USP34
protein-codingubiquitin specific peptidase 34, the group of Ubiquitin specific peptidases|Armadillo like helical domain containing|Small nucleolar RNA protein coding host genes
Gene summary
Enables cysteine-type deubiquitinase activity and cysteine-type endopeptidase activity. Involved in positive regulation of canonical Wnt signaling pathway and protein K48-linked deubiquitination. Predicted to be active in cytosol and nucleus. [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 ~283.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*USP34* was first reported in relation to autosomal dominant congenital heart disease in 2013 (Zaidi et al., PMID: 23665959). Three unique variants (missense) that have been reported in 3 probands in 3 publications (PMIDs: 23665959, 29555671, 32368696) are included in this curation. The mechanism of pathogenicity is unknown. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the Congenital Heart Disease GCEP on June 10th, 2024 (SOP Version 10).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to USP34 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014709.4. 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 | 8 | 14 | 2 | 24 | ||
| missense | 469 | 1 | 3 | 473 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 15 | 15 | ||||
| Total | 0 | 0 | 492 | 15 | 5 | 512 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055524.3 | 80 | MANE Select | |
| Ensembl | ENSP00000381577.2 | 80 | MANE Select | |
| Ensembl | ENSP00000398960.1 | 26 | Standard | |
| Ensembl | ENSP00000398489.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by WNT
- Signal Transduction
- Post-translational protein modification
- Metabolism of proteins
- Ub-specific processing proteases
Biological Process
- ubiquitin-dependent protein catabolic process
- Wnt signaling pathway
- protein deubiquitination
- regulation of protein stability
- protein K48-linked deubiquitination
Molecular Function
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398571
- Coding exons
- 80
- Length
- 283307
- Individuals with no LoFs
- 124757
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 124785
- p
- 0.000112
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.34 | 1513 | 1.79e+3 | 0.844 | 0.0000905 | 23551 |
| Missense (PolyPhen) | 255 | 517.94 | 0.49233 | 7045 | ||
| Synonymous | -5.27 | 784 | 617 | 1.27 | 0.0000318 | 6361 |
| Loss of Function | 12.4 | 11 | 200 | 0.0550 | 0.0000109 | 2470 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00016 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00035 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes 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. {ECO:0000269|PubMed:21383061}.;
Recessive Scores
- pRec
- 0.0952
Intolerance Scores
- LoFtool
- 0.111
- RVIS EVS
- -3.59
- RVIS percentile EVS
- 0.3
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.777
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |