PSMA8: Proteasome 20S Subunit Alpha 8
A testis-specific proteasome subunit essential for spermatogenesis and linked to male infertility
Gene Information Card
| Symbol | PSMA8 |
|---|---|
| Full Name | Proteasome 20S Subunit Alpha 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 18q11.2 |
| NCBI Gene ID | 143471 ncbi.nlm.nih.gov/gene/143471 |
| Ensembl ID | ENSG00000141480 |
| UniProt ID | Q8TC59 |
| OMIM ID | 610449 |
| HGNC ID | 22919 |
| Aliases | PSMA7L, MGC138290, proteasome subunit alpha 7-like |
Description
PSMA8 encodes a member of the peptidase T1A family, specifically an alpha subunit of the 20S core proteasome complex. This subunit is testis-enriched and replaces the canonical PSMA7 subunit in spermatogenic cells. It is essential for the assembly and catalytic activity of the testis-specific proteasome, which degrades ubiquitinated proteins during spermatogenesis. Loss-of-function mutations in PSMA8 lead to impaired proteasome activity, accumulation of ubiquitinated substrates, and meiotic arrest, resulting in non-obstructive azoospermia and male infertility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spermatogenic failure 8 (SPGF8) | Loss-of-function mutations impair testis-specific proteasome assembly, causing meiotic arrest and defective sperm production. | OMIM #618152; PubMed: 30683845, 31558766 |
| Non-obstructive azoospermia | PSMA8 deficiency leads to proteasome dysfunction and accumulation of ubiquitinated proteins in spermatocytes, blocking spermatid formation. | ClinVar; PubMed: 30683845 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Fallopian tube | 0.8 | Not detected |
| Prostate | 0.6 | Not detected |
| Ovary | 0.5 | Not detected |
| Other tissues | <0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatocytes (primary) | High | Testis-specific expression; essential for meiotic phase |
| Spermatids | Moderate | Post-meiotic expression declines |
| Sertoli cells | Low | Supporting cells; minimal expression |
| HEK293 | 0.1 | Negligible in non-germline cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.329G>A (p.Arg110Gln) | Missense | Rare | Loss of proteasome assembly; causes azoospermia |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; spermatogenic failure |
| c.511C>T (p.Arg171*) | Nonsense | Rare | Truncated protein; meiotic arrest |
| c.637_638del (p.Leu213Valfs*2) | Frameshift | Rare | Loss of function; male infertility |
Mutation functional classification
Loss of Function (LOF)
All reported pathogenic mutations in PSMA8 are loss-of-function, leading to reduced or absent proteasome activity in testis, meiotic arrest, and azoospermia.
Gain of Function (GOF)
No gain-of-function mutations have been described for PSMA8.
Dominant Negative (DN)
No dominant-negative effects reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin-proteasome system (KEGG: hsa03050)
• Proteasome (Reactome: R-HSA-68886)
• Spermatogenesis (Reactome: R-HSA-1500620)
Protein Summary
PSMA8 is a 256-amino-acid alpha subunit of the 20S proteasome, specifically expressed in the testis. It replaces the canonical PSMA7 subunit in spermatogenic cells, forming a specialized proteasome variant (spermatoproteasome) that degrades ubiquitinated proteins during meiosis and spermiogenesis. The protein contains a proteasome alpha-type domain and is essential for male fertility. Loss of PSMA8 function disrupts proteasome assembly, leading to accumulation of ubiquitinated substrates, meiotic arrest, and non-obstructive azoospermia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSMA8 Knockout HEK293 Cell Line | EDJ-KQ10383 | Human | 143471 | Details Get a Quote |
| PSMA8 Knockout HeLa Cell Line | EDJ-KQ58486 | Human | 143471 | Details Get a Quote |
| PSMA8 Knockout A-549 Cell Line | EDJ-KQ66975 | Human | 143471 | Details Get a Quote |
| PSMA8 Knockout HCT 116 Cell Line | EDJ-KQ75374 | Human | 143471 | Details Get a Quote |
