USP22

Chr 17

ubiquitin specific peptidase 22

Also known as: USP3L

USP22 encodes a deubiquitinase that removes ubiquitin from histones H2A and H2B as part of the SAGA transcriptional complex and regulates cell cycle progression, immune signaling, and gene expression. Mutations cause autosomal recessive intellectual disability with seizures and microcephaly, typically presenting in early childhood. The gene shows significant constraint against loss-of-function variants (LOEUF 0.415), indicating intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.41
Clinical SummaryUSP22
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.41LOEUF
pLI 0.552
Z-score 3.91
OE 0.21 (0.110.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.56Z-score
OE missense 0.43 (0.370.49)
130 obs / 305.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.21 (0.110.41)
00.351.4
Missense OE0.43 (0.370.49)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 6 / 28.6Missense obs/exp: 130 / 305.1Syn Z: 1.20

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

USP22 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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