Autoinflammatory disorders

Gene: COPA

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 2:17 p.m. | Last Modified: 10 Dec 2025, 2:17 p.m.

Panel Version: 2.34

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autoimmune interstitial lung, joint, and kidney disease

Publications

• PMID: 27048656
• PMID: 31455335
• PMID: 3976718
• PMID: 34900872
• PMID: 30385646
• Jensson, B.O., Hansdottir, S., Arnadottir, G.A. et al. COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA . BMC Med Genet 18, 129 (2017).

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Created: 8 May 2025, 11 a.m. | Last Modified: 8 May 2025, 11 a.m.

Panel Version: 2.5

Heterozygous variants in the COPA gene cause an autoinflammatory disorder that affects multiple organ systems. Affected individuals usually present in the first decade of life with variable features including interstitial lung disease with or without pulmonary hemorrhage, inflammatory arthritis, recurrent infections, and renal disease. Laboratory studies show evidence of systemic inflammation.

At least 9 unrelated families with more than 20 affected individuals have been reported in the literature (PMIDs: PMID: 25894502; 31455335; 38175705).

Variant hotspots include the WD40 domain and the C-terminal domain of the COPA protein.
Sources: Literature

Created: 8 May 2025, 11 a.m.

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

Phenotypes
{Autoinflammation and autoimmunity, systemic, with immune dysregulation}, OMIM:616414; COPA syndrome

Publications

• 25894502
• 31455335
• 38175705