USP50

Chr 15

ubiquitin specific peptidase 50

NCBI Gene: 373509 ENSG00000170236 UniProt: Q70EL3

Enables cysteine-type deubiquitinase activity. Involved in regulation of cell cycle G2/M phase transition. Acts upstream of or within several processes, including nuclear speck organization; positive regulation of NLRP3 inflammasome complex assembly; and positive regulation of interleukin-1 beta production. Located in centrosome; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.87

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.000

Z-score -1.52

OE 1.40 (1.00–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.39Z-score

OE missense 0.92 (0.81–1.04)

165 obs / 179.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.40 (1.00–1.87)

0≤0.351.4

Missense OE?0.92 (0.81–1.04)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 23 / 16.4Missense obs/exp: 165 / 179.7Syn Z: 0.19

Background carrier burden — how many people carry a rare variant somewhere in USP50?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

423 rare PASS variants

Rare truncating (LoF)

1 in 710

77 rare PASS variants

Rare synonymous (reference)

1 in 190

151 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for USP50. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 760
South Asian	~43k	1 in 190	1 in 590
Remaining (unassigned)	~30k	1 in 87	1 in 630
European (Finnish)	~27k	1 in 380	1 in 1,300
Admixed American	~22k	1 in 87	1 in 560
African / African American	~21k	1 in 140	1 in 400
East Asian	~20k	1 in 130	1 in 830
Ashkenazi Jewish	~13k	1 in 570	none seen
Middle Eastern	~2,884	1 in 220	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓