NLRP3 inflammasome assembly

A scoped project: ten candidate genes, three already reviewed

AI Gene Review · projects/NLRP3_INFLAMMASOME · 2026

Bottom line

  • NLRP3 recruits PYCARD (ASC) to activate caspase-1, which matures IL-1β and IL-18 and cleaves gasdermin D to open pyroptotic pores.
  • Scoped, not yet started: no project-specific review work has been done.
  • 3 of 10 candidates already reviewed (NLRP3, CASP4, GSDMD; 364 annotations). PYCARD, CASP1 and five others have no gene folder; a draft NLR signaling module already includes NLRP3, PYCARD and CASP1.

The mechanism and what is covered

Why this complex

  • A major therapeutic target; gain-of-function NLRP3 causes CAPS, and inflammasome activity contributes to gout, atherosclerosis and Alzheimer disease.
  • Post-2020 work on the trans-Golgi activation site, post-translational control, assembly structures and the GSDMD pore is likely under-represented in GO.
  • A bounded complex with a clear order: sensor → adaptor → caspase → substrates.

A gap in GO the NLRP3 review found

NLRP3 is activated by unrelated stimuli it does not bind, so GO:0140299 molecular sensor activity does not fit. The review proposes inflammasome sensor activity.

Status and next steps

Gene State
NLRP3 (188 ann.), CASP4 (99), GSDMD (77) Reviewed (COMPLETE)
PYCARD, CASP1, CASP5, IL1B, IL18, NEK7, BRCC3 No gene folder
  • ⬜ just fetch-gene human <GENE> for the seven missing genes, starting with PYCARD and CASP1.
  • ⬜ Extend modules/nlr_signaling.yaml (DRAFT) with the reviewed inflammasome genes.

Read more: projects/NLRP3_INFLAMMASOME.md · modules/nlr_signaling.yaml