USP39
protein-codingubiquitin specific peptidase 39, the group of Ubiquitin specific peptidases|tri-snRP complex
Gene summary
Predicted to enable cysteine-type deubiquitinase activity and zinc ion binding activity. Involved in spliceosomal complex assembly. Located in nucleoplasm. Part of U4/U6 x U5 tri-snRNP complex. [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 ~46.4 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 USP39 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006590.4. 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 | 2 | 1 | 3 | |||
| missense | 65 | 1 | 66 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 71 | 2 | 0 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006581.2 | 13 | MANE Select | |
| Ensembl | ENSP00000312981.6 | 13 | MANE Select | |
| RefSeq | NP_001243654.1 | 13 | Standard | |
| RefSeq | NP_001243655.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp39 | Danio rerio | Structure: proximal pars anterior Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spliceosome - Homo sapiens (human)
- Metabolism of RNA
- mRNA Splicing - Major Pathway
- mRNA Splicing
- Processing of Capped Intron-Containing Pre-mRNA
Biological Process
- spliceosomal complex assembly
- mRNA splicing, via spliceosome
- mRNA processing
- cell cycle
- RNA splicing
Molecular Function
- zinc ion binding
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- nucleus
- nucleoplasm
- spliceosomal complex
- U4/U6 x U5 tri-snRNP complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000323701
- Coding exons
- 13
- Length
- 46425
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.70 | 227 | 312 | 0.728 | 0.0000166 | 3703 |
| Missense (PolyPhen) | 59 | 137.16 | 0.43016 | 1610 | ||
| Synonymous | -0.479 | 129 | 122 | 1.06 | 0.00000656 | 1080 |
| Loss of Function | 3.45 | 9 | 29.0 | 0.310 | 0.00000148 | 345 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in pre-mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the precatalytic spliceosome (PubMed:11350945, PubMed:26912367). Regulates AURKB mRNA levels, and thereby plays a role in cytokinesis and in the spindle checkpoint. Does not have ubiquitin-specific peptidase activity (PubMed:18728397). {ECO:0000269|PubMed:11350945, ECO:0000269|PubMed:18728397, ECO:0000269|PubMed:26912367}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.558
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.59
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |