COPS5

COP9 signalosome subunit 5, the group of JAMM/MPN+ metallopeptidase family|COP9 signalosome

Basic information

Region (hg38): 8:67043078-67083783

Links

ENSG00000121022 ∙ NCBI:10987 ∙ OMIM:604850 ∙ HGNC:2240 ∙ Uniprot:Q92905 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COPS5 gene.

• Inborn genetic diseases (4 variants)

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			4			4
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	4	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 (Apr 27, 2022)
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)
8-67064424-C-A		Joubert syndrome 21	Uncertain significance (Jun 27, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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