USP11
protein-codingubiquitin specific peptidase 11, the group of Ubiquitin specific peptidases
Gene summary
Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23 [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 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 USP11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001371072.1. 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 | 1 | 13 | 6 | 8 | 28 | |
| missense | 1 | 93 | 3 | 1 | 98 | |
| nonsense | 9 | 9 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 26 | 26 | ||||
| Total | 0 | 2 | 141 | 9 | 9 | 161 |
Highest pathogenic variant AF is 0.0000140499005
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001358001.1 | 21 | MANE Select | |
| Ensembl | ENSP00000366311.2 | 21 | MANE Select | |
| Ensembl | ENSP00000218348.3 | 21 | Standard | |
| Ensembl | ENSP00000218348.3 | 21 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp11 | Danio rerio | Structure: post-vent region Quality: curled abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Chaperonin-mediated protein folding
- Association of TriC/CCT with target proteins during biosynthesis
- Ub-specific processing proteases
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
Cellular Component
- nucleus
- nucleoplasm
- chromosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000218348
- Coding exons
- 21
- Length
- 15639
- Individuals with no LoFs
- 125510
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125512
- p
- 0.00000797
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.57 | 225 | 435 | 0.518 | 0.0000379 | 6324 |
| Missense (PolyPhen) | 65 | 197.84 | 0.32855 | 2795 | ||
| Synonymous | -0.811 | 194 | 180 | 1.08 | 0.0000159 | 1892 |
| Loss of Function | 5.38 | 2 | 37.6 | 0.0532 | 0.00000283 | 572 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000079 | 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 | 0.0 | absent |
| South Asian | 0.000053 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains (PubMed:12084015, PubMed:15314155, PubMed:17897950, PubMed:19874889, PubMed:20233726, PubMed:24724799). Inhibits the degradation of target proteins by the proteasome (PubMed:12084015). Cleaves preferentially 'Lys-6' and 'Lys-63'-linked ubiquitin chains. Has lower activity with 'Lys-11' and 'Lys-33'-linked ubiquitin chains, and extremely low activity with 'Lys-27', 'Lys-29' and 'Lys-48'- linked ubiquitin chains (in vitro) (PubMed:24724799). Plays a role in the regulation of pathways leading to NF-kappa-B activation (PubMed:17897950, PubMed:19874889). Plays a role in the regulation of DNA repair after double-stranded DNA breaks (PubMed:15314155, PubMed:20233726). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:20601937). {ECO:0000269|PubMed:15314155, ECO:0000269|PubMed:17897950, ECO:0000269|PubMed:18408009, ECO:0000269|PubMed:19874889, ECO:0000269|PubMed:20233726, ECO:0000269|PubMed:24724799}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.172
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.71
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.594
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |