USP51
protein-codingubiquitin specific peptidase 51, the group of Ubiquitin specific peptidases
Gene summary
Enables chromatin binding activity; deubiquitinase activity; and histone binding activity. Involved in DNA repair-dependent chromatin remodeling; regulation of cell cycle process; and regulation of double-strand break repair. Predicted to be located in chromosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.2 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 USP51 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_201286.4. 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 | 2 | 3 | 1 | 6 | ||
| missense | 75 | 1 | 76 | |||
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 79 | 4 | 1 | 85 |
Highest pathogenic variant AF is 9.1673314e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_958443.1 | 1 | MANE Select | |
| Ensembl | ENSP00000423333.2 | 1 | MANE Select | |
| Ensembl | ENSP00000490435.1 | 2 | Standard | |
| Ensembl | ENSP00000603824.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- DNA repair
- ubiquitin-dependent protein catabolic process
- regulation of cell cycle process
- regulation of double-strand break repair via homologous recombination
- histone deubiquitination
Molecular Function
- chromatin binding
- thiol-dependent ubiquitin-specific protease activity
- zinc ion binding
- histone binding
Cellular Component
- chromosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000500968
- Coding exons
- 1
- Length
- 4587
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 5
- Defined
- 125746
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.13 | 203 | 254 | 0.800 | 0.0000173 | 4670 |
| Missense (PolyPhen) | 38 | 91.103 | 0.41711 | 1865 | ||
| Synonymous | -1.48 | 118 | 99.3 | 1.19 | 0.00000677 | 1384 |
| Loss of Function | 2.48 | 4 | 14.0 | 0.285 | 0.00000103 | 265 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00016 | 0.00012 | rare |
| Latino/Admixed American | 0.000037 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000065 | 0.000046 | rare |
| European (Non-Finnish) | 0.000026 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically deubiquitinates 'Lys-14' (H2AK13Ub) and 'Lys-16'(H2AK15Ub) of histone H2A regulating the DNA damage response at double-strand breaks (DSBs) (PubMed:27083998). USP51 is recruited to chromatin after DNA damage and regulates the dynamic assembly/disassembly of TP53BP1 and BRCA1. Exhibits also activity for 'Lys-27' or 'Lys-63'-linked di-ubiquitin (PubMed:27083998). {ECO:0000269|PubMed:27083998}.;
Recessive Scores
- pRec
- 0.0877
Intolerance Scores
- LoFtool
- 0.0619
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |