PSME4

Chr 2

proteasome activator subunit 4

Also known as: Blm10, PA200, hBlm10

NCBI Gene: 23198 ENSG00000068878 UniProt: Q14997 OMIM: 607705

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable lysine-acetylated histone binding activity; peptidase activator activity; and proteasome binding activity. Predicted to be involved in DNA repair; proteasomal ubiquitin-independent protein catabolic process; and sperm DNA condensation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· predicted