USP43

Chr 17

ubiquitin specific peptidase 43

NCBI Gene: 124739ENSG00000154914UniProt: Q70EL4

Predicted to enable ISG15-specific peptidase activity. Predicted to be involved in translesion synthesis. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

0
ClinVar variants
0
Pathogenic / LP
0.16
pLI score
0
Active trials
Clinical Summary— USP43
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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.
0.40LOEUF
pLI 0.164
Z-score 4.76
OE 0.24 (0.15–0.40)
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.
1.58Z-score
OE missense 0.81 (0.75–0.88)
468 obs / 574.8 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.0.24 (0.15–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.75–0.88)
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.0.87
0≤1.21.6
LoF obs/exp: 11 / 45.7Missense obs/exp: 468 / 574.8Syn Z: 1.65

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

USP43 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
USP43 stabilizes c-Myc to promote glycolysis and metastasis in bladder cancer.
Li M et al.·Cell Death Dis
2024
The USP43/RNF2 axis negatively regulates antiviral innate immunity by promoting TBK1 ubiquitination and degradation.
Zhao X et al.·Cell Death Differ
2025
YY1-induced USP43 drives ferroptosis suppression by FASN stabilization and subsequent activation of SLC7A11 in ovarian cancer.
Zhao T et al.·Cell Death Dis
2025
Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.
Pauzaite T et al.·EMBO J
2024
USP43 drives cervical carcinoma progression through regulation of the Hippo/TAZ pathway.
Zhang Y et al.·Int Immunopharmacol
2025
The mechanism of USP43 in the development of tumor: a literature review.
Zhao Z et al.·Aging (Albany NY)
2024Review
Prognostic Value and Oncogenic Effects of Ubiquitin-Specific Protease 43 in Lung Squamous Cell Carcinoma.
Sun Q et al.·Tohoku J Exp Med
2022
USP43-mediated HSPA8 deubiquitination alleviates diabetic kidney disease.
Yang G et al.·Biochem Biophys Res Commun
2025
Effect of ubiquitin-specific proteinase 43 on ovarian serous adenocarcinoma and its clinical significance.
Li Q et al.·J Obstet Gynaecol
2024
USP43 impairs cisplatin sensitivity in epithelial ovarian cancer through HDAC2-dependent regulation of Wnt/β-catenin signaling pathway.
Pei L et al.·Apoptosis
2024
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