Genes in panel
STRs in panel
Prev Next

Primary immunodeficiency

Gene: PSMB9

Amber List (moderate evidence)

PSMB9 (proteasome subunit beta 9)
EnsemblGeneIds (GRCh38): ENSG00000240065
EnsemblGeneIds (GRCh37): ENSG00000240065
OMIM: 177045, Gene2Phenotype
PSMB9 is in 2 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

PMID: 33727065 (2021) - a de novo PSMB9 p.G156D variant identified in a 1-month old boy who developed fever, a chilblain-like skin rash, myositis, and severe pulmonary hypertension due to the hyperactivation of IFN-α. In vitro experiments using patient-derived primary cells and cell lines transduced with the mutant gene revealed reduced proteasome activities. The patient responded to treatment with a Janus kinase inhibitor, tofacitinib, and later received stem cell transplantation - following which he no longer required tofacitinib and experienced no disease recurrence.
Created: 27 Sep 2021, 3:56 p.m. | Last Modified: 27 Sep 2021, 3:56 p.m.
Panel Version: 2.470

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

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)

I don't know

Variants may contribute to CANDLE syndrome but not reported as a stand-alone disorder
Created: 29 Jun 2018, 3:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Autoinflammation, lipodystrophy, and dermatosis syndrome

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, 5:04 p.m. | Last Modified: 12 Nov 2019, 5:04 p.m.
Panel Version: 1.137
?Proteasome-associated autoinflammatory syndrome 3, digenic. One patient, one similar patient het for this and another gene (PSMB4) 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: 26 Sep 2019, 10:54 a.m. | Last Modified: 26 Sep 2019, 1:06 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 PSMB9 should be Green
Created: 25 Sep 2019, 3 p.m. | Last Modified: 26 Sep 2019, 1:06 p.m.
Panel Version: 1.127
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. Added digenic tag - from review comment 'Digenic also reported'.
Created: 15 Aug 2019, 4:25 p.m. | Last Modified: 12 Sep 2019, 3:35 p.m.
Panel Version: 1.55
added digenic tag - from review comment 'Digenic also reported' from NWGLH (Tracy Briggs)
Created: 15 Aug 2019, 4:13 p.m. | Last Modified: 15 Aug 2019, 4:13 p.m.
Panel Version: 1.43
Comment on list classification: Changed from Amber to Red until more info to support gene-disease association. Expert review notes that is it currently it is thought variants contribute to CANDLE syndrome but not reported as a stand-alone disorder. Gene not present on any other PID related panels or within ESID or IUIS classifications. Request evidences / immunological association of this gene from Victorian Clinical Genetics Services.
Created: 5 Jul 2018, 10:15 a.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

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • North West GLH
  • London North GLH
  • NHS GMS
  • Victorian Clinical Genetics Services
Phenotypes
  • Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591
  • CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)
Tags
digenic
OMIM
177045
Clinvar variants
Variants in PSMB9
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 Sep 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: PSMB9 were set to 26524591

27 Sep 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: PSMB9 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) to Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)

26 Sep 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psmb9 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 PSMB9.

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to PSMB9.

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to PSMB9.

15 Aug 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PSMB9 were changed from CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) to Autoinflammation, lipodystrophy, and dermatosis syndrome; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)

15 Aug 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: PSMB9 were set to

15 Aug 2019, Gel status: 1

Added Tag

Louise Daugherty (Genomics England Curator)

Tag digenic tag was added to gene: PSMB9.

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.

5 Jul 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psmb9 has been classified as Red List (Low Evidence).

5 Jul 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psmb9 has been classified as Red List (Low Evidence).

5 Jul 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: PSMB9 was changed from to BIALLELIC, autosomal or pseudoautosomal

5 Jul 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PSMB9 were set to CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)

26 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psmb9 has been classified as Amber List (Moderate Evidence).

26 Jun 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

PSMB9 was added to Primary immunodeficiency disorders panel. Sources: Victorian Clinical Genetics Services

26 Jun 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

PSMB9 was created by Louise Daugherty