USP9Y: Ubiquitin Specific Peptidase 9 Y-Linked
A Y-chromosome gene encoding a deubiquitinating enzyme involved in spermatogenesis and male fertility.
Gene Information Card
| Symbol | USP9Y |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 9 Y-Linked |
| Gene Type | Protein coding |
| Chromosomal Location | Yq11.221 |
| NCBI Gene ID | 8287 ncbi.nlm.nih.gov/gene/8287 |
| Ensembl ID | ENSG00000114374 |
| UniProt ID | O00507 |
| OMIM ID | 400005 |
| HGNC ID | 12633 |
| Aliases | DFFRY, SPGFY1 |
Description
USP9Y (Ubiquitin Specific Peptidase 9 Y-Linked) is a protein-coding gene located on the Y chromosome at Yq11.221. It encodes a deubiquitinating enzyme that removes ubiquitin from target proteins, regulating protein stability and signaling. USP9Y is predominantly expressed in the testis and is essential for normal spermatogenesis. Deletions or mutations in USP9Y are a known cause of azoospermia factor a (AZFa) region-related male infertility, specifically non-obstructive azoospermia and severe oligozoospermia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (non-obstructive azoospermia) | Deletion or mutation of USP9Y disrupts deubiquitination of key spermatogenic proteins, leading to impaired germ cell development and maturation. | ClinVar, OMIM |
| Spermatogenic failure Y-linked type 1 (SPGFY1) | Loss-of-function variants in USP9Y cause spermatogenic arrest at the spermatocyte stage, resulting in azoospermia. | OMIM #400005 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Prostate | 1.2 | Low |
| Skin | 0.8 | Low |
| Brain | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatogonia | 42.1 | High expression in germ cells |
| Sertoli cells | 5.3 | Moderate |
| Leydig cells | 2.1 | Low |
| HEK293 | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1276C>T (p.Arg426*) | Nonsense | Rare | Loss of function; truncation of deubiquitinase domain |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein expression |
| Whole gene deletion | Deletion | ~1-2% in infertile men | AZFa microdeletion; causes azoospermia |
Mutation functional classification
Loss of Function (LOF)
USP9Y loss-of-function mutations (nonsense, frameshift, deletions) impair deubiquitinating activity, leading to accumulation of ubiquitinated substrates and disruption of spermatogenesis.
Gain of Function (GOF)
No gain-of-function mutations reported for USP9Y.
Dominant Negative (DN)
No dominant-negative mutations reported for USP9Y.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type deubiquitinase activity | • ubiquitin-specific protease activity |
| • proteolysis | • protein deubiquitination |
| • spermatogenesis | • male gonad development |
Pathways
• Ubiquitin-proteasome system
• Spermatogenesis
Protein Summary
USP9Y encodes a 2555-amino acid deubiquitinating enzyme (DUB) belonging to the ubiquitin-specific protease (USP) family. The protein contains a catalytic domain with cysteine-type peptidase activity that cleaves ubiquitin from target proteins, thereby regulating protein turnover, localization, and function. USP9Y is highly expressed in testicular germ cells and is required for meiotic progression during spermatogenesis. Its absence leads to spermatogenic arrest and male infertility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP9Y Knockout HEK293 Cell Line | EDJ-KQ6196 | Human | 8287 | Details Get a Quote |
| USP9Y Knockout A-549 Cell Line | EDJ-KQ30031 | Human | 8287 | Details Get a Quote |
| USP9Y Knockout HCT 116 Cell Line | EDJ-KQ28726 | Human | 8287 | Details Get a Quote |
| USP9Y Knockout HeLa Cell Line | EDJ-KQ54844 | Human | 8287 | Details Get a Quote |
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