USP24

Chr 1

ubiquitin specific peptidase 24

NCBI Gene: 23358ENSG00000162402UniProt: Q9UPU5

Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP24 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]

249
ClinVar variants
12
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— USP24
⚡
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
12 Pathogenic / Likely Pathogenic· 227 VUS of 249 total submissions
Some data sources returned errors (2)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.15LOEUF
pLI 1.000
Z-score 10.23
OE 0.09 (0.06–0.15)
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.
4.99Z-score
OE missense 0.60 (0.57–0.64)
759 obs / 1256.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.09 (0.06–0.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.57–0.64)
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.0.96
0≤1.21.6
LoF obs/exp: 14 / 148.6Missense obs/exp: 759 / 1256.3Syn Z: 0.62

ClinVar Variant Classifications

249 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic4
VUS227
Likely Benign5
Benign5
8
Pathogenic
4
Likely Pathogenic
227
VUS
5
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
4
0
4
VUS
0
222
5
0
227
Likely Benign
0
4
0
1
5
Benign
0
1
0
4
5
Total0227175249

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

View in ClinVar →

Protein Context — Lollipop Plot

USP24 · 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
USP24 promotes hepatocellular carcinoma tumorigenesis through deubiquitinating and stabilizing TRAF2.
Zhou N et al.·Biochem Pharmacol
2024
USP24 upregulation stabilizes PKA-Cα to promote lipogenesis, inflammation, and fibrosis during MASH progression.
Ning B et al.·J Biomed Sci
2025
The combination of USP24-i-101-Astemizole sensitizes the cytotoxicity of Taxol and Gefitinib in drug-resistant lung cancer.
Young MJ et al.·Biomed Pharmacother
2025
Ubiquitin-specific protease 24: a potential anti-cancer target.
Ye L et al.·Biochem Biophys Res Commun
2025Review
USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway.
He H et al.·Int J Biol Sci
2021
Variants of ubiquitin-specific peptidase 24 play a crucial role in lung cancer malignancy.
Wang YC et al.·Oncogene
2016
Diagnostic yield and novel candidate genes by next generation sequencing in 166 children with intrahepatic cholestasis.
Zheng Y et al.·Hepatol Int
2024
EGF-mediated inhibition of ubiquitin-specific peptidase 24 expression has a crucial role in tumorigenesis.
Wang SA et al.·Oncogene
2017
Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort.
Ben-Mahmoud A et al.·Int J Mol Sci
2024Cohort
NCI677397 targeting USP24-mediated induction of lipid peroxidation induces ferroptosis in drug-resistant cancer cells.
Wang SA et al.·Mol Oncol
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.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools