USP43
protein-codingubiquitin specific peptidase 43, the group of Ubiquitin specific peptidases
Gene summary
Predicted to enable ISG15-specific peptidase activity. Predicted to be involved in translesion synthesis. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~85.0 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 USP43 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153210.5. 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 | 1 | 2 | 4 | ||
| missense | 145 | 15 | 1 | 161 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 149 | 16 | 3 | 168 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_694942.3 | 15 | MANE Select | |
| Ensembl | ENSP00000285199.6 | 15 | MANE Select | |
| RefSeq | NP_001254505.1 | 15 | Standard | |
| Ensembl | ENSP00000458963.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp43a | Danio rerio | Structure: post-vent region Quality: curled abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA Repair
- Termination of translesion DNA synthesis
- Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
- DNA Damage Bypass
Biological Process
- ubiquitin-dependent protein catabolic process
- protein deubiquitination
- translesion synthesis
Molecular Function
- ISG15-specific protease activity
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000285199
- Coding exons
- 15
- Length
- 84994
- Individuals with no LoFs
- 124631
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 124658
- p
- 0.000108
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.58 | 468 | 575 | 0.814 | 0.0000329 | 7149 |
| Missense (PolyPhen) | 76 | 156.04 | 0.48706 | 2055 | ||
| Synonymous | 1.65 | 209 | 242 | 0.865 | 0.0000144 | 2355 |
| Loss of Function | 4.76 | 11 | 45.7 | 0.241 | 0.00000257 | 516 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00045 | 0.00045 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.000097 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May recognize and hydrolyze the peptide bond at the C- terminal Gly of ubiquitin. Involved in the processing of poly- ubiquitin precursors as well as that of ubiquitinated proteins (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0941
Intolerance Scores
- LoFtool
- 0.688
- RVIS EVS
- -0.81
- RVIS percentile EVS
- 12.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.675
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |