TNFRSF11B

Chr 8AR

TNF receptor superfamily member 11b

Also known as: OCIF, OPG, PDB5, TR1

NCBI Gene: 4982ENSG00000164761UniProt: O00300OMIM: 602643

The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is an osteoblast-secreted decoy receptor that functions as a negative regulator of bone resorption. This protein specifically binds to its ligand, osteoprotegerin ligand, both of which are key extracellular regulators of osteoclast development. Studies of the mouse counterpart also suggest that this protein and its ligand play a role in lymph-node organogenesis and vascular calcification. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismARLOEUF 0.551 OMIM phenotype
Clinical Summary— TNFRSF11B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
💊
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?
0.55LOEUF
pLI 0.162
Z-score 3.00
OE 0.26 (0.14–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.84Z-score
OE missense 0.84 (0.74–0.95)
184 obs / 219.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.26 (0.14–0.55)
0≤0.351.4
Missense OE?0.84 (0.74–0.95)
0≤0.61.4
Synonymous OE?0.92
0≤1.21.6
LoF obs/exp: 5 / 19.2Missense obs/exp: 184 / 219.0Syn Z: 0.57

This gene — mechanism propensity

DN
0.6745th %ile
GOF
0.74top 25%
LOF
0.2485th %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

ClinVar

Protein Context — Lollipop Plot

TNFRSF11B · protein map & ClinVar variants

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

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