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Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 1036 | 1q44 | NLRP3 | NLR family pyrin domain containing 3 | |
Mouse | - | 1033 | 11 B1.3 | Nlrp3 | NLR family, pyrin domain containing 3 | |
Rat | - | - | 10q22 | Nlrp3 | NLR family, pyrin domain containing 3 |
Database Links ![]() |
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CATH/Gene3D | 3.80.10.10 |
ChEMBL Target | CHEMBL1741208 (Hs), CHEMBL3779755 (Mm) |
Ensembl Gene | ENSG00000162711 (Hs), ENSMUSG00000032691 (Mm), ENSRNOG00000003170 (Rn) |
Entrez Gene | 114548 (Hs), 216799 (Mm), 287362 (Rn) |
Human Protein Atlas | ENSG00000162711 (Hs) |
KEGG Gene | hsa:114548 (Hs), mmu:216799 (Mm), rno:287362 (Rn) |
OMIM | 606416 (Hs) |
Pharos | Q96P20 (Hs) |
UniProtKB | Q96P20 (Hs), Q8R4B8 (Mm) |
Wikipedia | NLRP3 (Hs) |
Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis (pyroptosis). Drug-like NLRP3 inhibitors are under investigation as novel therapeutics for the treatment of autoinflammatory diseases and neuroinflammation, as an alternative to anti-IL-1 therapies such as rilonacept, anakinra and canakinumab [1,7]. The potential of pharmacological modulation of the NLRP3 inflammasome as a mechanism to treat inflammatory diseases is reviewed by Mangan et al. (2018) [8]. NLRP3 inflammasome activation by tau in microglia has been demonstrated to drive amyloid-β pathology, including neuroinflammation and formation of neurofibrillary tangles [5]. |
Immuno Process Associations | |||||||||||||||
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Physiological Functions Comments | |
Involved in inflammasome formation and caspase-1 activation. |
Clinically-Relevant Mutations and Pathophysiology ![]() |
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Biologically Significant Variants ![]() |
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1. Baldwin AG, Brough D, Freeman S. (2016) Inhibiting the Inflammasome: A Chemical Perspective. J. Med. Chem., 59 (5): 1691-710. [PMID:26422006]
2. Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A et al.. (2015) A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med., 21 (3): 248-55. [PMID:25686105]
3. Dodé C, Le Dû N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G, Meyrier A, Watts RA, Scott DG, Nicholls A et al.. (2002) New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. Am. J. Hum. Genet., 70 (6): 1498-506. [PMID:11992256]
4. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat. Genet., 29 (3): 301-5. [PMID:11687797]
5. Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, Schwartz S, Albasset S, McManus RM, Tejera D et al.. (2019) NLRP3 inflammasome activation drives tau pathology. Nature, 575 (7784): 669-673. [PMID:31748742]
6. Jiang H, He H, Chen Y, Huang W, Cheng J, Ye J, Wang A, Tao J, Wang C, Liu Q et al.. (2017) Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J. Exp. Med., 214 (11): 3219-3238. [PMID:29021150]
7. Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. (2018) Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov, 17 (9): 688. [PMID:30116046]
8. Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. (2018) Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov, 17 (8): 588-606. [PMID:30026524]
9. Marchetti C, Swartzwelter B, Gamboni F, Neff CP, Richter K, Azam T, Carta S, Tengesdal I, Nemkov T, D'Alessandro A et al.. (2018) OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc. Natl. Acad. Sci. U.S.A., 115 (7): E1530-E1539. [PMID:29378952]