Highlight
- Identification of rare, damaging BIRC3 variants in patients with monogenic Crohn’s disease (CD) across ages.
- BIRC3 deficiency disrupts receptor-interacting protein kinase 1 (RIPK1) ubiquitylation, leading to increased intestinal epithelial cell death through autophosphorylation of RIPK1.
- Functional and transcriptomic analyses in cellular, mouse, and zebrafish models demonstrate dysregulated TNF signaling and spontaneous intestinal inflammation due to BIRC3 variants.
- Pharmacological inhibition of RIPK1 or caspases mitigates intestinal inflammation, highlighting RIPK1 as a viable therapeutic target in BIRC3-deficient CD.
Study Background
Specialty calculators
For clinical reference; use professional judgment.
