TNFRSF21

Chr 6

TNF receptor superfamily member 21

Also known as: BM-018, CD358, DR6

NCBI Gene: 27242ENSG00000146072UniProt: O75509

This gene encodes a member of the tumor necrosis factor receptor superfamily. The encoded protein activates nuclear factor kappa-B and mitogen-activated protein kinase 8 (also called c-Jun N-terminal kinase 1), and induces cell apoptosis. Through its death domain, the encoded receptor interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD) protein, which is known to mediate signal transduction of tumor necrosis factor receptors. Knockout studies in mice suggest that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. [provided by RefSeq, Jul 2013]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
27
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.61
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?
0.61LOEUF
pLI 0.041
Z-score 2.84
OE 0.31 (0.17–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.22Z-score
OE missense 0.82 (0.75–0.90)
304 obs / 369.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.31 (0.17–0.61)
0≤0.351.4
Missense OE?0.82 (0.75–0.90)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 6 / 19.6Missense obs/exp: 304 / 369.8Syn Z: -0.29

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TNFRSF21 · 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 →

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