USP24
protein-codingubiquitin specific peptidase 24, the group of Ubiquitin specific peptidases
Gene summary
Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP24 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~149.0 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 USP24 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015306.3. 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 | 6 | 1 | 4 | 11 | ||
| missense | 233 | 4 | 1 | 238 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 252 | 5 | 5 | 262 |
Highest pathogenic variant AF is 0.00000425199
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056121.2 | 68 | MANE Select | |
| Ensembl | ENSP00000294383.5 | 68 | MANE Select | |
| Ensembl | ENSP00000489026.2 | 68 | Standard | |
| Ensembl | ENSP00000489026.2 | 68 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp24 | Danio rerio | Structure: pharyngeal arch cartilage Quality: malformed 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
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000294383
- Coding exons
- 68
- Length
- 148755
- Individuals with no LoFs
- 125440
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125459
- p
- 0.0000757
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.99 | 759 | 1.26e+3 | 0.604 | 0.0000654 | 17022 |
| Missense (PolyPhen) | 140 | 358.1 | 0.39096 | 4915 | ||
| Synonymous | 0.616 | 438 | 455 | 0.963 | 0.0000242 | 4887 |
| Loss of Function | 10.2 | 14 | 149 | 0.0942 | 0.00000827 | 1906 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00014 | 0.00012 | rare |
| Latino/Admixed American | 0.000036 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000049 | 0.000046 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-specific protease that regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53. Plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron. {ECO:0000269|PubMed:23159851, ECO:0000269|PubMed:29695420}.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- RVIS EVS
- -2.16
- RVIS percentile EVS
- 1.44
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.359
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |