TNFRSF12A
Chr 16TNF receptor superfamily member 12A
Also known as: CD266, FN14, TWEAKR
The TNFRSF12A protein functions as a receptor for TNFSF12/TWEAK and regulates apoptosis, angiogenesis, endothelial cell proliferation, and wound healing. Mutations cause Opitz GBBB syndrome type 2, an X-linked disorder characterized by developmental abnormalities affecting multiple organ systems including craniofacial features, cardiac defects, and genitourinary anomalies. The gene shows tolerance to loss-of-function variants (pLI 0.018, LOEUF 1.53), suggesting haploinsufficiency may not be the primary disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is gain-of-function.
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
TNFRSF12A · 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