TNFSF12
Chr 17TNF superfamily member 12
Also known as: APO3L, DR3LG, TNF12, TNLG4A, TWEAK
The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
305 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 | 0 | 0 | 20 | 0 | 20 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 4 | 128 | 29 | 2 | 163 |
Likely Benign | 0 | 0 | 42 | 66 | 108 |
Benign | 0 | 0 | 6 | 6 | 12 |
Conflicting | — | 1 | |||
| Total | 4 | 128 | 98 | 74 | 305 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →TNFSF12 · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Investigating the Combined Effects of Protein, Blueberries, and Exercise on Cardiovascular Health and Frailty in Older Nova Scotians
NOT YET RECRUITINGPET/MR in Post Stroke Cardiac Inflammation Study
RECRUITINGEffects of Autonomic Nervous System Modulation by Heart Rate Variability Biofeedback Training With Resonant Frequency Breathing on Glucose Metabolism in Individuals With Prediabetes
RECRUITINGExternal Resources
Links to major genomics databases and tools