USP19

Chr 3

ubiquitin specific peptidase 19

Also known as: ZMYND9

NCBI Gene: 10869ENSG00000172046UniProt: O94966

Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This protein is a ubiquitin protein ligase and plays a role in muscle wasting. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— USP19
⚡
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.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.20LOEUF
pLI 1.000
Z-score 6.66
OE 0.11 (0.06–0.20)
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.
1.99Z-score
OE missense 0.81 (0.76–0.86)
691 obs / 854.7 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.0.11 (0.06–0.20)
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 (0.76–0.86)
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.0.89
0≤1.21.6
LoF obs/exp: 7 / 64.9Missense obs/exp: 691 / 854.7Syn Z: 1.63

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

USP19 · 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
USP19 potentiates autophagic cell death via inhibiting mTOR pathway through deubiquitinating NEK9 in pancreatic cancer.
Wang G et al.·Cell Death Differ
2025
Suppression of Hepatocyte Ferroptosis via USP19-Mediated Deubiquitination of SLC7A11 in Ischemia-Free Liver Transplantation.
Xu J et al.·Adv Sci (Weinh)
2025
USP19 regulates DNA methylation damage repair and confers temozolomide resistance through MGMT stabilization.
Liu J et al.·CNS Neurosci Ther
2024
Deubiquitinase USP19 enhances phenylalanine hydroxylase protein stability and its enzymatic activity.
Sarodaya N et al.·Cell Biol Toxicol
2023
USP19 Suppresses Th17-Driven Pathogenesis in Autoimmunity.
Zhang J et al.·J Immunol
2021
Ubiquitin-specific protease 19 regulates the stability of the E3 ubiquitin ligase MARCH6.
Nakamura N et al.·Exp Cell Res
2014
USP19 exerts a tumor-promoting role in diffuse large B cell lymphoma through stabilizing PARK7.
Li Y et al.·FEBS J
2024
Concurrent inactivating mutations and expression losses of RGS2, HNF1A, and CAPN12 candidate tumor suppressor genes in colon cancers.
Kim JW et al.·Pathol Res Pract
2023
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
Rheumatoid ArthritisOsteoarthritisSarcopenia

Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study

NOT YET RECRUITING
NCT06480643Phase NAAmsterdam UMC, location VUmcStarted 2024-12-01
High load exercise typeLow load exercise type

External Resources

Links to major genomics databases and tools