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Primary immunodeficiency

Gene: FADD

Green List (high evidence)

FADD (Fas associated via death domain)
EnsemblGeneIds (GRCh38): ENSG00000168040
EnsemblGeneIds (GRCh37): ENSG00000168040
OMIM: 602457, Gene2Phenotype
FADD is in 4 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, 12:46 p.m. | Last Modified: 14 Oct 2020, 12:46 p.m.
Panel Version: 2.248
The following PubMed IDs were added to gene FADD (OMIM gene MIM#602457): 18070632;25794656;21109225. 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)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
functional hyposplenism; invasive pneumococcal disease; para-infectious encephalopathy and hepatopathy; cardiovascular malformations

Publications

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
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): FADD .PanelApp HGNC gene symbol check: FADD . IUIS Disease: FADD deficiency . IUIS Inheritance: AR .T cells: Normal numbers, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Functional hyposplenism, bacterial and viral infections, recurrent episodes of encephalopathy and liver dysfunction. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Autoimmune Lymphoproliferative Syndrome (ALPS, Canale Smith syndrome)
Created: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed Amber to Green from external review comment and further publications to support gene-disease association
Created: 20 Jun 2018, 10:22 p.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.
Created: 20 Jun 2018, 10:20 p.m.
Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Created: 20 Jun 2018, 10:19 p.m.
Keep Amber until more info on gene and disease association, refer to external expert review
Created: 18 Jun 2018, 1:30 p.m.
Characterized by severe bacterial and viral infections, congenital heart defects and recurrent episodes of fever, liver
dysfunction, and seizures.
Created: 18 Jun 2018, 1:22 p.m.
Comment on publications: FADD-related immunodeficiency is a rare genetic immunological disease reported in a single consanguineous Pakistani family with several affected members presenting with severe bacterial and viral infections, recurrent hepatopathy (portal inflammation, fibrosis), and recurrent, stereotypical febrile episodes, sometimes lasting several days, with encephalopathy and difficult-to-control seizure. Bolze et al. (2010) PMID: 21109225 reported 2 sisters and their cousin from a large consanguineous Pakistani pedigree with recurrent infections associated with encephalopathy, hepatic dysfunction, and cardiovascular malformations caused by a 315T-G transversion in exon 2. The mutation segregated with disease in the family and was not found in 282 Pakistani controls. Bolze et al. (2010) concluded that the C105W mutation strongly decreases steady-state protein levels and impairs the interaction of the residual FADD protein with FAS. Analysis of FAS-induced apoptosis in patients' cells confirmed that the C105W mutant impairs apoptotic function both in vitro and in vivo.
Created: 18 Jun 2018, 1:10 p.m.
Comment on mode of inheritance: added MOI
Created: 18 Jun 2018, 1:05 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: FADD, PanelApp HGNC gene symbol check: FADD, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Autoimmune lymphoproliferative syndrome (ALPS) / ALPS-like disease
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: FADD, GRID_Gene_Symbol: FADD, GRID_Transcript_ENS_Community submitted: ENST00000301838, GRID_Transcript_RefSeq: NM_003824.3, GRID_Transcript_ENS_used_on_Production: ENST00000301838
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
  • Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations, 613759
  • ALPS-like disease
  • functional hyposplenism
  • invasive pneumococcal disease
  • para-infectious encephalopathy and hepatopathy
  • cardiovascular malformations
  • Functional hyposplenism, bacterial and viral infections, recurrent episodes of encephalopathy and liver dysfunction
  • Diseases of Immune Dysregulation
OMIM
602457
Clinvar variants
Variants in FADD
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: fadd 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 FADD. Publications for gene FADD were updated from 21109225; 17656375; 25794656 to 18070632; 17656375; 25794656; 21109225 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 FADD.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to FADD.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to FADD.

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 FADD were set to Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations, 613759, ALPS-like disease, functional hyposplenism, invasive pneumococcal disease, para-infectious encephalopathy and hepatopathy, cardiovascular malformations, Functional hyposplenism, bacterial and viral infections, recurrent episodes of encephalopathy and liver dysfunction, Diseases of Immune Dysregulation

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

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

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

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

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

20 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: FADD were set to Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations, 613759; ALPS-like disease; functional hyposplenism; invasive pneumococcal disease; para-infectious encephalopathy and hepatopathy; cardiovascular malformations

20 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: FADD were set to 21109225; 17656375; 25794656

18 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: FADD were set to Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations, 613759; ALPS-like disease

18 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: FADD were set to 21109225; 17656375

18 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: FADD were set to 21109225

18 Jun 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: FADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to FADD. 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 FADD. Panel: Primary immunodeficiency disorders Phenotypes for gene FADD were set to Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations, ALPS-like disease

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene FADD were set to Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

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

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

FADD was created by Louise Daugherty