COPA

COPI coat complex subunit alpha, the group of WD repeat domain containing|Receptor ligands|COPI coat complex

Basic information

Region (hg38): 1:160288594-160343566

Links

ENSG00000122218 ∙ NCBI:1314 ∙ OMIM:601924 ∙ HGNC:2230 ∙ Uniprot:P53621 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoimmune interstitial lung disease-arthritis syndrome (Strong), mode of inheritance: AD
• autoimmune interstitial lung disease-arthritis syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammation and autoimmunity, systemic, with immune dysregulation	AD	Allergy/Immunology/Infectious	Individuals may manifest with multisystemic autoimmune conditions, as well as recurrent infections, and medical management has been described such that early awareness may allow prompt treatment	Allergy/Immunology/Infectious	25894502; 38175705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COPA gene.

• not provided (2 variants)
• Autoimmune interstitial lung disease-arthritis syndrome (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COPA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	146	15	167
missense	3	4	252	46	10	315
nonsense			2			2
start loss						0
frameshift			2			2
inframe indel			7			7
splice donor/acceptor (+/-2bp)			3			3
splice region			27	42	5	74
non coding	1		17	133	20	171
Total	4	4	289	325	45

Variants in COPA

This is a list of pathogenic ClinVar variants found in the COPA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-160290161-C-T		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Dec 05, 2024)
1-160290168-G-A		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Mar 01, 2023)
1-160290169-C-T		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Mar 16, 2019)
1-160290176-CTG-C		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Aug 17, 2024)
1-160290179-A-G		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Aug 23, 2022)
1-160290180-T-C		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Jan 03, 2024)
1-160290182-C-T		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Oct 17, 2022)
1-160290224-A-G		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Feb 19, 2024)
1-160290224-AAAAC-A		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Apr 15, 2023)
1-160290236-G-A		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Sep 11, 2023)
1-160290236-G-C		Autoimmune interstitial lung disease-arthritis syndrome	Benign (Oct 30, 2024)
1-160290443-T-C		not specified	Benign (Nov 12, 2023)
1-160290481-AC-GA		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Dec 20, 2022)
1-160290483-A-G		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Mar 01, 2024)
1-160290492-T-C		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Jul 27, 2023)
1-160290497-T-C			Uncertain significance (Sep 18, 2024)
1-160290508-A-G			Uncertain significance (Dec 06, 2023)
1-160290511-T-C		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Jun 16, 2024)
1-160290542-C-A		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Feb 02, 2024)
1-160290548-G-A		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Nov 19, 2024)
1-160290549-T-G		Autoimmune interstitial lung disease-arthritis syndrome	Likely benign (Mar 01, 2024)
1-160290555-C-A		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Sep 01, 2021)
1-160290566-G-C		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Dec 25, 2023)
1-160290574-C-T		Autoimmune interstitial lung disease-arthritis syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 06, 2024)
1-160290575-G-A		Autoimmune interstitial lung disease-arthritis syndrome	Uncertain significance (Apr 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COPA	protein_coding	protein_coding	ENST00000368069	33	54128

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.48e-10	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.56	441	707	0.624	0.0000395	8082
Missense in Polyphen		63	165.65	0.38031		1804
Synonymous	2.55	197	248	0.794	0.0000122	2395
Loss of Function	7.64	3	73.9	0.0406	0.00000404	822

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000129	0.000129
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000949	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non- clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}.
• Disease: DISEASE: Autoimmune interstitial lung, joint, and kidney disease (AILJK) [MIM:616414]: An autoimmune disease characterized by inflammatory arthritis, interstitial lung disease, and immune complex-mediated renal disease. {ECO:0000269|PubMed:25894502}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Glycosphingolipid biosynthesis - neolactoseries;Post-translational protein modification;Metabolism of proteins;Tyrosine metabolism;Proteoglycan biosynthesis;Androgen and estrogen biosynthesis and metabolism;Glycosphingolipid biosynthesis - ganglioseries;Glycosphingolipid biosynthesis - globoseries;Purine metabolism;Pyrimidine metabolism;adp-ribosylation factor;Glycosphingolipid metabolism;Phosphatidylinositol phosphate metabolism;Prostaglandin formation from arachidonate;Methionine and cysteine metabolism;Aminosugars metabolism;Galactose metabolism;O-Glycan biosynthesis;C21-steroid hormone biosynthesis and metabolism;Glycerophospholipid metabolism;Vitamin B9 (folate) metabolism;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Arf1 pathway;COPI-dependent Golgi-to-ER retrograde traffic;C-MYB transcription factor network;Golgi-to-ER retrograde transport;COPI-mediated anterograde transport;N-Glycan biosynthesis;ER to Golgi Anterograde Transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.184

Intolerance Scores

• loftool: 0.312
• rvis_EVS: -0.98
• rvis_percentile_EVS: 8.85

Haploinsufficiency Scores

• pHI: 0.129
• hipred: Y
• hipred_score: 0.689
• ghis: 0.630

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.687

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Copa

Zebrafish Information Network

• Gene name: copa
• Affected structure: muscle cell
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: intracellular protein transport;endoplasmic reticulum to Golgi vesicle-mediated transport;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;intra-Golgi vesicle-mediated transport;regulation of signaling receptor activity;pancreatic juice secretion
• Cellular component: Golgi membrane;extracellular space;cytoplasm;endoplasmic reticulum membrane;cytosol;membrane;COPI vesicle coat;transport vesicle;extracellular exosome
• Molecular function: hormone activity;structural molecule activity