PSMA8

Chr 18

proteasome 20S subunit alpha 8

Also known as: PSMA7L

NCBI Gene: 143471ENSG00000154611UniProt: Q8TAA3

This gene encodes a component of the spermatoproteasome that degrades specific proteins during male meiosis, including histones and meiotic proteins like RAD51 and RPA1, and is essential for proper chromosome pairing during spermatogenesis. While the gene shows low constraint against loss-of-function variants (pLI ~0, LOEUF ~1), no definitive human disease associations have been established based on the provided information. Given its testis-specific expression and role in male meiosis, mutations would likely affect male fertility if pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
36
P/LP submissions
0%
P/LP missense
1.03
LOEUF
DN
Mechanism· predicted
Clinical Summary— PSMA8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 44 VUS of 82 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.49
OE 0.59 (0.35–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.91 (0.79–1.06)
126 obs / 138.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.35–1.03)
0≤0.351.4
Missense OE0.91 (0.79–1.06)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 9 / 15.3Missense obs/exp: 126 / 138.2Syn Z: -0.12
DN
0.76top 25%
GOF
0.4875th %ile
LOF
0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic1
VUS44
Likely Benign1
33
Pathogenic
1
Likely Pathogenic
44
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
1
0
1
VUS
1
36
7
0
44
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total13741079

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PSMA8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients