USP22
protein-codingubiquitin specific peptidase 22, the group of Ubiquitin specific peptidases|SAGA complex
Gene summary
Enables deubiquitinase activity; enzyme binding activity; and transcription coactivator activity. Contributes to histone H4 acetyltransferase activity. Involved in several processes, including G2/M transition of mitotic cell cycle; protein deubiquitination; and regulation of gene expression. Part of SAGA complex. [provided by Alliance of Genome Resources, Jul 2025]
- USP3L
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to USP22 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015276.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 36 | 1 | 37 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 38 | 1 | 0 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056091.1 | 13 | MANE Select | |
| Ensembl | ENSP00000261497.4 | 13 | MANE Select | |
| Ensembl | ENSP00000468457.1 | 3 | Standard | |
| Ensembl | ENSP00000440950.2 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp22 | Danio rerio | Structure: brain Quality: bulbous abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Chromatin modifying enzymes
- HATs acetylate histones
- Ub-specific processing proteases
Biological Process
- ubiquitin-dependent protein catabolic process
- cell cycle
- embryo development ending in birth or egg hatching
- histone ubiquitination
- histone deubiquitination
Molecular Function
- transcription coactivator activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- zinc ion binding
- H4 histone acetyltransferase activity
Cellular Component
- SAGA complex
- nucleoplasm
- nuclear speck
- SAGA-type complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261497
- Coding exons
- 13
- Length
- 44164
- Individuals with no LoFs
- 124788
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 124796
- p
- 0.0000321
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.56 | 130 | 305 | 0.426 | 0.0000180 | 3472 |
| Missense (PolyPhen) | 24 | 108.75 | 0.22069 | 1274 | ||
| Synonymous | 1.20 | 111 | 128 | 0.865 | 0.00000872 | 941 |
| Loss of Function | 3.91 | 6 | 28.6 | 0.210 | 0.00000154 | 323 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000055 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Histone deubiquitinating component of the transcription regulatory histone acetylation (HAT) complex SAGA. Catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a coactivator. Recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation and cell cycle progression. {ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:18206973, ECO:0000269|PubMed:18469533}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.153
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.755
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |