COPS3

COP9 signalosome subunit 3, the group of COP9 signalosome

Basic information

Region (hg38): 17:17246616-17281273

Links

ENSG00000141030

∙ NCBI:8533 ∙ OMIM:604665 ∙ HGNC:2239 ∙ Uniprot:Q9UNS2 ∙ 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 COPS3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COPS3 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				1 clinvar	1 clinvar	2
missense			10 clinvar			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1 clinvar		1
Total	0	0	10	2	1

Variants in COPS3

This is a list of pathogenic ClinVar variants found in the COPS3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
17-17248951-G-C	not specified	Uncertain significance (Feb 05, 2024)	3076271
17-17249012-T-C	not specified	Uncertain significance (Jan 22, 2024)	3076270
17-17249049-G-A		Likely benign (Feb 27, 2018)	780065
17-17254898-C-G	not specified	Uncertain significance (Nov 18, 2023)	3076274
17-17262045-A-G	not specified	Uncertain significance (Aug 19, 2023)	2596995
17-17270967-G-A	not specified	Uncertain significance (Jul 18, 2024)	2346768
17-17270985-C-G	not specified	Uncertain significance (Dec 14, 2022)	2216354
17-17270985-C-T	not specified	Uncertain significance (Oct 27, 2023)	3076273
17-17270991-A-T	not specified	Uncertain significance (Aug 15, 2023)	2618894
17-17276048-C-T	not specified	Uncertain significance (Jan 29, 2024)	3076272
17-17276130-C-G	not specified	Uncertain significance (Nov 09, 2024)	3495993
17-17281136-A-G		Likely benign (Aug 01, 2022)	2647519
17-17281181-C-T		Benign (Jan 03, 2018)	708422

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COPS3	protein_coding	protein_coding	ENST00000268717	12	34467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000508	125742	0	1	125743	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	129	230	0.561	0.0000114	2803
Missense in Polyphen		18	60.894	0.29559		773
Synonymous	0.174	84	86.1	0.976	0.00000465	764
Loss of Function	4.57	1	26.2	0.0381	0.00000135	307

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
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: 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. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, 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:9535219}.;
Pathway: DNA Repair;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Clathrin-mediated endocytosis;Neddylation;Cargo recognition for clathrin-mediated endocytosis;TNFalpha;DNA Damage Recognition in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Formation of TC-NER Pre-Incision Complex;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

pRec: 0.121

Intolerance Scores

loftool: 0.155
rvis_EVS: -0.54
rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

pHI: 0.484
hipred: Y
hipred_score: 0.859
ghis: 0.652

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.784

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Cops3
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); embryo phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: protein deneddylation;nucleotide-excision repair, DNA damage recognition;in utero embryonic development;transcription-coupled nucleotide-excision repair;ubiquitin-dependent protein catabolic process;signal transduction;response to light stimulus;post-translational protein modification
Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;COP9 signalosome
Molecular function: protein binding