COP1

COP1 E3 ubiquitin ligase, the group of Cilia and flagella associated|WD repeat domain containing|Ring finger proteins|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 1:175944831-176207286

Previous symbols: [ "RFWD2" ]

Links

ENSG00000143207 ∙ NCBI:64326 ∙ OMIM:608067 ∙ HGNC:17440 ∙ Uniprot:Q8NHY2 ∙ 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 COP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COP1 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				2	1	3
missense			31	1	2	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding						0
Total	0	0	31	3	3

Variants in COP1

This is a list of pathogenic ClinVar variants found in the COP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-175947233-T-G		not specified	Uncertain significance (Dec 06, 2022)
1-175986967-C-T			Likely benign (Jul 31, 2018)
1-175987033-A-T		not specified	Uncertain significance (Mar 08, 2024)
1-175988297-T-C		not specified	Uncertain significance (Nov 17, 2022)
1-175988308-T-C		not specified	Uncertain significance (May 31, 2022)
1-175989434-A-C		not specified	Uncertain significance (May 27, 2022)
1-175989442-T-C			Benign (Apr 13, 2018)
1-176043256-C-T			Likely benign (Feb 25, 2018)
1-176043721-T-C		not specified	Uncertain significance (Dec 06, 2024)
1-176043757-C-T		not specified	Uncertain significance (Nov 06, 2023)
1-176046304-C-T		not specified	Uncertain significance (Sep 27, 2021)
1-176046311-G-A		not specified	Uncertain significance (Sep 08, 2024)
1-176081173-T-C		not specified	Uncertain significance (Jul 12, 2022)
1-176081266-T-C		not specified	Uncertain significance (Nov 09, 2024)
1-176081278-C-T		not specified	Uncertain significance (Mar 17, 2023)
1-176081294-G-A			Likely benign (Feb 13, 2018)
1-176081294-GAAA-G			Benign (Aug 14, 2017)
1-176081295-A-G			Likely benign (Apr 13, 2018)
1-176085778-G-A		not specified	Uncertain significance (May 11, 2022)
1-176085856-G-A		not specified	Uncertain significance (Aug 20, 2024)
1-176085865-C-T		not specified	Uncertain significance (Nov 24, 2024)
1-176085887-T-C		not specified	Uncertain significance (Oct 22, 2021)
1-176116654-G-T		not specified	Uncertain significance (Jun 29, 2023)
1-176116667-G-T		not specified	Uncertain significance (Nov 12, 2021)
1-176135065-G-A		not specified	Uncertain significance (Nov 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COP1	protein_coding	protein_coding	ENST00000367669	20	262663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000556	125708	0	11	125719	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.53	222	356	0.623	0.0000171	4799
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000930	0.0000924
European (Non-Finnish)	0.0000734	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;Stabilization of p53;p53-Dependent G1 DNA Damage Response;p53-Dependent G1/S DNA damage checkpoint;G1/S DNA Damage Checkpoints;Cell Cycle Checkpoints;Neddylation;Direct p53 effectors;Cell Cycle;ATM pathway (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.582
• hipred: Y
• hipred_score: 0.749
• ghis: 0.640

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Cop1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system 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); pigmentation phenotype; neoplasm; homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• 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
• Cellular component: Golgi membrane;nucleoplasm;cytosol;nuclear speck;Cul4A-RING E3 ubiquitin ligase complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;metal ion binding;ubiquitin protein ligase activity