Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: JAK1
Comment on mode of pathogenicity: Two of monoallelic variants were shown to be gain-of-function, one is mosaic and the other is somatic. Hence, MOP is set as 'Other'. In addition, 'mosaicism' and 'somatic' tags were added.Created: 30 Oct 2023, 6:45 p.m. | Last Modified: 30 Oct 2023, 6:46 p.m.
Panel Version: 4.70
Comment on mode of inheritance: There is sufficient evidence available for the association of monoallelic variants in this gene to Autoinflammation, immune dysregulation, and eosinophilia (MIM #618999). However, the evidence for the association of biallelic variants is not sufficient for green rating. Hence, the MOI is set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.Created: 30 Oct 2023, 6:43 p.m. | Last Modified: 30 Oct 2023, 6:43 p.m.
Panel Version: 4.68
As reviewed by Hannah Knight, there are four unrelated patients with monoallelic JAK1 variants, of which one is somatic and another is mosaic. In addition, mice with Jak1 knock-in missense mutation recapitulated key aspects of the human phenotype.
In addition, there is one patient with bialleic JAK1 variant and JAK1 conditional deletion mouse model in support of this association.Created: 30 Oct 2023, 6:40 p.m. | Last Modified: 30 Oct 2023, 6:40 p.m.
Panel Version: 4.67
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autoinflammation, immune dysregulation, and eosinophilia, OMIM:618999
Publications
Mode of pathogenicity
Other
Now four families reported, and variants seem to cluster.
PMID: 28111307 - mother and two sons with immune disorder. De novo variant in mother, also in both children (p.A634D)
PMID: 32750333 - early-onset multi-organ immune dysregulation resulting from a mosaic variant not found in either parent (p.S703I)
PMID: 34496019 - somatic variant found in a patient with hypereosinophilia (p.R629_S632delinsSA)
PMID: 35046931 - novel variant (p.H596D) in an individual with a unique autoinflammatory keratinization disease
Also one report of biallelic disease in 2016 (PMID: 28008925), but none others since thenCreated: 10 Oct 2023, 11:56 a.m. | Last Modified: 10 Oct 2023, 11:57 a.m.
Panel Version: 4.35
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autoinflammation, immune dysregulation, and eosinophilia
Publications
The following PubMed IDs were added to gene JAK1 (OMIM gene MIM#147795): 28111307. These publications have been associated with the gene by the immunedysregulation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Publications
Comment on publications: added publications suggested from external expert review to support gene-disease associationCreated: 6 Jul 2018, 1:51 p.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.Created: 6 Jul 2018, 1:50 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): JAK1 .PanelApp HGNC gene symbol check: JAK1 . IUIS Disease: JAK1 . IUIS Inheritance: AD GOF .T cells: N/A, .B cells: Not assessed, .IUIS Other affected cells: N/A. IUIS Associated features: HSM, eosinophilia, eosinophilic enteritis, thyroid disease, poor growth, viral infections. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Autoimmunity with or without Lymphoproliferation. // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): JAK1 .PanelApp HGNC gene symbol check: JAK1 . IUIS Disease: JAK1 . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N + L. IUIS Associated features: Susceptibility to mycobacteria and viruses, urothelial carcinoma. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Mendelian Susceptibility to mycobacterial disease (MSMD).Created: 2 Jul 2018, 10:55 a.m.
one kindred each so far published with AR loss and AD gain of function variants, producing allelic disorders.Created: 29 Jun 2018, 9:31 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
hypereosinophilic syndrome; susceptibility to mycobacterial and viral infections
Publications
Mode of pathogenicity
Other
Gene: jak1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: JAK1 were changed from Susceptibility to mycobacteria and viruses, urothelial carcinoma; Hypereosinophilic syndrome; Defects in Intrinsic and Innate Immunity; Diseases of Immune Dysregulation; HSM, eosinophilic enteritis, thyroid disease, poor growth, viral infections; HSM, eosinophilia, eosinophilic enteritis, thyroid disease, poor growth, viral infections to Autoinflammation, immune dysregulation, and eosinophilia, OMIM:618999
Publications for gene: JAK1 were set to 32086639; 28111307; 32048120; 28008925; 30671064; 32750333; 34496019; 35046931
Publications for gene: JAK1 were set to 32086639; 28111307; 32048120
Tag mosaicism tag was added to gene: JAK1. Tag somatic tag was added to gene: JAK1.
Mode of pathogenicity for gene: JAK1 was changed from None to Other
Mode of pathogenicity for gene: JAK1 was changed from Other - please provide details in the comments to None
Mode of inheritance for gene: JAK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q4_23_promote_green tag was added to gene: JAK1. Tag Q4_23_NHS_review tag was added to gene: JAK1.
Source Other was added to JAK1. Publications for gene JAK1 were updated from 32048120; 28111307; 32086639 to 32086639; 28111307; 32048120
Source IUIS Classification December 2019 was added to JAK1. Mode of inheritance for gene JAK1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Diseases of Immune Dysregulation; HSM, eosinophilic enteritis, thyroid disease, poor growth, viral infections for gene: JAK1 Publications for gene JAK1 were updated from 28111307 to 32048120; 28111307; 32086639
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Gene: jak1 has been classified as Red List (Low Evidence).
Mode of pathogenicity for gene: JAK1 was changed to Other - please provide details in the comments
Publications for gene: JAK1 were set to 28111307
Mode of inheritance for gene: JAK1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: JAK1 were set to HSM, eosinophilia, eosinophilic enteritis, thyroid disease, poor growth, viral infections; Diseases of Immune Dysregulation; Susceptibility to mycobacteria and viruses, urothelial carcinoma; Defects in Intrinsic and Innate Immunity; Hypereosinophilic syndrome
Phenotypes for gene: JAK1 were set to HSM, eosinophilia, eosinophilic enteritis, thyroid disease, poor growth, viral infections; Diseases of Immune Dysregulation; Susceptibility to mycobacteria and viruses, urothelial carcinoma; Defects in Intrinsic and Innate Immunity
JAK1 was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018
JAK1 was created by Louise Daugherty