USP2

Chr 11

ubiquitin specific peptidase 2

Also known as: UBP41, USP9

NCBI Gene: 9099 ENSG00000036672 UniProt: O75604

This gene encodes a member of the family of de-ubiquitinating enzymes, which belongs to the peptidase C19 superfamily. The encoded protein is a ubiquitin-specific protease which is required for TNF-alpha (tumor necrosis factor alpha) -induced NF-kB (nuclear factor kB) signaling. This protein deubiquitinates polyubiquitinated target proteins such as fatty acid synthase, murine double minute 2 (MDM2), MDM4/MDMX and cyclin D1. MDM2 and MDM4 are negative regulators of the p53 tumor suppressor and cyclin D1 is required for cell cycle G1/S transition. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

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

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.001

Z-score 3.60

OE 0.34 (0.22–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.22Z-score

OE missense 0.82 (0.75–0.90)

306 obs / 372.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.22–0.56)

0≤0.351.4

Missense OE?0.82 (0.75–0.90)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 12 / 35.0Missense obs/exp: 306 / 372.5Syn Z: -0.11

Background carrier burden — how many people carry a rare variant somewhere in USP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 65

825 rare PASS variants

Rare truncating (LoF)

1 in 680

98 rare PASS variants

Rare synonymous (reference)

1 in 120

350 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for USP2. 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 99	1 in 660
South Asian	~43k	1 in 63	1 in 520
Remaining (unassigned)	~30k	1 in 49	1 in 420
European (Finnish)	~27k	1 in 410	1 in 510
Admixed American	~22k	1 in 57	1 in 850
African / African American	~21k	1 in 66	1 in 320
East Asian	~20k	1 in 75	1 in 840
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 59	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 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓