USP24

Chr 1

ubiquitin specific peptidase 24

USP24 encodes a deubiquitinating enzyme that cleaves ubiquitin from target proteins to regulate their stability, including proteins involved in DNA damage response (DDB2, TP53), cell survival (MCL1), and iron metabolism through ferritinophagy. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.147), suggesting mutations would likely cause severe developmental effects, though specific disease associations have not yet been established. Current evidence suggests autosomal inheritance patterns would be expected for any associated disorders.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.15
Clinical SummaryUSP24
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 unique Pathogenic / Likely Pathogenic· 231 VUS of 316 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 10.23
OE 0.09 (0.060.15)
Highly constrained

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

Missense Constraint
4.99Z-score
OE missense 0.60 (0.570.64)
759 obs / 1256.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.09 (0.060.15)
00.351.4
Missense OE0.60 (0.570.64)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 14 / 148.6Missense obs/exp: 759 / 1256.3Syn Z: 0.62

ClinVar Variant Classifications

316 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic4
VUS231
Likely Benign5
Benign5
8
Pathogenic
4
Likely Pathogenic
231
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
226
5
0
231
Likely Benign
0
4
0
1
5
Benign
0
1
0
4
5
Total0231175253

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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