DTX2

Chr 7

deltex E3 ubiquitin ligase 2

Also known as: RNF58

NCBI Gene: 113878ENSG00000091073UniProt: Q86UW9

DTX2 functions as an E3 ubiquitin ligase (Takeyama et al., 2003 [PubMed 12670957]).[supplied by OMIM, Nov 2009]

152
ClinVar variants
18
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— DTX2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 115 VUS of 152 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.57LOEUF
pLI 0.029
Z-score 3.09
OE 0.30 (0.17–0.57)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.93Z-score
OE missense 0.86 (0.79–0.95)
325 obs / 375.8 exp
Tolerant

Mild missense constraint

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.0.30 (0.17–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.79–0.95)
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.0.98
0≤1.21.6
LoF obs/exp: 7 / 23.0Missense obs/exp: 325 / 375.8Syn Z: 0.18

ClinVar Variant Classifications

152 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS115
Likely Benign13
Benign6
17
Pathogenic
1
Likely Pathogenic
115
VUS
13
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
1
0
1
VUS
0
107
8
0
115
Likely Benign
0
7
0
6
13
Benign
0
0
5
1
6
Total0114317152

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

View in ClinVar →

Protein Context — Lollipop Plot

DTX2 · 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
Targeting Deltex E3 Ubiquitin Ligase 2 Inhibits Tumor-associated Neutrophils and Sensitizes Hepatocellular Carcinoma Cells to Immunotherapy.
Wu X et al.·Adv Sci (Weinh)
2025
DTX2 promotes glioma development via regulation of HLTF.
Li R et al.·Biol Direct
2024
The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer.
Scalia P et al.·Cells
2023Review
Toxins of Okadaic Acid-Group Increase Malignant Properties in Cells of Colon Cancer.
Jiménez-Cárcamo D et al.·Toxins (Basel)
2020
Cancer stem cell gene profile as predictor of relapse in high risk stage II and stage III, radically resected colon cancer patients.
Giampieri R et al.·PLoS One
2013Cohort
[Simultaneous determination of 12 lipophilic shellfish toxins in plasma and urine by ultra-high performance liquid chromatography-tandem mass spectrometry].
Lin Q et al.·Se Pu
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
[High expression of DTX2 promotes proliferation, invasion and epithelial-mesenchymal transition of oxaliplatin-resistant colorectal cancer cells].
Ma Z et al.·Nan Fang Yi Ke Da Xue Xue Bao
2025
DTX2 attenuates Lenvatinib-induced ferroptosis by suppressing docosahexaenoic acid biosynthesis through HSD17B4-dependent peroxisomal β-oxidation in hepatocellular carcinoma.
Zhang Z et al.·Drug Resist Updat
2025
Targeting DTX2/UFD1-mediated FTO degradation to regulate antitumor immunity.
Cui YH et al.·Proc Natl Acad Sci U S A
2024🔓 Open Access
E3 ubiquitin ligase DTX2 fosters ferroptosis resistance via suppressing NCOA4-mediated ferritinophagy in non-small cell lung cancer.
Liu Z et al.·Drug Resist Updat
2024
Bioavailability profiling shows differences in OA, DTX1 and DTX2 toxins that justify their toxicity.
Rodríguez-Santos L et al.·Chemosphere
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools