UBE2L3
protein-codingubiquitin conjugating enzyme E2 L3, the group of Ubiquitin conjugating enzymes E2
Gene summary
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is demonstrated to participate in the ubiquitination of p53, c-Fos, and the NF-kB precursor p105 in vitro. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007915
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UBE2L3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003347.4. 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 | 1 | 2 | |||
| missense | 5 | 5 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 9 | 0 | 1 | 10 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003338.1 | 4 | MANE Select | |
| Ensembl | ENSP00000344259.5 | 4 | MANE Select | |
| RefSeq | NP_001243284.1 | 4 | Standard | |
| RefSeq | NP_001243285.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Parkinson,s disease - Homo sapiens (human)
- Parkin-Ubiquitin Proteasomal System pathway
- Parkinsons Disease Pathway
- role of parkin in ubiquitin-proteasomal pathway
Biological Process
- protein polyubiquitination
- regulation of transcription, DNA-templated
- cellular protein modification process
- ubiquitin-dependent protein catabolic process
- cell population proliferation
Molecular Function
- transcription coactivator activity
- RNA binding
- ubiquitin-protein transferase activity
- protein binding
- ATP binding
Cellular Component
- ubiquitin ligase complex
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000458578
- Coding exons
- 4
- Length
- 74588
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.88 | 9 | 82.6 | 0.109 | 0.00000471 | 1382 |
| Missense (PolyPhen) | 1 | 29.266 | 0.03417 | 423 | ||
| Synonymous | 1.35 | 21 | 30.5 | 0.688 | 0.00000184 | 429 |
| Loss of Function | 2.27 | 0 | 6.00 | 0.00 | 2.52e-7 | 103 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN and ARIH1, that function like function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down- regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis. {ECO:0000269|PubMed:10888878, ECO:0000269|PubMed:15367689, ECO:0000269|PubMed:17003263, ECO:0000269|PubMed:18946090, ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:21532592}.;
Recessive Scores
- pRec
- 0.268
Intolerance Scores
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 63.81
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |