COPS4
protein-codingCOP9 signalosome subunit 4, the group of COP9 signalosome
Gene summary
This gene encodes one of eight subunits composing COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~41.4 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 COPS4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016129.3. 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 | 1 | ||||
| missense | 21 | 21 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 29 | 0 | 0 | 29 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057213.2 | 10 | MANE Select | |
| Ensembl | ENSP00000264389.2 | 10 | MANE Select | |
| RefSeq | NP_001244935.1 | 9 | Standard | |
| RefSeq | NP_001317656.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA Repair
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- protein deneddylation
- nucleotide-excision repair, DNA damage recognition
- transcription-coupled nucleotide-excision repair
- post-translational protein modification
Molecular Function
- protein binding
- NEDD8-specific protease activity
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- synaptic vesicle
- COP9 signalosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264389
- Coding exons
- 10
- Length
- 41372
- Individuals with no LoFs
- 124865
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124866
- p
- 0.00000400
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.14 | 88 | 218 | 0.403 | 0.0000113 | 2663 |
| Missense (PolyPhen) | 11 | 65.172 | 0.16878 | 772 | ||
| Synonymous | -1.21 | 90 | 76.5 | 1.18 | 0.00000389 | 740 |
| Loss of Function | 4.36 | 1 | 24.1 | 0.0415 | 0.00000118 | 294 |
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 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:21102408, ECO:0000269|PubMed:9535219}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.0530
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.25
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |