UHRF1
Overview
UHRF1 (Ubiquitin Like With PHD And Ring Finger Domains 1, also known as ICBP90 or NP95) encodes an E3 ubiquitin ligase that acts as a key epigenetic regulator: it binds hemi-methylated DNA via its SRA domain and recruits DNMT1 to maintain DNA methylation patterns during replication. UHRF1 also participates in the p53-dependent DNA-damage checkpoint through its RING-domain ubiquitin ligase activity. It is overexpressed in many cancers and acts as an oncogene in that context, but genomic loss or mutation can also impair the checkpoint surveillance function, representing a distinct tumor-suppressive mechanism.
Alterations observed in the corpus
- 2 somatic mutations plus 3 homozygous deletions observed in 8% of adenoid cystic carcinoma (ACC) in a WGS discovery cohort; described as a p53-dependent DNA-damage checkpoint ubiquitin ligase — alterations are consistent with loss-of-function in a checkpoint gene PMID:23685749
Cancer types (linked)
- ACC (adenoid cystic carcinoma): mutation + homozygous deletion in 8% of discovery cohort cases; co-occurring with TP53 mutation in the same tumor landscape PMID:23685749
Co-occurrence and mutual exclusivity
Therapeutic relevance
- No specific therapeutic agent targeting UHRF1 reported in the corpus. UHRF1 inhibition is under pre-clinical investigation as an anti-cancer strategy in other tumor types via disruption of epigenetic maintenance, but direct implications for ACC have not been tested.
Open questions
- The 3 homozygous deletions at 8% frequency in a small ACC cohort (n=24 WGS) require validation in larger series to confirm UHRF1 as a bona fide recurrent driver rather than a passenger alteration.
- Whether UHRF1 loss cooperates with MYB-NFIB fusion (the dominant ACC driver) in the same tumors or defines a distinct molecular subgroup is not resolved.
Sources
This page was processed by entity-page-writer on 2026-05-09.