USP12
protein-codingubiquitin specific peptidase 12, the group of Ubiquitin specific peptidases
Gene summary
Enables cysteine-type deubiquitinase activity and cysteine-type endopeptidase activity. Involved in protein deubiquitination. Located in cytoplasm; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
- USP12L1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~105.7 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 USP12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182488.4. 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 | 3 | 1 | 4 | |||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 31 | 1 | 0 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_872294.2 | 9 | MANE Select | |
| Ensembl | ENSP00000282344.6 | 9 | MANE Select | |
| Ensembl | ENSP00000480395.1 | 3 | Standard | |
| Ensembl | ENSP00000478929.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp12b | Danio rerio | Structure: post-vent region Quality: necrotic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Ub-specific processing proteases
- Deubiquitination
Biological Process
- ubiquitin-dependent protein catabolic process
- protein deubiquitination
Molecular Function
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- thiol-dependent ubiquitinyl hydrolase activity
- metal ion binding
Cellular Component
- cellular_component
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000282344
- Coding exons
- 9
- Length
- 105741
- Individuals with no LoFs
- 125650
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125656
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.82 | 90 | 203 | 0.443 | 0.0000110 | 2465 |
| Missense (PolyPhen) | 4 | 64.323 | 0.062186 | 868 | ||
| Synonymous | 0.629 | 63 | 69.7 | 0.904 | 0.00000376 | 655 |
| Loss of Function | 3.70 | 2 | 19.7 | 0.101 | 9.63e-7 | 258 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000039 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deubiquitinating enzyme. Has almost no deubiquitinating activity by itself and requires the interaction with WDR20 and WDR48 to have a high activity (PubMed:19075014, PubMed:27373336). Not involved in deubiquitination of monoubiquitinated FANCD2 (PubMed:19075014). In complex with WDR48, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035). {ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:24145035, ECO:0000269|PubMed:27373336}.;
Intolerance Scores
- LoFtool
- 0.441
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.881
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |