PSMD12

Chr 17

proteasome 26S subunit, non-ATPase 12

Also known as: Rpn5, STISS, p55

NCBI Gene: 5718 ENSG00000197170 UniProt: O00232

This protein is a non-ATPase subunit of the 26S proteasome's 19S regulator that cleaves peptides through ATP/ubiquitin-dependent degradation. Heterozygous loss-of-function mutations cause Stankiewicz-Isidor syndrome through an autosomal dominant inheritance pattern. The high pLI score (0.999) and low LOEUF score (0.162) indicate the gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the likely pathogenic mechanism.

ResearchSummary from RefSeq, OMIM

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 a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtStankiewicz-Isidor syndrome

Clinical highlights

Gene-disease validity (ClinGen)

Stankiewicz-Isidor syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.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

0.16

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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