UHRF2

Chr 9

ubiquitin like with PHD and ring finger domains 2

Also known as: NIRF, RNF107, TDRD23, URF2

NCBI Gene: 115426ENSG00000147854UniProt: Q96PU4OMIM: 615211

This gene encodes an E3 ubiquitin ligase that regulates cell cycle progression, DNA methylation, histone modifications, and DNA repair through ubiquitination of various substrates including cyclins and DNA damage response proteins. The gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.25), indicating that mutations are likely to cause severe developmental consequences. However, no specific human disease phenotype has been definitively associated with UHRF2 mutations in the current literature.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.24
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.
📋
ClinVar Variants
153 unique Pathogenic / Likely Pathogenic· 66 VUS of 244 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.12 (0.06–0.24)
0≤0.351.4
Missense OE0.55 (0.50–0.62)
0≤0.61.4
Synonymous OE1.25
0≤1.21.6
LoF obs/exp: 5 / 43.0Missense obs/exp: 244 / 440.0Syn Z: -2.44
DN
0.2598th %ile
GOF
0.2895th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

244 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic147
Likely Pathogenic6
VUS66
Likely Benign4
147
Pathogenic
6
Likely Pathogenic
66
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
147
0
147
Likely Pathogenic
0
0
6
0
6
VUS
0
60
6
0
66
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Total0631591223

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients