NLRP3 Identifiers Aliases , AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1, FCAS, FCAS1, FCU, MWS, NALP3, PYPAF1, NLR family, pyrin domain containing 3, NLR family pyrin domain containing 3, DFNA34, KEFH NLRP3 External IDs OMIM: 606416 MGI: 2653833 HomoloGene: 3600 GeneCards: NLRP3 Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 1: 247.42 – 247.45 Mb Chr 11: 59.54 – 59.57 Mb PubMed search   Wikidata NACHT, LRR and PYD domains-containing protein 3 (NALP3), also known as cryopyrin, is a protein that in humans is encoded by the NLRP3 gene located on the long arm of  chromosome 1.
NALP3 is expressed predominantly in
macrophages and as a component of the inflammasome,   : detects products of damaged cells such as extracellular 436 ATP and crystalline uric acid. Activated NALP3 in turn triggers an immune response. Mutations in the NLRP3 gene are associated with a number of organ specific autoimmune diseases.
Nomenclature [ edit ]
NACHT, LRR, and PYD are respectively acronyms for:
NACHT – NAIP (neuronal apoptosis inhibitor protein), C2TA [class 2 transcription activator, of the MHC, HET-E ( heterokaryon incompatibility) and TP1 (telomerase-associated protein 1)
LRR – " leucine- rich repeat"  and is synonymous with NLR, for  or nucleotide-binding domain, leucine-rich repeat"  PYD – " PYRIN domain," after the pyrin proteins The  NLRP3 gene name abbreviates "NLR family, pyrin domain containing 3," where NLR refers to "nucleotide-binding domain, leucine-rich repeat." 
The NACHT, LRR and PYD domains-containing protein 3 is also called:
cold induced autoinflammatory syndrome 1 (CIAS1),
caterpiller-like receptor 1.1 (CLR1.1), and
PYRIN-containing APAF1-like protein 1 (PYPAF1). 
Structure [ edit ]
This gene encodes a pyrin-like protein which contains a
pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with pyrin domain (PYD) of apoptosis-associated speck-like protein containing a CARD (ASC). Proteins which contain the caspase recruitment domain, CARD, have been shown to be involved in inflammation and immune response.
Function [ edit ]
NALP3 is a component of the
innate immune system that functions as a pathogen recognition receptor (PRR) that recognizes pathogen-associated molecular patterns (PAMPs). NALP3 belongs to the  NOD-like receptor (NLR) subfamily of PRRs and NALP3 together with the adaptor ASC protein PYCARD forms a caspase-1 activating complex known as the NALP3 inflammasome. NALP3 in the absence of activating signal is kept in an inactive state complexed with HSP90 and SGT1 in the cytoplasm. NALP3 inflammasome detects danger signals such as crystalline uric acid and extracellular ATP released by damaged cells. These signals release HSP90 and SGT1 from and recruit ASC protein and caspase-1 to the inflammasome complex. Caspase-1 within the activated NALP3 inflammasome complex in turn activates the inflammatory cytokine, IL-1β.
The NALP3 inflammasome appears to be activated by changes in intracellular potassium caused by potassium efflux from
mechanosensitive ion channels located in the cell membrane. It appears that NALP3 is also regulated by  reactive oxygen species (ROS), though the precise mechanisms of such regulation has not been determined.
Pathology [ edit ]
Mutations in the NLRP3 gene have been associated with a spectrum of dominantly inherited
autoinflammatory diseases called cryopyrin-associated periodic syndrome (CAPS). This includes familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS), chronic infantile neurological cutaneous and articular ( CINCA) syndrome, neonatal onset multisystem inflammatory disease (NOMID), and keratoendotheliitis fugax hereditaria. 
Defects in this gene have also been linked to
familial Mediterranean fever. In addition, the NALP3 inflammasome has a role in the  pathogenesis of gout and  neuroinflammation occurring in protein-misfolding diseases, such as Alzheimer's, Parkinson's, and prion diseases.   Amelioration of mouse models of many diseases has been shown to occur by deletion of the NLRP3 inflammasome, including  gout, type 2 diabetes, multiple sclerosis, Alzheimer's disease, and atherosclerosis. The ketone  β-Hydroxybutyrate has been shown to block NLRP3 activation, and thus may be of benefit for many of these diseases.
Deregulation of NALP3 has been connected with
carcinogenesis. For example, all the components of the NALP3 inflammasome are downregulated or completely lost in human hepatocellular carcinoma.
References and notes [ edit ]
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GRCh38: Ensembl release 89: ENSG00000162711 - Ensembl, May 2017
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GRCm38: Ensembl release 89: ENSMUSG00000032691 - Ensembl, May 2017
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"Mouse PubMed Reference:".
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