UCHL5
protein-codingubiquitin C-terminal hydrolase L5, the group of Ubiquitin C-terminal hydrolases|INO80 complex
Gene summary
Enables cysteine-type deubiquitinase activity; endopeptidase inhibitor activity; and proteasome binding activity. Involved in several processes, including negative regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of smoothened signaling pathway; and regulation of DNA metabolic process. Located in cytosol and nuclear lumen. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.8 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 UCHL5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001199261.3. 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 | 1 | 1 | ||||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 29 | 1 | 0 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001186190.1 | 11 | MANE Select | |
| Ensembl | ENSP00000356424.1 | 11 | MANE Select | |
| RefSeq | NP_001186191.1 | 11 | Standard | |
| RefSeq | NP_001186192.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| uchl5 | Danio rerio | Structure: pharyngeal arch cartilage Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-Ncore
- TGF-beta Signaling Pathway
- Signal Transduction
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- DNA repair
- DNA recombination
- ubiquitin-dependent protein catabolic process
- negative regulation of endopeptidase activity
- protein deubiquitination
Molecular Function
- RNA binding
- thiol-dependent ubiquitin-specific protease activity
- endopeptidase inhibitor activity
- protein binding
- proteasome binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367455
- Coding exons
- 11
- Length
- 47858
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.94 | 99 | 170 | 0.582 | 0.00000791 | 2192 |
| Missense (PolyPhen) | 20 | 57.752 | 0.34631 | 759 | ||
| Synonymous | 0.0100 | 59 | 59.1 | 0.998 | 0.00000301 | 550 |
| Loss of Function | 2.76 | 9 | 23.4 | 0.385 | 0.00000121 | 278 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000056 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.00013 | 0.000098 | rare |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1. {ECO:0000269|PubMed:16906146, ECO:0000269|PubMed:18922472}.;
Recessive Scores
- pRec
- 0.137
Intolerance Scores
- LoFtool
- 0.683
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.961
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |