TNFRSF1B

Chr 1

TNF receptor superfamily member 1B

Also known as: CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B, TNFR2, TNFR80

NCBI Gene: 7133 ENSG00000028137 UniProt: P20333 OMIM: 191191

The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.48

Clinical Summary— TNFRSF1B

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.

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ClinVar Variants

47 VUS of 66 total submissions

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Clinical Trials

2 active or recruiting trials — 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

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.502

Z-score 3.22

OE 0.21 (0.10–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.93Z-score

OE missense 0.84 (0.76–0.94)

235 obs / 278.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.10–0.48)

0≤0.351.4

Missense OE?0.84 (0.76–0.94)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 4 / 19.2Missense obs/exp: 235 / 278.7Syn Z: 0.64

This gene — mechanism propensity

0.6649th %ile

GOF

0.75top 25%

LOF

0.3843th %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

66 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign5

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	46	1	0	47
Likely Benign	1	1	3	5
Benign	4	0	1	5
Total	51	2	4	57

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap TNFRSF1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →