TNFSF15
Chr 9TNF superfamily member 15
The protein functions as a TNF ligand family cytokine that binds to receptors TNFRSF25 and TNFRSF6B, activates NF-kappaB signaling, and regulates endothelial cell apoptosis and angiogenesis inhibition. Based on the low pLI score (0.003) and high LOEUF score (0.95), this gene appears highly tolerant to loss-of-function mutations, and no established Mendelian diseases have been definitively linked to TNFSF15 mutations in the pediatric population. The predicted dominant-negative mechanism suggests potential pathogenicity through protein interference rather than haploinsufficiency.
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TNFSF15 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools