CUL5
protein-codingcullin 5, the group of Cullins
Gene summary
Enables ubiquitin ligase complex scaffold activity and ubiquitin protein ligase binding activity. Involved in several processes, including negative regulation of cell-substrate junction organization; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein K11-linked ubiquitination. Located in site of DNA damage. Part of Cul5-RING ubiquitin ligase complex. Is active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~98.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CUL5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003478.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 37 | 37 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 42 | 1 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003469.2 | 19 | MANE Select | |
| Ensembl | ENSP00000376808.2 | 19 | MANE Select | |
| Ensembl | ENSP00000435376.1 | 19 | Standard | |
| Ensembl | ENSP00000436494.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
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
Molecular Function
- ubiquitin-protein transferase activity
- calcium channel activity
- protein binding
- ubiquitin protein ligase binding
- signaling receptor activity
Cellular Component
- cytosol
- SCF ubiquitin ligase complex
- cullin-RING ubiquitin ligase complex
- Cul5-RING ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393094
- Coding exons
- 19
- Length
- 99045
- Individuals with no LoFs
- 125644
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125650
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.59 | 136 | 392 | 0.347 | 0.0000196 | 5180 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000039 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000059 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.260
Intolerance Scores
- LoFtool
- 0.286
- RVIS EVS
- -0.74
- RVIS percentile EVS
- 13.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.896
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |