PSMC1

Chr 14

proteasome 26S subunit, ATPase 1

Also known as: NEDGTH, P26S4, RPT2, S4, p56

NCBI Gene: 5700 ENSG00000100764 UniProt: P62191

PSMC1 encodes an ATPase subunit of the 26S proteasome, a multiprotein complex that degrades ubiquitinated proteins in an ATP-dependent manner to maintain cellular protein homeostasis. Mutations cause Birk-Aharoni syndrome, though the phenotypic spectrum remains incompletely defined. The condition follows autosomal recessive inheritance.

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 which have a chaperone-like activity. This subunit and a 20S core alpha subunit interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. This subunit also interacts with the adenovirus E1A protein and this interaction alters the activity of the proteasome. Finally, this subunit interacts with ataxin-7, suggesting a role for the proteasome in the development of spinocerebellar ataxia type 7, a progressive neurodegenerative disorder. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBirk-Aharoni 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

0.14

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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