PSMB3

Chr 17

proteasome 20S subunit beta 3

Also known as: HC10-II

NCBI Gene: 5691ENSG00000277791UniProt: P49720

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 proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. The 26 S proteasome may be involved in trinucleotide repeat expansion, a phenomenon which is associated with many hereditary neurological diseases. Pseudogenes have been identified on chromosomes 2 and 12. Alternative splicing results in multiple transcript variants [provided by RefSeq, Sep 2013]

0
Active trials
7
Pathogenic / LP
33
ClinVar variants
3
Pubs (1 yr)
1.5
Missense Z
0.30
LOEUF· LoF intolerant
Clinical Summary— PSMB3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 22 VUS of 33 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.
0.30LOEUF
pLI 0.957
Z-score 2.90
OE 0.00 (0.00–0.30)
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.
1.51Z-score
OE missense 0.63 (0.53–0.76)
83 obs / 131.6 exp
Tolerant

Mild missense constraint

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.0.00 (0.00–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.53–0.76)
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.1.13
0≤1.21.6
LoF obs/exp: 0 / 9.8Missense obs/exp: 83 / 131.6Syn Z: -0.74

ClinVar Variant Classifications

33 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
VUS22
Likely Benign4
7
Pathogenic
22
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
19
3
0
22
Likely Benign
0
0
2
2
4
Benign
0
0
0
0
0
Total01912233

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

View in ClinVar →

Protein Context — Lollipop Plot

PSMB3 · 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 Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Silencing Core Spliceosome Sm Gene Expression Induces a Cytotoxic Splicing Switch in the Proteasome Subunit Beta 3 mRNA in Non-Small Cell Lung Cancer Cells.
Blijlevens M et al.·Int J Mol Sci
2020
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
NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression.
Waku T et al.·Mol Cell Biol
2020
Effectiveness of bortezomib and temozolomide for eradication of recurrent human glioblastoma cells, resistant to radiation.
Pak O et al.·Prog Brain Res
2021
Identification of proteomic differences in asthenozoospermic sperm samples.
Martínez-Heredia J et al.·Hum Reprod
2008
The 26S proteasome drives trinucleotide repeat expansions.
Concannon C et al.·Nucleic Acids Res
2013
Mutagenic transgene insertion into a region of high gene density and multiple linkage disruptions on mouse chromosome 11.
Kleiter N et al.·Cytogenet Genome Res
2002Functional
AAV exploits subcellular stress associated with inflammation, endoplasmic reticulum expansion, and misfolded proteins in models of cystic fibrosis.
Johnson JS et al.·PLoS Pathog
2011Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Quantitative proteomics analysis reveals the key proteins related to semen quality in Niangya yaks
Wang Y et al.·Proteome Sci
2023
Machine learning-based identification of potential diagnostic signatures in spinal cord injury.
Wang Z et al.·Spinal Cord
2026
Complexity in radiological morphology predicts worse prognosis and is associated with an increase in proteasome component levels in clear cell renal cell carcinoma
Kobatake K et al.·Front Oncol
2022
The Proteomic Profiling of Circulating Extracellular Vesicles of Western Diet and Chemical-Induced Murine MASH Model
Wang SJ et al.·Kaohsiung J Med Sci
2025Functional
Activation of Nkx2.5 transcriptional program is required for adult myocardial repair
de Sena-Tomás C et al.·Nat Commun
2022
Identification of exosome-related genes in Alzheimer's disease: Evidence from transcriptomic and Mendelian randomization analyses.
Jiang X et al.·J Alzheimers Dis
2025
Transcriptome Analysis Reveals Possible Immunomodulatory Activity Mechanism of Chlorella sp. Exopolysaccharides on RAW264.7 Macrophages
Wu S et al.·Mar Drugs
2021Functional
Regulation of TRIB1 abundance in hepatocyte models in response to proteasome inhibition
Soubeyrand S et al.·Sci Rep
2023Functional
WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease
Zeng F et al.·Biomed Res Int
2021
Top 9 full-text resultsSearch PubTator3 ↗

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