UHRF2
protein-codingubiquitin like with PHD and ring finger domains 2, the group of Tudor domain containing|PHD finger proteins|Ring finger proteins
Gene summary
This gene encodes a nuclear protein which is involved in cell-cycle regulation. The encoded protein is a ubiquitin-ligase capable of ubiquinating PCNP (PEST-containing nuclear protein), and together they may play a role in tumorigenesis. The encoded protein contains an NIRF_N domain, a PHD finger, a set- and ring-associated (SRA) domain, and a RING finger domain and several of these domains have been shown to be essential for the regulation of cell proliferation. This protein may also have a role in intranuclear degradation of polyglutamine aggregates. Alternative splicing results in multiple transcript variants some of which are non-protein coding. [provided by RefSeq, Feb 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~93.9 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 UHRF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152896.3. 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 | 2 | 1 | 3 | |||
| missense | 61 | 3 | 64 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 66 | 4 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_690856.1 | 16 | MANE Select | |
| Ensembl | ENSP00000276893.5 | 16 | MANE Select | |
| Ensembl | ENSP00000370778.3 | 3 | Standard | |
| Ensembl | ENSP00000370778.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell cycle
- cell population proliferation
- maintenance of DNA methylation
- protein ubiquitination
- protein sumoylation
Molecular Function
- DNA binding
- ubiquitin-protein transferase activity
- protein binding
- SUMO transferase activity
- histone binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear heterochromatin
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000276893
- Coding exons
- 16
- Length
- 93904
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125747
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.32 | 244 | 440 | 0.554 | 0.0000227 | 5235 |
| Missense (PolyPhen) | 90 | 262.04 | 0.34345 | 3121 | ||
| Synonymous | -2.44 | 187 | 149 | 1.25 | 0.00000739 | 1532 |
| Loss of Function | 5.37 | 5 | 43.0 | 0.116 | 0.00000233 | 529 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| 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: E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131. {ECO:0000269|PubMed:12176013, ECO:0000269|PubMed:14741369, ECO:0000269|PubMed:15178429, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:23404503}.;
- Disease
- DISEASE: Note=Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.0576
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- 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 |