USP28

Chr 11

ubiquitin specific peptidase 28

NCBI Gene: 57646 ENSG00000048028 UniProt: Q96RU2 OMIM: 610748

The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers. [provided by RefSeq, Oct 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 3.93

OE 0.48 (0.36–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.18Z-score

OE missense 0.86 (0.80–0.93)

484 obs / 562.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.36–0.65)

0≤0.351.4

Missense OE?0.86 (0.80–0.93)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 32 / 66.7Missense obs/exp: 484 / 562.6Syn Z: 0.54

Background carrier burden — how many people carry a rare variant somewhere in USP28?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,354 rare PASS variants

Rare truncating (LoF)

1 in 420

277 rare PASS variants

Rare synonymous (reference)

1 in 100

473 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for USP28. 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 53	1 in 780
South Asian	~43k	1 in 58	1 in 350
Remaining (unassigned)	~30k	1 in 51	1 in 480
European (Finnish)	~27k	1 in 110	1 in 1,600
Admixed American	~22k	1 in 46	1 in 430
African / African American	~21k	1 in 44	1 in 290
East Asian	~20k	1 in 61	1 in 600
Ashkenazi Jewish	~13k	1 in 120	1 in 890
Middle Eastern	~2,884	1 in 77	≈ 1 in 2,900

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.