UBE2W
protein-codingubiquitin conjugating enzyme E2 W, the group of Ubiquitin conjugating enzymes E2
Gene summary
This gene encodes a nuclear-localized ubiquitin-conjugating enzyme (E2) that, along with ubiquitin-activating (E1) and ligating (E3) enzymes, coordinates the addition of a ubiquitin moiety to existing proteins. The encoded protein promotes the ubiquitination of Fanconi anemia complementation group proteins and may be important in the repair of DNA damage. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~98.8 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 UBE2W variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018299.6. 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 | 0 | |||||
| missense | 4 | 4 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 8 | 0 | 0 | 8 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060769.5 | 6 | MANE Select | |
| Ensembl | ENSP00000473561.1 | 6 | MANE Select | |
| RefSeq | NP_001001481.3 | 7 | Standard | |
| RefSeq | NP_001257944.2 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Post-translational protein modification
- protein ubiquitylation
- Metabolism of proteins
- Synthesis of active ubiquitin: roles of E1 and E2 enzymes
Biological Process
- DNA repair
- protein monoubiquitination
- protein quality control for misfolded or incompletely synthesized proteins
- protein ubiquitination
- proteasome-mediated ubiquitin-dependent protein catabolic process
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- ATP binding
- ubiquitin protein ligase binding
- ubiquitin conjugating enzyme activity
Cellular Component
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000419880
- Coding exons
- 7
- Length
- 98814
- Individuals with no LoFs
- 117288
- Homozygous LoFs
- 179
- Heterozygous LoFs
- 7155
- Defined
- 124622
- p
- 0.0299
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.81 | 43 | 91.8 | 0.468 | 0.00000416 | 1225 |
| Missense (PolyPhen) | 7 | 31.657 | 0.22112 | 418 | ||
| Synonymous | -0.111 | 32 | 31.2 | 1.03 | 0.00000151 | 349 |
| Loss of Function | 2.33 | 4 | 13.1 | 0.305 | 7.86e-7 | 145 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0083 | 0.0082 | notable |
| Latino/Admixed American | 0.022 | 0.022 | notable |
| Ashkenazi Jewish | 0.058 | 0.058 | notable |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.029 | 0.029 | notable |
| European (Non-Finnish) | 0.046 | 0.045 | notable |
| South Asian | 0.0018 | 0.0018 | notable |
| Other | 0.035 | 0.034 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:20061386, PubMed:21229326). Specifically monoubiquitinates the N-terminus of various substrates, including ATXN3, MAPT/TAU, POLR2H/RPB8 and STUB1/CHIP, by recognizing backbone atoms of disordered N-termini (PubMed:23560854, PubMed:23696636, PubMed:25436519). Involved in degradation of misfolded chaperone substrates by mediating monoubiquitination of STUB1/CHIP, leading to recruitment of ATXN3 to monoubiquitinated STUB1/CHIP, and restriction of the length of ubiquitin chain attached to STUB1/CHIP substrates by ATXN3. After UV irradiation, but not after mitomycin-C (MMC) treatment, acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway (PubMed:19111657, PubMed:21229326). In vitro catalyzes 'Lys-11'-linked polyubiquitination. UBE2W-catalyzed ubiquitination occurs also in the presence of inactive RING/U-box type E3s, i.e. lacking the active site cysteine residues to form thioester bonds with ubiquitin, or even in the absence of E3, albeit at a slower rate (PubMed:25436519). {ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:21229326, ECO:0000269|PubMed:23560854, ECO:0000269|PubMed:23696636, ECO:0000269|PubMed:25436519}.;
Recessive Scores
- pRec
- 0.0945
Intolerance Scores
- RVIS EVS
- 0.12
- RVIS percentile EVS
- 62.38
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.443
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |