TNFRSF11B
Chr 8ARTNF receptor superfamily member 11b
Also known as: OCIF, OPG, PDB5, TR1
The protein functions as a decoy receptor that inhibits bone resorption by binding to osteoprotegerin ligand and neutralizing osteoclast activation, serving as a key negative regulator of bone homeostasis. Mutations cause autosomal recessive juvenile-onset Paget disease of bone 5, characterized by early-onset abnormal bone remodeling. The gene is moderately constrained against loss-of-function variants (LOEUF 0.548), indicating some intolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
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.
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
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 4 | 0 | 18 | 0 | 22 |
Likely Pathogenic | 1 | 0 | 0 | 0 | 1 |
VUS | 3 | 104 | 6 | 0 | 113 |
Likely Benign | 0 | 0 | 16 | 31 | 47 |
Benign | 0 | 0 | 1 | 1 | 2 |
| Total | 8 | 104 | 41 | 32 | 185 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
The Bone-parathyroid Crosstalk in Primary Hyperparathyroidism
NOT YET RECRUITINGRenal and Vascular Phenotypic Characterization of Patients With Enamel Renal Syndrome Due to a Pathogenic Variant of the FAM20A Gene and Pathophysiological Study of Ectopic Calcifications
NOT YET RECRUITINGDried Plums and Bone Health in Postmenopausal Women
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools