USP9Y
protein-codingubiquitin specific peptidase 9 Y-linked, the group of Armadillo like helical domain containing|Minor histocompatibility antigens|Ubiquitin specific peptidases
Gene summary
This gene is a member of the peptidase C19 family. It encodes a protein that is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. [provided by RefSeq, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~323.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Genitourinary
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to USP9Y variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004654.4. 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 | 27 | 4 | 1 | 32 | ||
| missense | 105 | 4 | 1 | 110 | ||
| nonsense | 10 | 10 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 12 | 12 | ||||
| Total | 1 | 0 | 156 | 8 | 2 | 167 |
Highest pathogenic variant AF is 0.000026674965
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004645.2 | 44 | MANE Select | |
| Ensembl | ENSP00000342812.3 | 44 | MANE Select | |
| Ensembl | ENSP00000406876.1 | 5 | Standard | |
| Ensembl | ENSP00000498372.1 | 44 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- ubiquitin-dependent protein catabolic process
- transforming growth factor beta receptor signaling pathway
- spermatogenesis
- protein deubiquitination
- BMP signaling pathway
Molecular Function
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- cysteine-type peptidase activity
- co-SMAD binding
Cellular Component
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338981
- Coding exons
- 44
- Length
- 159605
- Individuals with no LoFs
- 67925
- Homozygous LoFs
- 25
- Heterozygous LoFs
- 0
- Defined
- 67950
- p
- 0.000184
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.391 | 409 | 387 | 1.06 | 0.0000595 | 16977 |
| Missense (PolyPhen) | 129 | 131.11 | 0.98388 | 5686 | ||
| Synonymous | -1.35 | 148 | 129 | 1.15 | 0.0000193 | 4700 |
| Loss of Function | 3.52 | 14 | 37.2 | 0.377 | 0.00000626 | 1628 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.00065 | notable |
| Latino/Admixed American | 0.00042 | 0.00021 | rare |
| Ashkenazi Jewish | 0.0012 | 0.00058 | notable |
| East Asian | 0.00044 | 0.00022 | rare |
| Finnish | 0.00018 | 0.000089 | rare |
| European (Non-Finnish) | 0.00029 | 0.00014 | rare |
| South Asian | 0.00019 | 0.000087 | rare |
| Other | 0.00067 | 0.00031 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May function as a ubiquitin-protein or polyubiquitin hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin. Essential component of TGF-beta/BMP signaling cascade. Deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33. Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiquitination of SMAD4 by USP9X re-empowers its competence to mediate TGF-beta signaling (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Spermatogenic failure Y-linked 2 (SPGFY2) [MIM:415000]: A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility. {ECO:0000269|PubMed:10581029}. Note=The disease may be caused by mutations affecting the gene represented in this entry. The role of USP9Y in spermatogenesis failure is uncertain (PubMed:19246359). A 4-bp deletion in a splice-donor site, causing exon skipping and protein truncation has been observed in non- obstructive azoospermia (PubMed:10581029). However, complete USP9Y deletion has been detected in individuals with no spermatogenic defects (PubMed:19246359). {ECO:0000269|PubMed:10581029, ECO:0000269|PubMed:19246359}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.167
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |