PSMB4

Chr 1AR

proteasome 20S subunit beta 4

Also known as: HN3, HsN3, PRAAS3, PROS-26, PROS26

PSMB4 encodes a non-catalytic beta subunit of the 20S proteasome core complex, which degrades intracellular proteins to maintain cellular protein homeostasis and generate MHC class I antigenic peptides. Mutations cause proteasome-associated autoinflammatory syndrome 3, an autosomal recessive disorder involving immune system dysfunction. The gene shows relatively low constraint to loss-of-function variants, consistent with recessive inheritance patterns.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.791 OMIM phenotype
Clinical SummaryPSMB4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.003
Z-score 2.18
OE 0.42 (0.240.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.47Z-score
OE missense 0.90 (0.781.03)
142 obs / 158.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.240.79)
00.351.4
Missense OE0.90 (0.781.03)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 7 / 16.6Missense obs/exp: 142 / 158.5Syn Z: 0.12
DN
0.7227th %ile
GOF
0.5464th %ile
LOF
0.3067th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PSMB4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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