UBE2H
protein-codingubiquitin conjugating enzyme E2 H, 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. The encoded protein sequence is 100% identical to the mouse homolog and 98% identical to the frog and zebrafish homologs. Three alternatively spliced transcript variants have been found for this gene and they encode distinct isoforms. [provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~122.2 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 UBE2H variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003344.4. 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 | 2 | 2 | ||||
| missense | 1 | 4 | 5 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 0 | 6 | 2 | 0 | 9 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003335.1 | 7 | MANE Select | |
| Ensembl | ENSP00000347836.3 | 7 | MANE Select | |
| RefSeq | NP_001189427.1 | 4 | Standard | |
| RefSeq | NP_874356.1 | 5 | 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
- ubiquitin-dependent protein catabolic process
- protein ubiquitination
- proteasome-mediated ubiquitin-dependent protein catabolic process
- protein K48-linked ubiquitination
- protein K11-linked ubiquitination
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- ATP binding
- ubiquitin conjugating enzyme activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355621
- Coding exons
- 7
- Length
- 122218
- Individuals with no LoFs
- 125456
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125457
- p
- 0.00000399
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.30 | 10 | 105 | 0.0951 | 0.00000545 | 1203 |
| Missense (PolyPhen) | 0 | 35.305 | 0 | 453 | ||
| Synonymous | 0.686 | 36 | 41.6 | 0.865 | 0.00000266 | 325 |
| Loss of Function | 3.13 | 1 | 13.3 | 0.0749 | 7.43e-7 | 148 |
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) | 0.0000088 | 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 (PubMed:8132613, PubMed:17588522, PubMed:20061386). E2 ubiquitin conjugating enzyme that transfers ubiquitin to MAEA, a core component of the CTLH E3 ubiquitin-protein ligase complex (PubMed:29911972). In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination (PubMed:20061386). Capable, in vitro, to ubiquitinate histone H2A (PubMed:8132613). {ECO:0000269|PubMed:17588522, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:8132613}.;
Recessive Scores
- pRec
- 0.292
Intolerance Scores
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.974