PSMA2

Chr 7

proteasome 20S subunit alpha 2

Also known as: HC3, MU, PMSA2, PSC2

NCBI Gene: 5683ENSG00000106588UniProt: P25787

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. [provided by RefSeq, Jul 2008]

36
ClinVar variants
24
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PSMA2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 11 VUS of 36 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.982
Z-score 3.56
OE 0.06 (0.02–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.26Z-score
OE missense 0.43 (0.35–0.54)
54 obs / 125.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.43 (0.35–0.54)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25
0≤1.21.6
LoF obs/exp: 1 / 16.7Missense obs/exp: 54 / 125.1Syn Z: -1.32

ClinVar Variant Classifications

36 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS11
Benign1
23
Pathogenic
1
Likely Pathogenic
11
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
1
0
1
VUS
0
5
6
0
11
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total0530136

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

View in ClinVar →

Protein Context — Lollipop Plot

PSMA2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
UCHL-3 as a potential biomarker of ovarian cancer.
Yang Q et al.·Gynecol Oncol
2024
Screening of prognostic risk microRNAs for acute myeloid leukemia.
Gao HY et al.·Hematology
2018
Diminished expression of the ubiquitin-proteasome system in early treatment-naïve patients with rheumatoid arthritis and concomitant type 2 diabetes may be linked to IL-1 pathway hyper-activity; results from PEAC cohort.
Ruscitti P et al.·Arthritis Res Ther
2024Cohort
Construction of a prognostic risk model for acute myeloid leukemia based on exosomal genes and analysis of immune microenvironment characteristics.
Wang MX et al.·Sci Rep
2025Functional
Development and clinical validation of a seven-gene signature based on tumor stem cell-related genes to predict ovarian cancer prognosis.
Wang G et al.·J Ovarian Res
2024
Evaluation of AAV-mediated delivery of shRNA to target basal-like breast cancer genetic vulnerabilities.
Pinto C et al.·J Biotechnol
2019
A computational approach for the identification of key genes and biological pathways of chronic lung diseases: a systems biology approach.
Rezaeeyan H et al.·BMC Med Genomics
2023
An immune-related exosome signature predicts the prognosis and immunotherapy response in ovarian cancer.
Zhu K et al.·BMC Womens Health
2024
Cytoskeletal Alteration Is an Early Cellular Response in Pulmonary Epithelium Infected with Aspergillus fumigatus Rather than Scedosporium apiospermum.
Kanjanapruthipong T et al.·Microb Ecol
2022
Identification of crucial genes of pediatric inflammatory bowel disease in remission by protein-protein interaction network and module analyses.
Liu D et al.·Minerva Pediatr (Torino)
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools