Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: COPA

Green List (high evidence)

PMID: 38175705 reports on 6 cases from 3 families with heterozygous mutations in the C-terminal domain of COPA underlying a complex autoinflammatory syndrome.

Created: 18 Oct 2024, 9:59 a.m. | Last Modified: 18 Oct 2024, 9:59 a.m.

Panel Version: 6.16

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
a complex autoinflammatory syndrome

Publications

• PMID: 38175705

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, 12:39 p.m. | Last Modified: 14 Oct 2020, 12:39 p.m.

Panel Version: 2.239

The following PubMed IDs were added to entity COPA: 25894502. These publications have been associated with OMIM phenotype MIM#616414, which is listed for this entity, by the autoinflammation 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

• 25894502

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

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

Green List (high evidence)

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): COPA .PanelApp HGNC gene symbol check: COPA . IUIS Disease: COPA defect . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: PMN and tissue specific cells. IUIS Associated features: Autoimmune inflammatory arthritis and interstitial lung disease with Th17 dysregulation and autoantibody production. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Non-Inflammasome Related Conditions

Created: 2 Jul 2018, 10:35 a.m.

Comment on list classification: changed rating from Amber to Green, there is enough evidence to support the role of COPA in immune dysfunction

Created: 4 Jun 2018, 1:20 p.m.

added Jensson et al. (2017) PMID:29137621 describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. This is the second report of the p.Glu241Lys mutation in COPA, indicating the recurrent nature of the mutation. The mutation was reported to co-segregate with COPA syndrome in a large family from the USA with five affected members, and classified as pathogenic. The two separate occurrences of the p.Glu241Lys mutation in cases and its absence from a large number of sequenced genomes confirms its role in the pathogenesis of the COPA syndrome.

Created: 4 Jun 2018, 1:18 p.m.

Comment on publications: added Noorelahi et al. (2018) PMID: 28956095 describe a 12-year-old boy presenting with dyspnea on exertion, fatigue and clubbing. Additional findings included a restrictive pattern of pulmonary involvement and positive inflammatory markers and autoantibodies. Genetic testing revealed a p.W240R variant of the COPA gene confirming the diagnosis of Copa syndrome.

Created: 4 Jun 2018, 1:08 p.m.

added missense-tag. Currently only missense variants have been reported

Created: 4 Jun 2018, 1:02 p.m.

Comment on publications: added publications to support COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis.

Created: 4 Jun 2018, 12:59 p.m.

from Watkin et al. (2015) i PMID: 25894502 In 30 individuals from 5 unrelated families with Autoimmune interstitial lung, joint, and kidney disease identified 4 different heterozygous missense mutations in the COPA gene (601924.0001-601924.0004). All mutations affected the WD40 domain. Nine mutation carriers were clinically unaffected, consistent with incomplete penetrance. It has been indicated that the variants contribute to susceptibility susceptibility to infection.

Created: 4 Jun 2018, 12:46 p.m.

COPA syndrome is an autoinflammatory disease that presents as pulmonary hemosiderosis and polyarticular arthritis. COPA gene encodes a subunit of the coatomer protein complex (COPI), a carrier complex required for retrograde protein trafficking from the Golgi to the endoplasmic reticulum (ER)

Created: 4 Jun 2018, 11:24 a.m.

Comment on phenotypes: added MIMid from OMIM and phenotype from Orphanet

Created: 4 Jun 2018, 11:21 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 supplied by GRID. GRID Gene Symbol HGNC PanelApp check: COPA, GRID_Gene_Symbol: COPA, GRID_Transcript_ENS_Community submitted: ENST00000368069, GRID_Transcript_RefSeq: NM_001098398.1, GRID_Transcript_ENS_used_on_Production: ENST00000368069

Created: 17 Apr 2018, 12:12 p.m.