PSME4
Chr 2proteasome activator subunit 4
Also known as: Blm10, PA200, hBlm10
This protein recognizes acetylated histones and activates the proteasome to promote ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein disruption.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
269 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 9 | 0 | 9 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 196 | 1 | 0 | 197 |
Likely Benign | 0 | 2 | 3 | 5 | 10 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 198 | 15 | 5 | 218 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PSME4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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