ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000020.10) (NC_000020.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
9585603 Krantz et al. (1998) tested 54 Alagille syndrome (AGS) patients and their families for for the frequency of variants in JAG1. They found mutations/deletions in 75% of the patients, including 3 whole-gene deletions, 19 small deletions and insertions, and 9 nonsense mutations. Some of the identified variants were de novo and some were inherited from parents with clinical features consistent with JAG1 or an AGS microform (meaning they had some physical features consisted with AGS but not enough to establish clinical diagnosis).
12497640 Ropke et al. (2003) tested a series of probands with Alagille syndrome for mutations in JAG1. They identified 36 new variants in JAG1, including 23 truncating variants (these included deletions, insertions, complex and nonsense variants). Some of the identified variants were de novo and some were determined to be inherited.
16575836 Warthen et al. (2006) tested 247 probands with diagnosis of Alagille syndrome and found JAG1 mutations in 94% of patients, including over 40 different truncating variants.

Haploinsufficiency phenotype comments:

Haploinsufficiency of JAG1 is associated with Alagille syndrome. Alagille syndrome is an autosomal dominant disorder variably affecting multiple organ systems including the liver, heart, vertebra, kidneys, vasculature, eye and face. Genotype-phenotype correlation studies suggest deletions including JAG1 and smaller than approximately 4-5 Mb do not result in additional clinical findings as compared to patients with isolated JAG1 disruption.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No evidence supporting or refuting triplosensitivity of this gene.