop Plot

TNFRSF6B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Evolutionary and molecular characterization of fish specific decoy receptor 3 isoforms (TNFRSF6B.1 and 2) in rock bream (Oplegnathus fascatus).
Ko S et al.·Dev Comp Immunol
2025
ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients.
Huang Y et al.·Transl Oncol
2025Open AccessCohort
Discovery of a Novel Shared Variant Among RTEL1 Gene and RTEL1-TNFRSF6B lncRNA at Chromosome 20q13.33 in Familial Progressive Myoclonus Epilepsy.
Chaudhari S et al.·Int J Genomics
2024Open Access
Integrative analysis of TNFRSF6B as a potential therapeutic target for pancreatic cancer.
Zhang C et al.·J Gastrointest Oncol
2021
Case-Control Study on TNFRSF6B Gene Polymorphism and Susceptibility to Gastric Cancer in a Chinese Han Population.
Gu X et al.·Pharmgenomics Pers Med
2020Open Access
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