CUL5

cullin 5, the group of Cullins

Basic information

Region (hg38): 11:108008897-108107761

Links

ENSG00000166266 ∙ NCBI:8065 ∙ OMIM:601741 ∙ HGNC:2556 ∙ Uniprot:Q93034 ∙ 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 CUL5 gene.

• Inborn genetic diseases (8 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CUL5 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	1
missense			7			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	7	0	1

Variants in CUL5

This is a list of pathogenic ClinVar variants found in the CUL5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-108009361-A-C		not specified	Uncertain significance (May 23, 2023)
11-108033848-C-T		not specified	Uncertain significance (Nov 17, 2023)
11-108046348-G-T		not specified	Uncertain significance (Sep 15, 2021)
11-108046360-A-G			Benign (Jun 29, 2020)
11-108054933-G-A		not specified	Uncertain significance (Apr 25, 2022)
11-108054947-G-A		not specified	Uncertain significance (Mar 14, 2023)
11-108072364-G-C		not specified	Uncertain significance (Jul 26, 2022)
11-108078223-A-T		not specified	Uncertain significance (Apr 28, 2023)
11-108088527-G-A		not specified	Likely benign (Jul 12, 2023)
11-108094847-G-T		not specified	Uncertain significance (Mar 25, 2022)
11-108097703-A-G		not specified	Uncertain significance (Feb 01, 2023)
11-108098419-G-A		not specified	Uncertain significance (Oct 02, 2023)
11-108098480-G-A		not specified	Uncertain significance (Dec 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CUL5	protein_coding	protein_coding	ENST00000393094	19	99045

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000300	125644	0	6	125650	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.59	136	392	0.347	0.0000196	5180
Missense in Polyphen		21	152.16	0.13801		2048
Synonymous	-0.914	147	134	1.10	0.00000682	1338
Loss of Function	6.07	3	48.8	0.0615	0.00000288	597

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000386	0.0000386
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000593	0.0000544
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.0000182	0.0000176
Middle Eastern	0.0000593	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin- conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. Seems to be involved in proteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Apoptosis-related network due to altered Notch3 in ovarian cancer;Dual hijack model of Vif in HIV infection;Disease;Signal Transduction;Host Interactions of HIV factors;HIV Infection;Post-translational protein modification;Metabolism of proteins;Infectious disease;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Downregulation of ERBB2 signaling;Neddylation;Vif-mediated degradation of APOBEC3G;Signaling by ERBB2;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.260

Intolerance Scores

• loftool: 0.286
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.249
• hipred: Y
• hipred_score: 0.673
• ghis: 0.684

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cul5
• Phenotype: immune 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;ubiquitin-dependent protein catabolic process;cell cycle arrest;cell population proliferation;negative regulation of cell population proliferation;viral process;protein ubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;ERBB2 signaling pathway;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;calcium ion transmembrane transport;intrinsic apoptotic signaling pathway
• Cellular component: cytosol;SCF ubiquitin ligase complex;cullin-RING ubiquitin ligase complex;Cul5-RING ubiquitin ligase complex
• Molecular function: ubiquitin-protein transferase activity;calcium channel activity;protein binding;ubiquitin protein ligase binding;signaling receptor activity;ubiquitin protein ligase activity