COP1
protein-codingCOP1 E3 ubiquitin ligase, the group of Cilia and flagella associated|WD repeat domain containing|Ring finger proteins|Small nucleolar RNA protein coding host genes
Gene summary
Enables ubiquitin protein ligase activity. Involved in several processes, including negative regulation of fatty acid biosynthetic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and response to ionizing radiation. Part of Cul4A-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jun 2026]
- RFWD2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~262.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to COP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022457.7. 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 | 2 | 1 | 3 | |||
| missense | 80 | 1 | 2 | 83 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 89 | 3 | 3 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071902.2 | 20 | MANE Select | |
| Ensembl | ENSP00000356641.3 | 20 | MANE Select | |
| RefSeq | NP_001001740.1 | 19 | Standard | |
| RefSeq | NP_001273573.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p53 signaling pathway - Homo sapiens (human)
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Post-translational protein modification
- Metabolism of proteins
- Autodegradation of the E3 ubiquitin ligase COP1
Biological Process
- response to ionizing radiation
- protein ubiquitination
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process
- proteasome-mediated ubiquitin-dependent protein catabolic process
- post-translational protein modification
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- Golgi membrane
- nucleoplasm
- cytosol
- nuclear speck
- Cul4A-RING E3 ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367669
- Coding exons
- 20
- Length
- 262663
- Individuals with no LoFs
- 125708
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125719
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.53 | 222 | 356 | 0.623 | 0.0000171 | 4799 |
| Missense (PolyPhen) | 25 | 110.84 | 0.22554 | 1456 | ||
| Synonymous | -0.110 | 131 | 129 | 1.01 | 0.00000614 | 1344 |
| Loss of Function | 5.69 | 4 | 45.4 | 0.0881 | 0.00000265 | 520 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000073 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation. Upon binding to TRIB1, ubiquitinates CEBPA, which lacks a canonical COP1-binding motif (Probable). {ECO:0000269|PubMed:12466024, ECO:0000269|PubMed:12615916, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15103385, ECO:0000269|PubMed:19805145, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:21625211, ECO:0000303|PubMed:27041596}.;
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.58
Essentials
- Essential (gene trap)
- N