PSMB6
Chr 17proteasome 20S subunit beta 6
Also known as: DELTA, LMPY
PSMB6 encodes a beta subunit of the 20S proteasome core complex that degrades intracellular proteins through both ubiquitin-dependent and ubiquitin-independent pathways, displaying peptidylglutamyl-hydrolizing activity within the complex. Mutations cause autosomal recessive proteasome-associated autoinflammatory syndrome with chronic atypical neutrophilic dermatosis, characterized by early-onset recurrent fever, distinctive skin lesions, and systemic inflammation. This gene shows tolerance to loss-of-function variants in the general population, consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
PSMB6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools