JAG1

Chr 20AD

jagged canonical Notch ligand 1

Also known as: AGS, AGS1, AHD, AWS, CD339, CMT2HH, DCHE, HJ1

NCBI Gene: 182 ENSG00000101384 UniProt: P78504 OMIM: 601920

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).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter is involved in signaling processes. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis. [provided by RefSeq, Nov 2019]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Deafness, congenital heart defects, and posterior embryotoxonMIM #617992

Alagille syndrome 1MIM #118450

Charcot-Marie-Tooth disease, axonal, type 2HHMIM #619574

Tetralogy of FallotMIM #187500

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

176

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.15

LOEUF· LoF intol.

LOF

Mechanism· G2P

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