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Primary immunodeficiency

Gene: ITCH

Green List (high evidence)

ITCH (itchy E3 ubiquitin protein ligase)
EnsemblGeneIds (GRCh38): ENSG00000078747
EnsemblGeneIds (GRCh37): ENSG00000078747
OMIM: 606409, Gene2Phenotype
ITCH is in 7 panels

5 reviews

Eleanor Williams (Genomics England Curator)

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, 1:14 p.m. | Last Modified: 14 Oct 2020, 1:14 p.m.
Panel Version: 2.266
The following PubMed IDs were added to gene ITCH (OMIM gene MIM#606409): 30705142;20170897. 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

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

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
personal correspondence revealed a second, as yet unpublished, case.
Created: 2 Jul 2018, 1:53 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): ITCH .PanelApp HGNC gene symbol check: ITCH . IUIS Disease: ITCH deficiency . IUIS Inheritance: AR .T cells: Nl number, poor proliferation to antigen, .B cells: Not assessed , .IUIS Other affected cells: N/A. IUIS Associated features: Early-onset chronic lung disease (interstitial pneumonitis), autoimmunity (thyroiditis, type I diabetes, chronic diarrhea/enteropathy, and hepatitis), failure to thrive, developmental delay, dysmorphic facial features . IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Autoimmunity with or without Lymphoproliferation
Created: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed Red to Green from external expert review and further publications to support gene-disease association
Created: 27 Jun 2018, 9:50 a.m.
added founder-effect tag. Only one pathogenic variant reported in the Amish community. In view of expert review Green and functional info this gene was made Green.
Created: 27 Jun 2018, 9:48 a.m.
Loss of ITCH function has also been associated with a gastrointestinal inflammatory phenotype in both mice and humans Kathania et al. 2016 (PMID:27322655), Lohr et al., 2010 (PMID:2017089), Ramon et al., 2011 (PMID:20962770), Tao et al., 2009 (PMID:19592251)
Created: 27 Jun 2018, 9:37 a.m.
Comment on phenotypes: added phenotype from orphanet
Created: 27 Jun 2018, 9:06 a.m.
Comment on publications: added publication to support phenotype. Lohr et al. (2010) described 10 Old Order Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with facial dysmorphism sequenced the candidate gene ITCH and identified homozygosity for a 1-bp insertion (394insA) in exon 6, resulting in a frameshift predicted to truncate ITCH at residue 139. Variant: NM_031483.6(ITCH): c.394dupA (p.Ile132Asnfs).
Created: 27 Jun 2018, 9:06 a.m.
Comment on phenotypes: added phenotype from orphanet
Created: 27 Jun 2018, 9:06 a.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: ITCH, PanelApp HGNC gene symbol check: ITCH, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) / Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: ITCH, GRID_Gene_Symbol: ITCH, GRID_Transcript_ENS_Community submitted: ENST00000374864, GRID_Transcript_RefSeq: NM_031483.4, GRID_Transcript_ENS_used_on_Production: ENST00000374864
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Autoimmune disease, multisystem, with facial dysmorphism, 613385
  • Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
  • Syndromic multisystem autoimmune disease due to Itch deficiency
  • Early-onset chronic lung disease (interstitial pneumonitis), autoimmunity (thyroiditis, type I diabetes, chronic diarrhea/enteropathy, and hepatitis), failure to thrive, developmental delay, dysmorphic facial features
  • Diseases of Immune Dysregulation
Tags
founder-effect
OMIM
606409
Clinvar variants
Variants in ITCH
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Oct 2020, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: itch has been classified as Green List (High Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications, Status Update

Eleanor Williams (Genomics England Curator)

Source Other was added to ITCH. Publications for gene ITCH were updated from 20170897; 26854353; 19592251; 20962770; 27322655 to 30705142; 20962770; 26854353; 20170897; 19592251; 27322655 Rating Changed from Green List (high evidence) to Red List (low evidence)

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to ITCH.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to ITCH.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to ITCH.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism, 613385, Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), Syndromic multisystem autoimmune disease due to Itch deficiency, Early-onset chronic lung disease (interstitial pneumonitis), autoimmunity (thyroiditis, type I diabetes, chronic diarrhea/enteropathy, and hepatitis), failure to thrive, developmental delay, dysmorphic facial features, Diseases of Immune Dysregulation

27 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: itch has been classified as Green List (High Evidence).

27 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: itch has been classified as Green List (High Evidence).

27 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ITCH were set to 20170897; 26854353; 19592251; 20962770; 27322655

27 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism, 613385; Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED); Syndromic multisystem autoimmune disease due to Itch deficiency

27 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ITCH were set to 20170897

27 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism, 613385; Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED); Syndromic multisystem autoimmune disease due to Itch deficiency

27 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ITCH were set to 20170897

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to ITCH. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to ITCH. Panel: Primary immunodeficiency disorders

21 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism, 613385; Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to ITCH. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to ITCH. Panel: Primary immunodeficiency disorders Phenotypes for gene ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism, Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

ITCH was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

ITCH was created by Louise Daugherty