UBE2O
protein-codingubiquitin conjugating enzyme E2 O
Gene summary
Enables ubiquitin conjugating enzyme activity and ubiquitin protein ligase activity. Involved in positive regulation of BMP signaling pathway; protein ubiquitination; and retrograde transport, endosome to Golgi. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~63.7 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 UBE2O variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022066.4. 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 | 2 | 1 | 4 | ||
| missense | 135 | 2 | 137 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 140 | 4 | 1 | 145 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071349.3 | 18 | MANE Select | |
| Ensembl | ENSP00000323687.6 | 18 | MANE Select | |
| Ensembl | ENSP00000468498.1 | 10 | Standard | |
| Ensembl | ENSP00000467623.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- protein ubiquitylation
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
Biological Process
- protein monoubiquitination
- positive regulation of BMP signaling pathway
- retrograde transport, endosome to Golgi
- protein K63-linked ubiquitination
Molecular Function
- RNA binding
- ubiquitin-protein transferase activity
- protein binding
- ATP binding
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000319380
- Coding exons
- 18
- Length
- 63757
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.44 | 482 | 747 | 0.645 | 0.0000466 | 8439 |
| Missense (PolyPhen) | 149 | 302.77 | 0.49212 | 3296 | ||
| Synonymous | 0.597 | 304 | 318 | 0.957 | 0.0000223 | 2576 |
| Loss of Function | 6.51 | 3 | 55.3 | 0.0543 | 0.00000301 | 627 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| 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) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin- associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). {ECO:0000269|PubMed:23381138, ECO:0000269|PubMed:23452853, ECO:0000269|PubMed:23455153, ECO:0000269|PubMed:24703950}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.163
- RVIS EVS
- -0.81
- RVIS percentile EVS
- 12.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.871
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |