UHRF1
protein-codingubiquitin like with PHD and ring finger domains 1, the group of MicroRNA protein coding host genes|Ring finger proteins|PHD finger proteins|Tudor domain containing
Gene summary
This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to specific DNA sequences, and recruits a histone deacetylase to regulate gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition by regulating topoisomerase IIalpha and retinoblastoma gene expression, and functions in the p53-dependent DNA damage checkpoint. It is regarded as a hub protein for the integration of epigenetic information. This gene is up-regulated in various cancers, and it is therefore considered to be a therapeutic target. Multiple transcript variants encoding different isoforms have been found for this gene. A related pseudogene exists on chromosome 12. [provided by RefSeq, Feb 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0000133
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0021190
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0021190
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UHRF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001048201.3. 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 | 6 | 1 | 7 | |||
| missense | 60 | 3 | 63 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 68 | 4 | 0 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001041666.1 | 16 | MANE Select | |
| Ensembl | ENSP00000498698.1 | 16 | MANE Select | |
| RefSeq | NP_001276979.1 | 16 | Standard | |
| RefSeq | NP_001276980.1 | 16 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| uhrf1 | Danio rerio | Structure: intestinal epithelial cell Quality: cuboid abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- Pathways Affected in Adenoid Cystic Carcinoma
- DNA methylation
- Epigenetic regulation of gene expression
Biological Process
- negative regulation of transcription by RNA polymerase II
- DNA repair
- ubiquitin-dependent protein catabolic process
- cell cycle
- cell population proliferation
Molecular Function
- proximal promoter sequence-specific DNA binding
- ubiquitin-protein transferase activity
- protein binding
- zinc ion binding
- methyl-CpG binding
Cellular Component
- nuclear chromatin
- euchromatin
- heterochromatin
- nucleus
- replication fork
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD- type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair. {ECO:0000269|PubMed:10646863, ECO:0000269|PubMed:15009091, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:17967883, ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:21777816, ECO:0000269|PubMed:22945642}.;
- Disease
- DISEASE: Note=Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression.;
Recessive Scores
- pRec
- 0.153
Essentials
- Indispensability pred.
- E
- Indispensability score
- 0.846