UBE2D3
protein-codingubiquitin conjugating enzyme E2 D3, 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, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme functions in the ubiquitination of the tumor-suppressor protein p53, which is induced by an E3 ubiquitin-protein ligase. [provided by RefSeq, Jan 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.5 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 UBE2D3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181891.3. 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 | 5 | 5 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 13 | 0 | 0 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_871620.1 | 7 | MANE Select | |
| Ensembl | ENSP00000396901.2 | 7 | MANE Select | |
| RefSeq | NP_001287724.1 | 6 | Standard | |
| RefSeq | NP_003331.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Proteasome Degradation
- Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
- Regulation of Hypoxia-inducible Factor (HIF) by oxygen
Biological Process
- negative regulation of transcription by RNA polymerase II
- protein polyubiquitination
- DNA repair
- cellular protein modification process
- 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
- ubiquitin ligase complex
- nucleoplasm
- cytosol
- plasma membrane
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000357194
- Coding exons
- 7
- Length
- 74514
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125745
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.99 | 6 | 82.6 | 0.0727 | 0.00000415 | 971 |
| Missense (PolyPhen) | 0 | 23.119 | 0 | 340 | ||
| Synonymous | -0.497 | 31 | 27.7 | 1.12 | 0.00000142 | 278 |
| Loss of Function | 2.25 | 2 | 9.46 | 0.211 | 4.03e-7 | 117 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.0000090 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys- 11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA- linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML- NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:11743028, ECO:0000269|PubMed:12646252, ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:15496420, ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:18284575, ECO:0000269|PubMed:18508924, ECO:0000269|PubMed:18515077, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:21532592}.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.502
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.960
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |