CUL2

cullin 2, the group of Cullins|MicroRNA protein coding host genes

Basic information

Region (hg38): 10:35008503-35127006

Links

ENSG00000108094 ∙ NCBI:8453 ∙ OMIM:603135 ∙ HGNC:2552 ∙ Uniprot:Q13617 ∙ 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 CUL2 gene.

• Inborn genetic diseases (21 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CUL2 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	2
missense			20	1		21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding			1			1
Total	0	0	21	1	2

Variants in CUL2

This is a list of pathogenic ClinVar variants found in the CUL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-35010318-A-G		not specified	Uncertain significance (Jun 29, 2023)
10-35010333-T-C		not specified	Uncertain significance (May 11, 2022)
10-35010339-G-A		not specified	Uncertain significance (Nov 27, 2023)
10-35010357-A-G		Moyamoya angiopathy	Likely pathogenic (-)
10-35010427-T-C		not specified	Uncertain significance (Apr 12, 2022)
10-35011943-C-A		not specified	Uncertain significance (Apr 25, 2023)
10-35016247-G-A		not specified	Uncertain significance (Jan 26, 2022)
10-35016285-C-A		not specified	Uncertain significance (Feb 10, 2022)
10-35028849-C-T			Benign (Apr 10, 2018)
10-35028862-G-A		not specified	Uncertain significance (Feb 10, 2022)
10-35031364-T-C		not specified	Uncertain significance (May 24, 2023)
10-35031582-G-A		not specified	Uncertain significance (Jul 19, 2022)
10-35035188-T-C		not specified	Uncertain significance (Jul 25, 2023)
10-35035215-T-C		not specified	Uncertain significance (May 05, 2023)
10-35035225-T-C		not specified	Uncertain significance (Aug 01, 2022)
10-35035261-A-T		not specified	Uncertain significance (Jan 08, 2024)
10-35038937-C-T		not specified	Uncertain significance (Dec 03, 2021)
10-35039045-C-T		not specified	Uncertain significance (Mar 31, 2023)
10-35044646-G-T		not specified	Uncertain significance (May 17, 2023)
10-35044652-G-A		not specified	Uncertain significance (Apr 25, 2023)
10-35044661-A-C		not specified	Uncertain significance (Dec 06, 2023)
10-35044860-C-A		not specified	Uncertain significance (Aug 10, 2023)
10-35049676-C-G			Benign (Apr 10, 2018)
10-35049707-C-T		not specified	Uncertain significance (Aug 12, 2021)
10-35049745-C-T			Benign (May 08, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CUL2	protein_coding	protein_coding	ENST00000537177	21	82092

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.81e-8	125688	0	6	125694	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.25	217	400	0.542	0.0000211	5091
Missense in Polyphen		42	122.83	0.34194		1704
Synonymous	0.799	123	135	0.912	0.00000747	1283
Loss of Function	6.49	1	51.0	0.0196	0.00000296	608

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000914	0.0000909
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000367	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). May serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF). {ECO:0000269|PubMed:10973499, ECO:0000269|PubMed:11384984, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:9122164}.
• Pathway: Renal cell carcinoma - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Type 2 papillary renal cell carcinoma;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of Hypoxia-inducible Factor (HIF) by oxygen;Cellular response to hypoxia;Cellular responses to stress;Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Cellular responses to external stimuli;Neddylation (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.59

Haploinsufficiency Scores

• pHI: 0.724
• hipred: Y
• hipred_score: 0.739
• ghis: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.833

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cul2

Zebrafish Information Network

• Gene name: cul2
• Affected structure: intersegmental vessel
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;ubiquitin-dependent protein catabolic process;cell cycle arrest;negative regulation of cell population proliferation;viral process;protein ubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;regulation of transcription from RNA polymerase II promoter in response to hypoxia;intrinsic apoptotic signaling pathway
• Cellular component: nucleoplasm;nucleolus;cytosol;SCF ubiquitin ligase complex;VCB complex;cullin-RING ubiquitin ligase complex;Cul2-RING ubiquitin ligase complex
• Molecular function: protein binding;ubiquitin protein ligase binding;protein-containing complex binding;ubiquitin protein ligase activity