PSMB8

Chr 6

proteasome 20S subunit beta 8

Also known as: ALDD, D6S216, D6S216E, JMP, LMP7, NKJO, PRAAS1, PSMB5i

NCBI Gene: 5696 ENSG00000204264 UniProt: P28062

PSMB8 encodes a beta subunit of the immunoproteasome, a specialized form of the proteasome that processes antigens for MHC class I presentation and is induced by interferon gamma. Mutations cause proteasome-associated autoinflammatory syndrome 1, a condition characterized by early-onset chronic inflammation affecting multiple organ systems. The condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure 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. 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 member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 3 (proteasome beta 5 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. Two alternative transcripts encoding two isoforms have been identified; both isoforms are processed to yield the same mature subunit. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtProteasome-associated autoinflammatory syndrome 1

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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