UHRF2

Chr 9

ubiquitin like with PHD and ring finger domains 2

Also known as: NIRF, RNF107, TDRD23, URF2

NCBI Gene: 115426ENSG00000147854UniProt: Q96PU4

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]

0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— UHRF2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.24LOEUF
pLI 0.999
Z-score 5.37
OE 0.12 (0.06–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.32Z-score
OE missense 0.55 (0.50–0.62)
244 obs / 440.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.06–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.50–0.62)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25
0≤1.21.6
LoF obs/exp: 5 / 43.0Missense obs/exp: 244 / 440.0Syn Z: -2.44

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

UHRF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
UHRF2 promotes the malignancy of hepatocellular carcinoma by PARP1 mediated autophagy.
Zhang Y et al.·Cell Signal
2023
UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1.
Liu X et al.·Mol Cell
2021
UHRF2 promotes Hepatocellular Carcinoma Progression by Upregulating ErbB3/Ras/Raf Signaling Pathway.
Sun J et al.·Int J Med Sci
2021
The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory.
Chen R et al.·J Biol Chem
2017Functional
HBx promotes hepatocarcinogenesis by enhancing phosphorylation and blocking ubiquitinylation of UHRF2.
Cheng F et al.·Hepatol Int
2021
Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.
Wang Y et al.·Genome Med
2025Cohort
Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma.
Iguchi T et al.·Oncology
2018
Identification of an EMT-related gene-based prognostic signature in osteosarcoma.
Gong H et al.·Cancer Med
2023
PCNP promotes hepatocellular carcinoma progression by upregulating UHRF2 to activate ErbB3/Ras/Raf pathway.
Luo J et al.·Sci Rep
2025
Construction and validation of a novel gene signature for predicting the prognosis of osteosarcoma.
Yang J et al.·Sci Rep
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools