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Primary immunodeficiency

Gene: PSMA3

Amber List (moderate evidence)

PSMA3 (proteasome subunit alpha 3)
EnsemblGeneIds (GRCh38): ENSG00000100567
EnsemblGeneIds (GRCh37): ENSG00000100567
OMIM: 176843, Gene2Phenotype
PSMA3 is in 2 panels

5 reviews

Abdelazeem Elhabyan (Arizona State University)

I don't know

it is involved in dysregulation of the immune response leading to a vicious cycle of uncontrolled inflammation in both hematopoietic and nonhematopoietic cells which is thought to be the cause of complications in COVID-19 patients.


Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production
PMID: 26524591
he defects were associated with induction of a type I interferon response with strong expression of IFN-inducible genes and an increase in chemokines and cytokines. Brehm et al. (2015) concluded that mutations in proteasomal subunit genes adversely affect proteasomal function, leading to cell stress and the triggering of a type I IFN gene response, causing a vicious cycle of uncontrolled inflammation in both hematopoietic and nonhematopoietic cells.
Created: 10 Apr 2020, 1:30 p.m. | Last Modified: 10 Apr 2020, 1:30 p.m.
Panel Version: 2.51

Kimberly Gilmour (Great Ormond Street Hopsital)

I don't know

agree with all the Amber genes
Created: 25 Sep 2019, 1:49 p.m. | Last Modified: 25 Sep 2019, 1:49 p.m.
Panel Version: 1.115

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

I think CANDLE should be green
Created: 26 Sep 2019, 12:43 p.m. | Last Modified: 26 Sep 2019, 12:43 p.m.
Panel Version: 1.127
The amber genes are covered on our targeted exome, we feel that these should be covered in the testing
Created: 25 Sep 2019, 1:44 p.m. | Last Modified: 25 Sep 2019, 1:44 p.m.
Panel Version: 1.114

Sophie Hambleton (Newcastle University)

Red List (low evidence)

Not described as associated with a stand-alone disorder (though variants may modulate disease severity in CANDLE/PRAAS patients)
Created: 29 Jun 2018, 3:08 p.m.

Louise Daugherty (Genomics England Curator)

I don't know

Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber.
Created: 12 Nov 2019, 5:03 p.m. | Last Modified: 12 Nov 2019, 5:03 p.m.
Panel Version: 1.137
?Proteasome-associated autoinflammatory syndrome 1, digenic. Two unrelated children het
for this and another gene (PSMB8) hence ?digenic - amber on association
Created: 26 Sep 2019, 3:58 p.m. | Last Modified: 26 Sep 2019, 3:58 p.m.
Panel Version: 1.130
Comment on list classification: Changed rating from Red to Amber to reflect the agreed rating agreed by the GMS Immunology Specialist Test Group, but flagged for further follow up with the Immunology Test Group due to the subsequent conflicting review. Evidence /opinion needs consensus before upgrading to Green
Created: 25 Sep 2019, 3:12 p.m. | Last Modified: 26 Sep 2019, 1:03 p.m.
Panel Version: 1.127
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. Although discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 to rate Amber in the confirmed follow up email on 20th June North West GLH reasserted that PSMA3 should be Green
Created: 25 Sep 2019, 3 p.m. | Last Modified: 26 Sep 2019, 11:17 a.m.
Panel Version: 1.126
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 only enough evidence to rate this gene Amber
Created: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.
Panel Version: 1.116
Comment on publications: PMID:26524591 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. Flagged for further discussion with the Specialist Test Group as conflicts with the Amber rating agreed in the webex 28th March 2019
Created: 15 Aug 2019, 4:20 p.m. | Last Modified: 12 Sep 2019, 3:32 p.m.
Panel Version: 1.55
Comment on list classification: External expert review notes Red status due to no evident link to immunodeficiency, rather variants are modulators rather than a direct gene-disease association, so I have kept this gene Red on this panel until further evidence. Referred back to Victorian Clinical Genetics Services for evidences.
Created: 4 Jul 2018, 5:59 p.m.
Comment on list classification: 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 from Victorian Clinical Genetics Services. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1. No disorder or MOI was listed in the submitted list.
Created: 26 Jun 2018, 12:45 p.m.

Details

Sources
  • Expert Review Amber
  • North West GLH
  • London North GLH
  • NHS GMS
  • Victorian Clinical Genetics Services
Phenotypes
  • CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)
OMIM
176843
Clinvar variants
Variants in PSMA3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

25 Sep 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psma3 has been classified as Amber List (Moderate Evidence).

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to PSMA3.

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to PSMA3.

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to PSMA3.

15 Aug 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PSMA3 were changed from to CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)

15 Aug 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PSMA3 were set to

12 Jul 2018, Gel status: 1

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.

4 Jul 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psma3 has been classified as Red List (Low Evidence).

4 Jul 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psma3 has been classified as Red List (Low Evidence).

26 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psma3 has been classified as Amber List (Moderate Evidence).

26 Jun 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

PSMA3 was added to Primary immunodeficiency disorders panel. Sources: Victorian Clinical Genetics Services

26 Jun 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

PSMA3 was created by Louise Daugherty