COPB1
protein-codingCOPI coat complex subunit beta 1, the group of Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing|COPI coat complex
Gene summary
This gene encodes a protein subunit of the coatomer complex associated with non-clathrin coated vesicles. The coatomer complex, also known as the coat protein complex 1, forms in the cytoplasm and is recruited to the Golgi by activated guanosine triphosphatases. Once at the Golgi membrane, the coatomer complex may assist in the movement of protein and lipid components back to the endoplasmic reticulum. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2009]
- COPB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~56.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0031002
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0031002
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: Allergy/Immunology/Infectious
Rationale: Among other features, individuals have been described with immunodeficiency, and awareness may allow preventive measures and early and aggressive treatment of infections
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to COPB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001144061.2. 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 | 1 | 14 | 15 | |||
| missense | 2 | 94 | 1 | 97 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 10 | 12 | |||
| Total | 2 | 2 | 107 | 15 | 0 | 126 |
Highest pathogenic variant AF is 0.00092306617
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001137533.1 | 21 | MANE Select | |
| Ensembl | ENSP00000397873.2 | 21 | MANE Select | |
| RefSeq | NP_001137534.1 | 21 | Standard | |
| RefSeq | NP_057535.1 | 21 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| copb1 | Danio rerio | Structure: muscle cell Quality: structure abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Vesicle-mediated transport
- Membrane Trafficking
- Glycosphingolipid biosynthesis - neolactoseries
- Post-translational protein modification
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
- viral process
Molecular Function
- structural molecule activity
- protein binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum membrane
- endoplasmic reticulum-Golgi intermediate compartment
- Golgi apparatus
- Golgi-associated vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000249923
- Coding exons
- 21
- Length
- 56588
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125737
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.38 | 354 | 505 | 0.702 | 0.0000255 | 6276 |
| Missense (PolyPhen) | 127 | 225.84 | 0.56234 | 2785 | ||
| Synonymous | 0.764 | 162 | 175 | 0.927 | 0.00000883 | 1810 |
| Loss of Function | 5.85 | 5 | 49.4 | 0.101 | 0.00000279 | 614 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| 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. Plays a functional role in facilitating the transport of kappa- type opioid receptor mRNAs into axons and enhances translation of these proteins. Required for limiting lipid storage in lipid droplets. Involved in lipid homeostasis by regulating the presence of perilipin family members PLIN2 and PLIN3 at the lipid droplet surface and promoting the association of adipocyte surface triglyceride lipase (PNPLA2) with the lipid droplet to mediate lipolysis (By similarity). Involved in the Golgi disassembly and reassembly processes during cell cycle. Involved in autophagy by playing a role in early endosome function. Plays a role in organellar compartmentalization of secretory compartments including endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), Golgi, trans-Golgi network (TGN) and recycling endosomes, and in biosynthetic transport of CAV1. Promotes degradation of Nef cellular targets CD4 and MHC class I antigens by facilitating their trafficking to degradative compartments. {ECO:0000250, ECO:0000269|PubMed:18385291, ECO:0000269|PubMed:18725938, ECO:0000269|PubMed:19364919, ECO:0000269|PubMed:20056612}.;
Recessive Scores
- pRec
- 0.258
Intolerance Scores
- LoFtool
- 0.0571
- RVIS EVS
- -1.11
- RVIS percentile EVS
- 6.72
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.756
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |