USP24

Chr 1

ubiquitin specific peptidase 24

NCBI Gene: 23358 ENSG00000162402 UniProt: Q9UPU5

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.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOEUF 0.15

Clinical Summary— USP24

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 226 VUS of 300 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.09 (0.06–0.15)

0≤0.351.4

Missense OE?0.60 (0.57–0.64)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 14 / 148.6Missense obs/exp: 759 / 1256.3Syn Z: 0.62

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS226

Likely Benign5

Benign5

Likely Pathogenic

226

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	1	0	1
VUS	226	0	0	226
Likely Benign	4	0	1	5
Benign	1	0	4	5
Total	231	1	5	237

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap USP24 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →