Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: IKBKBThe mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 2 Feb 2023, 11:32 a.m. | Last Modified: 2 Feb 2023, 11:32 a.m.
Panel Version: 3.4
Comment on mode of inheritance: Should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update. Both inheritance patterns are associated with a relevant phenotype of primary immunodeficiency, but AR disease is more severe with earlier onset.Created: 13 Jun 2022, 11:02 a.m. | Last Modified: 13 Jun 2022, 11:02 a.m.
Panel Version: 2.554
Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 14 Oct 2020, 12:58 p.m. | Last Modified: 14 Oct 2020, 12:58 p.m.
Panel Version: 2.255
The following PubMed IDs were added to gene IKBKB (OMIM gene MIM#603258): 24369075;25216719. These publications have been associated with the gene by the immunodeficiencies 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
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Please note this recent publication reporting two patients from unrelated families with the same de novo heterozygous gain-of-function missense mutation. Mouse model recapitulated phenotype. Would suggest that both mono-allelic and bi-allelic variants should be assessed for pathogenicity.Created: 25 Oct 2018, 7:47 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
combined immune deficiency
Publications
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Added publication referenced by IUIS december 2019 updateCreated: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): IKBKB .PanelApp HGNC gene symbol check: IKBKB . IUIS Disease: IKBKB deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Nl number, poor function, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent bacterial, viral, fungal infections, opportunistic infections. IUIS Major category: Immunodeficiencies affecting cellular and humoral immunity. IUIS Subcategory: Combined Immunodeficiencies Generally Less Profound than Severe Combined ImmunodeficiencyCreated: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed Amber to Green from external review and further publications to support gene-disease associationCreated: 21 Jun 2018, 12:51 p.m.
Comment on publications: added publication to support gene-disease associationCreated: 21 Jun 2018, 12:50 p.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: IKBKB, PanelApp HGNC gene symbol check: IKBKB, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / Combined immunodeficiency (CID) / Combined immunodeficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: IKBKB, GRID_Gene_Symbol: IKBKB, GRID_Transcript_ENS_Community submitted: ENST00000520810, GRID_Transcript_RefSeq: NM_001556.2, GRID_Transcript_ENS_used_on_Production: ENST00000520810Created: 17 Apr 2018, 12:12 p.m.
Publications
Tag Q3_22_MOI was removed from gene: IKBKB.
Mode of inheritance for gene IKBKB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Tag Q3_22_MOI tag was added to gene: IKBKB.
Mode of inheritance for gene: IKBKB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IKBKB were changed from Immunodeficiency 15, 615592; Combined immunodeficiency; Recurrent bacterial, viral, fungal infections, opportunistic infections; Immunodeficiencies affecting cellular and humoral immunity to Immunodeficiency 15A, OMIM:618204 (AD); Immunodeficiency 15B, OMIM:615592 (AR); Combined immunodeficiency; Recurrent bacterial, viral, fungal infections, opportunistic infections; Immunodeficiencies affecting cellular and humoral immunity
Gene: ikbkb has been classified as Green List (High Evidence).
Source Other was added to IKBKB. Publications for gene IKBKB were updated from 25216719; 24369075; 30337470 to 30337470; 25216719; 24369075 Rating Changed from Green List (high evidence) to Red List (low evidence)
Publications for gene IKBKB were updated from 24369075; 25216719 to 25216719; 24369075; 30337470
Source NHS GMS was added to IKBKB.
Source North West GLH was added to IKBKB.
Source London North GLH was added to IKBKB.
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.
Phenotypes for gene IKBKB were set to Immunodeficiency 15, 615592, Combined immunodeficiency, Recurrent bacterial, viral, fungal infections, opportunistic infections, Immunodeficiencies affecting cellular and humoral immunity
IUIS Classification February 2018 was added to IKBKB. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to IKBKB. Panel: Primary immunodeficiency disorders
Gene: ikbkb has been classified as Green List (High Evidence).
Gene: ikbkb has been classified as Green List (High Evidence).
Publications for gene: IKBKB were set to 24369075; 25216719
Phenotypes for gene: IKBKB were set to Immunodeficiency 15, 615592; Combined immunodeficiency
Expert Review Amber was added to IKBKB. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to IKBKB. Panel: Primary immunodeficiency disorders Phenotypes for gene IKBKB were set to Immunodeficiency 15, Combined immunodeficiency
Phenotypes for gene IKBKB were set to Immunodeficiency 15
IKBKB was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
IKBKB was created by Louise Daugherty