TNFRSF6B

Chr 20

TNF receptor superfamily member 6b

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

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.

Summary from RefSeq, UniProt
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1
Active trials
12
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.77
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryTNFRSF6B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.77LOEUF
pLI 0.000
Z-score -0.15
OE 1.06 (0.611.77)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.30Z-score
OE missense 1.26 (1.131.40)
250 obs / 198.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.06 (0.611.77)
00.351.4
Missense OE1.26 (1.131.40)
00.61.4
Synonymous OE1.59
01.21.6
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

0 submitted variants 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
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