JAG1
Chr 20ADjagged canonical Notch ligand 1
Also known as: AGS, AGS1, AHD, AWS, CD339, CMT2HH, DCHE, HJ1
The jagged 1 protein functions as a ligand for Notch receptors, mediating Notch signaling pathways involved in hematopoiesis, cardiovascular development, and cell-fate decisions. Mutations cause Alagille syndrome 1 (characterized by liver, heart, eye, and skeletal abnormalities), as well as congenital heart defects, deafness with posterior embryotoxon, tetralogy of Fallot, and axonal Charcot-Marie-Tooth disease type 2HH. JAG1 follows autosomal dominant inheritance and is highly constrained against loss-of-function variants (pLI >0.99).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
JAG1 · 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
Effect of Snacks on Aging
RECRUITINGPediatric Evaluation and Registry for Liver Cholestasis in Canada
RECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGExternal Resources
Links to major genomics databases and tools