Activity

Filter

Cancel
Date Panel Item Activity
14 actions
Tubulointerstitial kidney disease v3.10 JAG1 Ida Ertmanska Tag Q4_25_promote_green tag was added to gene: JAG1.
Tag Q4_25_NHS_review tag was added to gene: JAG1.
Tubulointerstitial kidney disease v3.10 JAG1 Ida Ertmanska Phenotypes for gene: JAG1 were changed from tubulointersitial kidney disease; kidney failure to Autosomal dominant tubulointerstitial kidney disease
Tubulointerstitial kidney disease v3.9 JAG1 Ida Ertmanska Publications for gene: JAG1 were set to PMID: 41061854
Tubulointerstitial kidney disease v3.8 JAG1 Ida Ertmanska Mode of pathogenicity for gene: JAG1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Tubulointerstitial kidney disease v3.7 JAG1 Ida Ertmanska Classified gene: JAG1 as Amber List (moderate evidence)
Tubulointerstitial kidney disease v3.7 JAG1 Ida Ertmanska Gene: jag1 has been classified as Amber List (Moderate Evidence).
Tubulointerstitial kidney disease v3.6 JAG1 Ida Ertmanska changed review comment from: Comment on list classification: There are at least 3 unrelated individuals with monoallelic variants in JAG1 and isolated tubulointerstitial kidney disease. Based on the available evidence, this gene should be rated Green for Tubulointerstitial kidney disease.; to: Comment on list classification: There are at least 3 unrelated individuals with monoallelic variants in JAG1 and isolated tubulointerstitial kidney disease. Based on the available evidence, this gene should be rated Green for Tubulointerstitial kidney disease.
Tubulointerstitial kidney disease v3.6 JAG1 Ida Ertmanska commented on gene: JAG1: Comment on list classification: There are at least 3 unrelated individuals with monoallelic variants in JAG1 and isolated tubulointerstitial kidney disease. Based on the available evidence, this gene should be rated Green for Tubulointerstitial kidney disease.
Tubulointerstitial kidney disease v3.6 JAG1 Ida Ertmanska edited their review of gene: JAG1: Changed rating: GREEN
Tubulointerstitial kidney disease v3.6 JAG1 Ida Ertmanska changed review comment from: PMID: 41061854 Menguy et al., 2025 (in press)
Cohort of 203 families with Autosomal dominant tubulointerstitial kidney disease (ADTKD) & kidney disease cases with unknown aetiology from the 100,000 Genomes project - 1133 patients.
Variants in JAG1 were identified in three large families with unsolved ADTKD:
Family 1: c.864G>A, p.Trp288* - not in gnomAD v4.
Family 2: c.601C>T, p.Arg201Cys - MAF in gnomAD v4 = 0.000001695 (European); Revel score = 0.89.
Family 3: c.2372+3_2372+6del - not in gnomAD v4; SpliceAI score = 0.62 Splice-altering Strong.
Tubulointerstitial nephropathy was confirmed by kidney histology in 2 cases from 2 families. Variants shown to segregate with disease, with the exception of individual III-3 in Family 2, who was an asymptomatic carrier. Exome sequencing was used for families 1 & 3, and a targeted NGS panel for family 2.

Further 6 cases reported from the Necker hospital in Paris: individuals with chronic kidney disease, without proteinuria, hematuria, or uropathy. 6 rare missense variants in JAG1 were identified. Also, 2 cases from the 100,000 Genomes project were identified to harbour two different rare missense variants in JAG1. No access to supplementary material to retrieve the variant details at this time.

JAG1 expression studies & ER stress analysis suggests that the tubulointerstitial renal disease was due to haploinsufficiency and loss of function. JAG1 is predicted to be dosage sensitive with pLI = 1.

JAG1 is associated with several autosomal dominant phenotypes in OMIM: Tetralogy of Fallot, 187500; Charcot-Marie-Tooth disease, axonal, type 2HH, 619574; Alagille syndrome 1, 118450, and a provisional association with Deafness, congenital heart defects, and posterior embryotoxon, 617992 (OMIM accessed 29th Oct 2025).
JAG1 is linked to Alagille syndrome in ClinGen, with a Definitive classification (April 2025). ; to: PMID: 41061854 Menguy et al., 2025 (in press)
Cohort of 203 families with Autosomal dominant tubulointerstitial kidney disease (ADTKD) & kidney disease cases with unknown aetiology from the 100,000 Genomes project - 1133 patients.
Variants in JAG1 were identified in three large families with unsolved ADTKD:
Family 1: c.864G>A, p.Trp288* - not in gnomAD v4.
Family 2: c.601C>T, p.Arg201Cys - MAF in gnomAD v4 = 0.000001695 (European); Revel score = 0.89.
Family 3: c.2372+3_2372+6del - not in gnomAD v4; SpliceAI score = 0.62 Splice-altering Strong. Confirmed exon skipping, abnormal transcripts constituted 44% in patient cells.
Tubulointerstitial nephropathy was confirmed by kidney histology in 2 cases from 2 families. Variants shown to segregate with disease, with the exception of individual III-3 in Family 2, who was an asymptomatic carrier. Exome sequencing was used for families 1 & 3, and a targeted NGS panel for family 2.

Further 6 cases reported from the Necker hospital in Paris: individuals with chronic kidney disease, without proteinuria, hematuria, or uropathy. 6 rare missense variants in JAG1 were identified. Also, 2 cases from the 100,000 Genomes project were identified to harbour two different rare missense variants in JAG1. No access to supplementary material to retrieve the variant details at this time.

JAG1 expression studies & ER stress analysis in Families 2 & 3 suggests that the tubulointerstitial renal disease was due to haploinsufficiency and loss of function. While mRNA levels were comparable to WT, protein levels were reduced. JAG1 is predicted to be dosage sensitive with pLI = 1.

JAG1 is associated with several autosomal dominant phenotypes in OMIM: Tetralogy of Fallot, 187500; Charcot-Marie-Tooth disease, axonal, type 2HH, 619574; Alagille syndrome 1, 118450, and a provisional association with Deafness, congenital heart defects, and posterior embryotoxon, 617992 (OMIM accessed 29th Oct 2025).
JAG1 is linked to Alagille syndrome in ClinGen, with a Definitive classification (April 2025).
Tubulointerstitial kidney disease v3.6 JAG1 Ida Ertmanska changed review comment from: PMID: 41061854 Menguy et al., 2025 (in press)
Cohort of 203 families with Autosomal dominant tubulointerstitial kidney disease (ADTKD) & kidney disease cases with unknown aetiology from the 100,000 Genomes project - 1133 patients.
Variants in JAG1 were identified in three large families with unsolved ADTKD:
Family 1: c.864G>A, p.Trp288* - not in gnomAD v4.
Family 2: c.601C>T, p.Arg201Cys - MAF in gnomAD v4 = 0.000001695 (European); Revel score = 0.89.
Family 3: c.2372+3_2372+6del - not in gnomAD v4; SpliceAI score = 0.62 Splice-altering Strong.
Tubulointerstitial nephropathy was confirmed by kidney histology in 2 cases from 2 families. Variants shown to segregate with disease, with the exception of individual III-3 in Family 2, who was an asymptomatic carrier. Exome sequencing was used for families 1 & 3, and a targeted NGS panel for family 2.

Further 6 cases reported from the Necker hospital in Paris: individuals with chronic kidney disease, without proteinuria, hematuria, or uropathy. 6 rare missense variants in JAG1 were identified. Also, 2 cases from the 100,000 Genomes project were identified to harbour two different rare missense variants in JAG1. No access to supplementary material to retrieve the variant details at this time.

JAG1 expression studies as well ER stress analysis suggests that the tubulointerstitial renal disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function.

JAG1 is associated with several autosomal dominant phenotypes in OMIM: Tetralogy of Fallot, 187500; Charcot-Marie-Tooth disease, axonal, type 2HH, 619574; Alagille syndrome 1, 118450, and a provisional association with Deafness, congenital heart defects, and posterior embryotoxon, 617992 (OMIM accessed 29th Oct 2025).
JAG1 is linked to Alagille syndrome in ClinGen, with a Definitive classification (April 2025). ; to: PMID: 41061854 Menguy et al., 2025 (in press)
Cohort of 203 families with Autosomal dominant tubulointerstitial kidney disease (ADTKD) & kidney disease cases with unknown aetiology from the 100,000 Genomes project - 1133 patients.
Variants in JAG1 were identified in three large families with unsolved ADTKD:
Family 1: c.864G>A, p.Trp288* - not in gnomAD v4.
Family 2: c.601C>T, p.Arg201Cys - MAF in gnomAD v4 = 0.000001695 (European); Revel score = 0.89.
Family 3: c.2372+3_2372+6del - not in gnomAD v4; SpliceAI score = 0.62 Splice-altering Strong.
Tubulointerstitial nephropathy was confirmed by kidney histology in 2 cases from 2 families. Variants shown to segregate with disease, with the exception of individual III-3 in Family 2, who was an asymptomatic carrier. Exome sequencing was used for families 1 & 3, and a targeted NGS panel for family 2.

Further 6 cases reported from the Necker hospital in Paris: individuals with chronic kidney disease, without proteinuria, hematuria, or uropathy. 6 rare missense variants in JAG1 were identified. Also, 2 cases from the 100,000 Genomes project were identified to harbour two different rare missense variants in JAG1. No access to supplementary material to retrieve the variant details at this time.

JAG1 expression studies & ER stress analysis suggests that the tubulointerstitial renal disease was due to haploinsufficiency and loss of function. JAG1 is predicted to be dosage sensitive with pLI = 1.

JAG1 is associated with several autosomal dominant phenotypes in OMIM: Tetralogy of Fallot, 187500; Charcot-Marie-Tooth disease, axonal, type 2HH, 619574; Alagille syndrome 1, 118450, and a provisional association with Deafness, congenital heart defects, and posterior embryotoxon, 617992 (OMIM accessed 29th Oct 2025).
JAG1 is linked to Alagille syndrome in ClinGen, with a Definitive classification (April 2025).
Tubulointerstitial kidney disease v3.6 JAG1 Ida Ertmanska changed review comment from: PMID: 41061854 Menguy et al., 2025 (in press)
Cohort of 203 families with Autosomal dominant tubulointerstitial kidney disease (ADTKD) & unsolved kidney disease cases from the 100,000 Genomes project.
Variant in JAG1 was identified in three large families with unsolved ADTKD, and additional rare variants were identified in sporadic cases.
None of the 23 adult patients affected with isolated kidney failure (and tubulointerstitial nephritis in individuals with available kidney biopsy) had overt sign of liver, bile duct, heart, eye, or skeletal defect. JAG1 expression studies as well ER stress analysis suggests that the tubulointerstitial renal disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function.; to: PMID: 41061854 Menguy et al., 2025 (in press)
Cohort of 203 families with Autosomal dominant tubulointerstitial kidney disease (ADTKD) & kidney disease cases with unknown aetiology from the 100,000 Genomes project - 1133 patients.
Variants in JAG1 were identified in three large families with unsolved ADTKD:
Family 1: c.864G>A, p.Trp288* - not in gnomAD v4.
Family 2: c.601C>T, p.Arg201Cys - MAF in gnomAD v4 = 0.000001695 (European); Revel score = 0.89.
Family 3: c.2372+3_2372+6del - not in gnomAD v4; SpliceAI score = 0.62 Splice-altering Strong.
Tubulointerstitial nephropathy was confirmed by kidney histology in 2 cases from 2 families. Variants shown to segregate with disease, with the exception of individual III-3 in Family 2, who was an asymptomatic carrier. Exome sequencing was used for families 1 & 3, and a targeted NGS panel for family 2.

Further 6 cases reported from the Necker hospital in Paris: individuals with chronic kidney disease, without proteinuria, hematuria, or uropathy. 6 rare missense variants in JAG1 were identified. Also, 2 cases from the 100,000 Genomes project were identified to harbour two different rare missense variants in JAG1. No access to supplementary material to retrieve the variant details at this time.

JAG1 expression studies as well ER stress analysis suggests that the tubulointerstitial renal disease was not due to cell toxicity of an abnormal protein, but rather to haploinsufficiency and loss of function.

JAG1 is associated with several autosomal dominant phenotypes in OMIM: Tetralogy of Fallot, 187500; Charcot-Marie-Tooth disease, axonal, type 2HH, 619574; Alagille syndrome 1, 118450, and a provisional association with Deafness, congenital heart defects, and posterior embryotoxon, 617992 (OMIM accessed 29th Oct 2025).
JAG1 is linked to Alagille syndrome in ClinGen, with a Definitive classification (April 2025).
Tubulointerstitial kidney disease v3.6 JAG1 Ida Ertmanska reviewed gene: JAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 41061854; Phenotypes: Autosomal dominant tubulointerstitial kidney disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tubulointerstitial kidney disease v3.6 JAG1 John Sayer gene: JAG1 was added
gene: JAG1 was added to Tubulointerstitial kidney disease. Sources: Expert list
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to PMID: 41061854
Phenotypes for gene: JAG1 were set to tubulointersitial kidney disease; kidney failure
Penetrance for gene: JAG1 were set to Incomplete
Mode of pathogenicity for gene: JAG1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: JAG1 was set to GREEN
Added comment: JAG1 causes Alagile syndrome but new evidence shows it can give renal limited phenotypes resembling ADTKD
Sources: Expert list