PEDS1-UBE2V1
protein-codingPEDS1-UBE2V1 readthrough
Gene summary
The TMEM189-UEV mRNA is an infrequent but naturally occurring read-through transcript of the neighboring TMEM189 and UBE2V1 genes. 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 produced by this transcript has UEV1 B domains but the protein is localized to the cytoplasm rather than to the nucleus. The significance of this read-through mRNA and the function of its protein product has not yet been determined. [provided by RefSeq, Oct 2010]
- TMEM189-UBE2V1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~72.5 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 PEDS1-UBE2V1 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 1 | 0 | 1 | 2 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_954673.2 | 8 | Standard | |
| Ensembl | ENSP00000344166.2 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in squamous cell - TarBase
- TLR NFkB
- Toll Like Receptor 7/8 (TLR7/8) Cascade
Biological Process
- postreplication repair
- protein K63-linked ubiquitination
Molecular Function
- ubiquitin conjugating enzyme activity
Cellular Component
- nucleus
- nucleoplasm
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000341698
- Coding exons
- 8
- Length
- 72514
- Individuals with no LoFs
- 125665
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125673
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.43 | 112 | 211 | 0.530 | 0.0000124 | 2374 |
| Missense (PolyPhen) | 27 | 66.263 | 0.40747 | 630 | ||
| Synonymous | -1.18 | 95 | 81.4 | 1.17 | 0.00000490 | 713 |
| Loss of Function | 2.65 | 7 | 19.7 | 0.356 | 0.00000110 | 203 |
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 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000088 | rare |
| South Asian | 0.000098 | 0.000098 | 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}.;
Intolerance Scores
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.31
Essentials
- Essential (CRISPR)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0718
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |