USP10

Chr 16

ubiquitin specific peptidase 10

Also known as: UBPO

NCBI Gene: 9100 ENSG00000103194 UniProt: Q8NFA0 OMIM: 609818

This gene encodes a deubiquitinase that removes ubiquitin from target proteins and acts as a positive regulator of mTORC1 signaling by deubiquitinating LAMTOR1 to promote lysosomal function. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.28), suggesting mutations would likely cause severe developmental disorders. Specific disease associations and inheritance patterns for USP10 mutations have not yet been established in the clinical literature.

OMIM ResearchSummary from RefSeq, UniProt

Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.28

Clinical Summary— USP10

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

139 VUS of 168 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.994

Z-score 4.90

OE 0.13 (0.07–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

-0.67Z-score

OE missense 1.09 (1.01–1.17)

494 obs / 453.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.28)

0≤0.351.4

Missense OE?1.09 (1.01–1.17)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 5 / 37.3Missense obs/exp: 494 / 453.6Syn Z: -2.29

This gene — mechanism propensity

0.3495th %ile

GOF

0.4382th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

168 submitted variants in ClinVar

ClinVar

Classification Summary

VUS139

Likely Benign9

139

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	139	0	139
Likely Benign	8	1	9
Benign	0	0	0
Total	147	1	148

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap USP10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →