UBE2C
protein-codingubiquitin conjugating enzyme E2 C, 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, ubiquitin-conjugating enzymes, and ubiquitin-protein ligases. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is required for the destruction of mitotic cyclins and for cell cycle progression, and may be involved in cancer progression. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been defined on chromosomes 4, 14, 15, 18, and 19. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.4 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 UBE2C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007019.4. 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 | ||||
| missense | 16 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 22 | 0 | 0 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008950.1 | 6 | MANE Select | |
| Ensembl | ENSP00000348838.4 | 6 | MANE Select | |
| RefSeq | NP_001268670.1 | 5 | Standard | |
| RefSeq | NP_001268671.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Gastric Cancer Network 1
- Gastric Cancer Network 2
- Senescence-Associated Secretory Phenotype (SASP)
- Cellular Senescence
Biological Process
- ubiquitin-dependent protein catabolic process
- exit from mitosis
- free ubiquitin chain polymerization
- protein ubiquitination
- anaphase-promoting complex-dependent catabolic process
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- ATP binding
- ubiquitin-like protein ligase binding
- ubiquitin conjugating enzyme activity
Cellular Component
- ubiquitin ligase complex
- nucleus
- nucleoplasm
- anaphase-promoting complex
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356455
- Coding exons
- 6
- Length
- 4382
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.505 | 86 | 100 | 0.858 | 0.00000487 | 1151 |
| Missense (PolyPhen) | 13 | 25.957 | 0.50082 | 360 | ||
| Synonymous | 1.56 | 31 | 44.1 | 0.702 | 0.00000250 | 355 |
| Loss of Function | 1.88 | 3 | 9.14 | 0.328 | 3.86e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000088 | 0.000088 | 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'- and 'Lys-48'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by initiating 'Lys-11'-linked polyubiquitin chains on APC/C substrates, leading to the degradation of APC/C substrates by the proteasome and promoting mitotic exit. {ECO:0000269|PubMed:15558010, ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:19820702, ECO:0000269|PubMed:19822757, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:27259151}.;
Recessive Scores
- pRec
- 0.234
Intolerance Scores
- LoFtool
- 0.873
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |