USP19
protein-codingubiquitin specific peptidase 19, the group of Ubiquitin specific peptidases|Zinc fingers MYND-type
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 protein is a ubiquitin protein ligase and plays a role in muscle wasting. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.9 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 USP19 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001199161.2. 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 | 4 | 1 | 1 | 6 | ||
| missense | 2 | 188 | 16 | 206 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 2 | 0 | 194 | 17 | 1 | 214 |
Highest pathogenic variant AF is 0.000029166496
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001186090.1 | 26 | MANE Select | |
| Ensembl | ENSP00000395260.1 | 26 | MANE Select | |
| RefSeq | NP_001186089.1 | 26 | Standard | |
| RefSeq | NP_001186091.1 | 26 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp19 | 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
- Ub-specific processing proteases
- Deubiquitination
Biological Process
- protein deubiquitination
- ubiquitin-dependent ERAD pathway
- regulation of protein stability
- response to endoplasmic reticulum stress
- negative regulation of skeletal muscle tissue development
Molecular Function
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- ubiquitin protein ligase binding
- thiol-dependent ubiquitinyl hydrolase activity
- metal ion binding
Cellular Component
- endoplasmic reticulum membrane
- cytosol
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000434032
- Coding exons
- 26
- Length
- 12893
- Individuals with no LoFs
- 124790
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 124802
- p
- 0.0000481
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.99 | 691 | 855 | 0.808 | 0.0000532 | 9131 |
| Missense (PolyPhen) | 219 | 331.42 | 0.66078 | 3515 | ||
| Synonymous | 1.63 | 298 | 336 | 0.887 | 0.0000198 | 2966 |
| Loss of Function | 6.66 | 7 | 64.9 | 0.108 | 0.00000332 | 733 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.000032 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000038 | 0.000035 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin- dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic- reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non- catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked ubiquitin chains. {ECO:0000269|PubMed:19465887, ECO:0000269|PubMed:21849505, ECO:0000269|PubMed:22128162, ECO:0000269|PubMed:22689415}.;
Intolerance Scores
- LoFtool
- 0.318
- RVIS EVS
- -1.59
- RVIS percentile EVS
- 3.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.672
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |