COPS5
COP9 signalosome subunit 5, the group of JAMM/MPN+ metallopeptidase family|COP9 signalosome
Basic information
Region (hg38): 8:67043079-67083783
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the COPS5 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 6 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 6 | 0 | 0 |
Variants in COPS5
This is a list of pathogenic ClinVar variants found in the COPS5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-67045822-T-C | not specified | Uncertain significance (Nov 10, 2022) | ||
| 8-67045895-C-A | not specified | Uncertain significance (Jan 11, 2023) | ||
| 8-67051247-A-T | not specified | Uncertain significance (Dec 18, 2023) | ||
| 8-67059389-A-T | not specified | Uncertain significance (Dec 20, 2023) | ||
| 8-67061855-C-T | not specified | Uncertain significance (Oct 27, 2022) | ||
| 8-67061947-T-C | not specified | Uncertain significance (May 30, 2024) | ||
| 8-67064144-C-G | Benign (Jun 26, 2018) | |||
| 8-67064342-C-T | Likely benign (Nov 01, 2022) | |||
| 8-67064343-G-A | Likely benign (Mar 20, 2020) | |||
| 8-67064384-GCCCGGAGGTCTGTCA-G | Joubert syndrome 21 | Uncertain significance (Jul 01, 2022) | ||
| 8-67064387-C-T | not specified | Likely benign (Oct 13, 2017) | ||
| 8-67064399-A-C | not specified | Uncertain significance (Sep 20, 2018) | ||
| 8-67064399-A-T | Joubert syndrome 21 | Uncertain significance (Jun 28, 2022) | ||
| 8-67064400-T-A | Joubert syndrome 21 | Uncertain significance (Mar 10, 2022) | ||
| 8-67064400-T-G | Joubert syndrome 21 | Uncertain significance (Feb 09, 2022) | ||
| 8-67064402-C-G | Joubert syndrome 21 | Uncertain significance (Jun 04, 2022) | ||
| 8-67064403-T-A | Joubert syndrome 21 | Uncertain significance (Mar 14, 2023) | ||
| 8-67064406-T-A | Joubert syndrome 21 | Uncertain significance (Aug 01, 2023) | ||
| 8-67064407-C-A | Joubert syndrome 21 | Uncertain significance (Jul 09, 2021) | ||
| 8-67064409-C-G | Joubert syndrome 21 | Uncertain significance (Jul 26, 2022) | ||
| 8-67064410-G-C | Joubert syndrome 21 | Likely benign (Aug 10, 2023) | ||
| 8-67064411-C-A | Joubert syndrome 21 | Uncertain significance (Aug 16, 2022) | ||
| 8-67064411-C-T | Joubert syndrome 21 | Uncertain significance (Apr 22, 2022) | ||
| 8-67064421-C-T | Joubert syndrome 21 | Uncertain significance (Jul 26, 2022) | ||
| 8-67064423-G-C | Inborn genetic diseases | Uncertain significance (Mar 31, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| COPS5 | protein_coding | protein_coding | ENST00000357849 | 8 | 40705 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000752 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.44 | 50 | 180 | 0.278 | 0.00000865 | 2207 |
| Missense in Polyphen | 8 | 58.34 | 0.13713 | 736 | ||
| Synonymous | 0.960 | 56 | 65.9 | 0.850 | 0.00000340 | 600 |
| Loss of Function | 4.22 | 0 | 20.8 | 0.00 | 0.00000115 | 236 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Probable protease subunit 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 the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, 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. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:9535219}.;
- Pathway
- TGF-beta Signaling Pathway;DNA Repair;hypoxia-inducible factor in the cardivascular system;Vesicle-mediated transport;erythropoietin mediated neuroprotection through nf-kb;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Clathrin-mediated endocytosis;TGF_beta_Receptor;Neddylation;Cargo recognition for clathrin-mediated endocytosis;DNA Damage Recognition in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Formation of TC-NER Pre-Incision Complex;AP-1 transcription factor network;HIF-1-alpha transcription factor network;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair
(Consensus)
Recessive Scores
- pRec
- 0.315
Intolerance Scores
- loftool
- rvis_EVS
- -0.12
- rvis_percentile_EVS
- 44.54
Haploinsufficiency Scores
- pHI
- 0.964
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.661
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.871
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |
Mouse Genome Informatics
- Gene name
- Cops5
- Phenotype
- immune system phenotype; embryo phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- cops5
- Affected structure
- macula utricle
- Phenotype tag
- abnormal
- Phenotype quality
- has fewer parts of type
Gene ontology
- Biological process
- protein deneddylation;nucleotide-excision repair, DNA damage recognition;transcription-coupled nucleotide-excision repair;transcription by RNA polymerase II;translation;translational initiation;protein deubiquitination;negative regulation of apoptotic process;post-translational protein modification;positive regulation of transcription by RNA polymerase II;regulation of JNK cascade;positive regulation of DNA-binding transcription factor activity;regulation of cell cycle;regulation of IRE1-mediated unfolded protein response;exosomal secretion
- Cellular component
- chromatin;nucleus;nucleoplasm;cytoplasm;cytosol;eukaryotic translation initiation factor 3 complex;synaptic vesicle;COP9 signalosome;cell junction;perinuclear region of cytoplasm
- Molecular function
- transcription coactivator activity;translation initiation factor activity;metalloendopeptidase activity;thiol-dependent ubiquitin-specific protease activity;protein binding;metallopeptidase activity;NEDD8-specific protease activity;enzyme binding;macrophage migration inhibitory factor binding;metal ion binding