UBE2V1
protein-codingubiquitin conjugating enzyme E2 V1, the group of Ubiquitin conjugating enzymes E2
Gene summary
Ubiquitin-conjugating E2 enzyme variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein encoded by this gene is located in the nucleus and can cause transcriptional activation of the human FOS proto-oncogene. It is thought to be involved in the control of differentiation by altering cell cycle behavior. Alternatively spliced transcript variants encoding multiple isoforms have been described for this gene, and multiple pseudogenes of this gene have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (Kua-UEV), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Apr 2012]
- UBE2V
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.8 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 UBE2V1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001032288.3. 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 | 1 | 1 | ||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 0 | 1 | 1 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001027459.1 | 4 | MANE Select | |
| Ensembl | ENSP00000360739.4 | 4 | MANE Select | |
| RefSeq | NP_001244322.1 | 4 | Standard | |
| RefSeq | NP_001244323.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- IL-1 signaling pathway
- Interleukin-1 Induced Activation of NF-kappa-B
- Simplified Depiction of MYD88 Distinct Input-Output Pathway
- TLR NFkB
- Toll Like Receptor 7/8 (TLR7/8) Cascade
Biological Process
- activation of MAPK activity
- protein polyubiquitination
- regulation of DNA repair
- postreplication repair
- regulation of transcription, DNA-templated
Molecular Function
- protein binding
- ubiquitin conjugating enzyme activity
Cellular Component
- ubiquitin ligase complex
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340309
- Coding exons
- 4
- Length
- 34836
- Individuals with no LoFs
- 125684
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125697
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.55 | 50 | 91.7 | 0.545 | 0.00000465 | 1104 |
| Missense (PolyPhen) | 5 | 16.578 | 0.30161 | 230 | ||
| Synonymous | -0.642 | 35 | 30.5 | 1.15 | 0.00000156 | 313 |
| Loss of Function | 0.769 | 7 | 9.57 | 0.732 | 5.75e-7 | 106 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000059 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000064 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has no ubiquitin ligase activity on its own. The UBE2V1- UBE2N heterodimer catalyzes the synthesis of non-canonical poly- ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. {ECO:0000269|PubMed:11057907, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:9305758, ECO:0000269|PubMed:9418904, ECO:0000269|PubMed:9580084, ECO:0000269|PubMed:9705497}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.914
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.11
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |