COPA Gene - Coatomer Subunit Alpha
COPA gene encodes the alpha subunit of the coatomer protein complex I (COPI), involved in intracellular vesicle transport and associated with autoimmune and inflammatory disorders.
Gene Information Card
| Symbol | COPA |
|---|---|
| Full Name | Coatomer Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.2 |
| NCBI Gene ID | 1314 ncbi.nlm.nih.gov/gene/1314 |
| Ensembl ID | ENSG00000122218 |
| UniProt ID | P53621 |
| OMIM ID | 601924 |
| HGNC ID | 2230 |
| Aliases | HEP-COP, alpha-COP, COPI, ARCN1, HEPCOP |
Description
The COPA gene encodes the alpha subunit of the coatomer protein complex I (COPI). This complex is essential for retrograde vesicular transport from the Golgi apparatus to the endoplasmic reticulum (ER). COPA mutations disrupt protein trafficking, leading to ER stress and immune dysregulation, and are associated with an autosomal dominant autoimmune disorder known as COPA syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| COPA syndrome (autoimmune interstitial lung, joint, and kidney disease) | Missense mutations in the WD40 domain impair COPI function, causing ER stress and activation of the unfolded protein response (UPR), leading to autoinflammation and autoimmunity. | ClinVar, OMIM #616414 |
| Autoimmune hemolytic anemia | Dysregulated immune response secondary to COPA mutation; reported in COPA syndrome patients. | ClinVar, PubMed |
| Pulmonary alveolar proteinosis (secondary) | Impaired surfactant clearance due to altered vesicle trafficking in alveolar macrophages. | PubMed, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 28.5 | High |
| Kidney | 22.3 | High |
| Liver | 18.7 | Medium |
| Brain | 15.2 | Medium |
| Heart | 14.8 | Medium |
| Skeletal Muscle | 12.1 | Medium |
| Pancreas | 10.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 32.1 | High expression |
| HEK293 (embryonic kidney) | 25.4 | High expression |
| HepG2 (hepatocellular carcinoma) | 20.8 | Medium expression |
| K562 (leukemia) | 14.3 | Medium expression |
| SH-SY5Y (neuroblastoma) | 11.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.698G>A (p.Arg233His) | Missense | ~30% of COPA syndrome cases | Disrupts WD40 domain, dominant negative effect |
| c.700C>T (p.Arg234Cys) | Missense | ~15% | Impaired COPI assembly, ER stress |
| c.712G>A (p.Glu238Lys) | Missense | ~10% | Altered cargo binding, UPR activation |
| c.721A>G (p.Asn241Asp) | Missense | ~5% | Reduced retrograde transport, immune dysregulation |
Mutation functional classification
Loss of Function (LOF)
Not typically observed; complete loss is likely embryonic lethal.
Gain of Function (GOF)
Not reported; mutations are not activating.
Dominant Negative (DN)
Yes. Missense mutations in the WD40 domain produce a defective alpha-COP subunit that interferes with wild-type COPI function, leading to ER stress and autoimmunity.
View complete mutation data：
Gene Ontology (GO)
| • structural molecule activity (GO:0005198) | • intracellular protein transport (GO:0006886) |
| • retrograde vesicle-mediated transport, Golgi to ER (GO:0006890) | • vesicle-mediated transport (GO:0016192) |
| • COPI vesicle coat (GO:0030126) | • protein N-terminus binding (GO:0047485) |
Pathways
• COPI-dependent Golgi-to-ER retrograde transport (Reactome R-HSA-6811434)
• Vesicle-mediated transport (Reactome R-HSA-5653656)
• ER stress and unfolded protein response (Reactome R-HSA-381119)
Protein Summary
The COPA protein (alpha-COP) is a 1224-amino-acid subunit of the heptameric COPI coatomer complex. It contains an N-terminal WD40 domain that mediates protein-protein interactions and cargo recognition. Alpha-COP is essential for maintaining Golgi architecture and retrograde transport. Mutations in the WD40 domain cause COPA syndrome, an autosomal dominant disorder characterized by interstitial lung disease, arthritis, and renal involvement due to ER stress and aberrant immune activation.
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