COPA
protein-codingCOPI coat complex subunit alpha, the group of WD repeat domain containing|Receptor ligands|COPI coat complex
Gene summary
In eukaryotic cells, protein transport between the endoplasmic reticulum and Golgi compartments is mediated in part by non-clathrin-coated vesicular coat proteins (COPs). Seven coat proteins have been identified, and they represent subunits of a complex known as coatomer. The subunits are designated alpha-COP, beta-COP, beta-prime-COP, gamma-COP, delta-COP, epsilon-COP, and zeta-COP. The alpha-COP, encoded by COPA, shares high sequence similarity with RET1P, the alpha subunit of the coatomer complex in yeast. Also, the N-terminal 25 amino acids of alpha-COP encode the bioactive peptide, xenin, which stimulates exocrine pancreatic secretion and may act as a gastrointestinal hormone. Alternative splicing results in multiple splice forms encoding distinct isoforms. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014629
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014629
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to COPA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004371.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 15 | 214 | 12 | 241 | ||
| missense | 4 | 4 | 396 | 92 | 7 | 503 |
| nonsense | 1 | 6 | 7 | |||
| start loss | 0 | |||||
| frameshift | 5 | 5 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 5 | 4 | 433 | 306 | 19 | 767 |
Highest pathogenic variant AF is 6.223395e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004362.2 | 33 | MANE Select | |
| Ensembl | ENSP00000241704.7 | 33 | MANE Select | |
| RefSeq | NP_001091868.1 | 33 | Standard | |
| Ensembl | ENSP00000357048.3 | 33 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| copa | Danio rerio | Structure: muscle cell Quality: structure abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Glycosphingolipid biosynthesis - neolactoseries
- Post-translational protein modification
- Metabolism of proteins
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
Molecular Function
- hormone activity
- structural molecule activity
Cellular Component
- Golgi membrane
- extracellular space
- cytoplasm
- endoplasmic reticulum membrane
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368069
- Coding exons
- 33
- Length
- 54128
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.56 | 441 | 707 | 0.624 | 0.0000395 | 8082 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000067 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000095 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.184
Intolerance Scores
- LoFtool
- 0.312
- RVIS EVS
- -0.98
- RVIS percentile EVS
- 8.85
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.687
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |