USP42

Chr 7

ubiquitin specific peptidase 42

NCBI Gene: 84132ENSG00000106346UniProt: Q9H9J4

Enables cysteine-type deubiquitinase activity. Predicted to be involved in protein deubiquitination; regulation of apoptotic process; and regulation of protein stability. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

289
ClinVar variants
16
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— USP42
⚡
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
16 Pathogenic / Likely Pathogenic· 246 VUS of 289 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.13LOEUF
pLI 1.000
Z-score 6.10
OE 0.04 (0.02–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
-1.63Z-score
OE missense 1.16 (1.10–1.23)
916 obs / 787.2 exp
Tolerant

Tolerant to missense variation

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.0.04 (0.02–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.16 (1.10–1.23)
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: 2 / 47.2Missense obs/exp: 916 / 787.2Syn Z: -3.61

ClinVar Variant Classifications

289 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS246
Likely Benign27
15
Pathogenic
1
Likely Pathogenic
246
VUS
27
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
243
3
0
246
Likely Benign
0
24
0
3
27
Benign
0
0
0
0
0
Total0267193289

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

View in ClinVar →

Protein Context — Lollipop Plot

USP42 · 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
Pediatric acute myeloid leukemia with t(7;21)(p22;q22).
Paulraj P et al.·Genes Chromosomes Cancer
2019Review
Myeloid leukemia with t(7;21)(p22;q22) and 5q deletion.
Panagopoulos I et al.·Oncol Rep
2013Case report
PopCluster: an algorithm to identify genetic variants with ethnicity-dependent effects.
Gurinovich A et al.·Bioinformatics
2019
Detection of rare reciprocal RUNX1 rearrangements by next-generation sequencing in acute myeloid leukemia.
Flach J et al.·Genes Chromosomes Cancer
2020Case report
A cytogenetic study of 397 consecutive acute myeloid leukemia cases identified three with a t(7;21) associated with 5q abnormalities and exhibiting similar clinical and biological features, suggesting a new, rare acute myeloid leukemia entity.
Jeandidier E et al.·Cancer Genet
2012Case report
Gefitinib Combined with Cetuximab for the Treatment of Lung Adenocarcinoma Harboring the EGFR-Intergenic Region (SEC61G) Fusion and EGFR Amplification.
Zhang G et al.·Oncologist
2021Case report
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.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools