USP21
protein-codingubiquitin specific peptidase 21, the group of Ubiquitin specific peptidases
Gene summary
This gene encodes a member of the C19 peptidase family, also known as family 2 of ubiquitin carboxy-terminal hydrolases. The encoded protein cleaves ubiquitin from ubiquitinated proteins for recycling in intracellular protein degradation. The encoded protein is also able to release NEDD8, a ubiquitin-like protein, from NEDD8-conjugated proteins. This gene has been referred to as USP16 and USP23 but is now known as USP21. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
- USP23
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.3 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 USP21 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001014443.3. 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 | 79 | 79 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 85 | 1 | 0 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001014443.1 | 12 | MANE Select | |
| Ensembl | ENSP00000356981.3 | 12 | MANE Select | |
| RefSeq | NP_001306776.1 | 13 | Standard | |
| RefSeq | NP_001306777.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Necroptosis - Homo sapiens (human)
- Signal Transduction
- Post-translational protein modification
- Metabolism of proteins
- TNFR1-induced NFkappaB signaling pathway
Biological Process
- ubiquitin-dependent protein catabolic process
- histone deubiquitination
- protein deubiquitination
- neuron projection development
- positive regulation of transcription, DNA-templated
Molecular Function
- transcription coactivator activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- cysteine-type peptidase activity
- NEDD8-specific protease activity
Cellular Component
- cellular_component
- nucleoplasm
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368002
- Coding exons
- 12
- Length
- 6274
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.08 | 250 | 361 | 0.692 | 0.0000241 | 3569 |
| Missense (PolyPhen) | 60 | 114.22 | 0.5253 | 1246 | ||
| Synonymous | 0.430 | 124 | 130 | 0.952 | 0.00000656 | 1265 |
| Loss of Function | 3.97 | 12 | 38.6 | 0.311 | 0.00000315 | 295 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A releaves the repression of di- and trimethylation of histone H3 at 'Lys-4', resulting in regulation of transcriptional initiation. Regulates gene expression via histone H2A deubiquitination (By similarity). Also capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates (PubMed:10799498). Deubiquitinates BAZ2A/TIP5 leading to its stabilization (PubMed:26100909). {ECO:0000250|UniProtKB:Q9QZL6, ECO:0000269|PubMed:10799498, ECO:0000269|PubMed:26100909}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.653
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.34
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.963
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |