PSMC3

Chr 11

proteasome 26S subunit, ATPase 3

Also known as: DCIDP, EBNDS, RPT5, TBP1

NCBI Gene: 5702 ENSG00000165916 UniProt: P17980

PSMC3 encodes an ATPase subunit of the 26S proteasome that unfolds ubiquitinated proteins for degradation, maintaining cellular protein homeostasis and participating in cell cycle progression, apoptosis, and DNA damage repair. Mutations cause Ebstein-Bezieau neurodevelopmental syndrome and a syndrome characterized by deafness, cataract, impaired intellectual development, and polyneuropathy, with both autosomal recessive and autosomal dominant inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.34), indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, OMIM, UniProt

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core 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. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase 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 one of the ATPase subunits, a member of the triple-A family of ATPases that have chaperone-like activity. This subunit may compete with PSMC2 for binding to the HIV tat protein to regulate the interaction between the viral protein and the transcription complex. A pseudogene has been identified on chromosome 9. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, cataract, impaired intellectual development, and polyneuropathy

UniProtEbstein-Bezieau neurodevelopmental syndrome

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.34

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

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