Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NLRP3 contributors: mct/shn - updated : 22-09-2018
HGNC name NLR family, pyrin domain containing 3
HGNC id 16400
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal CARD or pyrin domains needed for homotypic protein-protein interaction
  • a nucleotide binding site (NBS, NACHT subfamily)
  • a leucine rich repeat region (LRR)
  • HOMOLOGY
    interspecies ortholog to Nlrp3, Mus musculus
    ortholog to Nlrp3, Rattus norvegicus
    ortholog to NLRP3, Pan troglodytes
    Homologene
    FAMILY
  • PYD/CARD-containing family of apoptosis regulators and activators of pro-inflammatory caspases
  • NALP subfamily of the CATERPILLER protein family
  • NLRP family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • a potential inducer of apoptosis
  • a key regulator of inflammation, induced to dampen NF-kappaB-dependent proinflammatory signals
  • may play an important role in the development of hypertension, based on inflammation brought on by NFKB activation
  • implicated in the activation of caspase-1 by the Toll-like receptors (TLRs) during the cells response to microbial infection
  • role of the NLRP3 inflammasome in regulating glucose homeostasis
  • controls the inflammasome, a crucial molecular platform that regulates activation of caspase-1 and processing of interleukin (IL)-1beta—two key mediators of inflammation
  • play important roles in both mammalian innate immune system and reproductive system
  • possible involvement of NLRP3-inflammasome in the activation of caspase-1 consequent to geranylgeranyl pyrophosphate decrement
  • redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella
  • NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases (
  • NLRP3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance
  • NLRP3 inflammasome activation in obesity promotes macrophage-mediated T cell activation in adipose tissue and impairs insulin sensitivity
  • signaling by innate immune receptors such as TLR4 and NLRP3 regulate metabolism
  • important activating component of the inflammasome, is involved in neointima formation after vascular injury
  • plays a non-redundant role in vascular damage mediated neointima formation
  • mediates the pathological effect of hydroxyapatite (HA) crystals, suggesting a critical role for the inflammasome in the pathogenesis of osteoarthritis
  • NLRP3 inflammasome plays a pivotal role in the development of HA deposition diseases of joints
  • glucocorticoid-responsive gene in cultured and primary macrophages
  • ability of glucocorticoids to sensitize the NLRP3 inflammasome to ATP could also play a role in enhancing IL1B release during sterile inflammation
  • intracellular receptors, such as NLRP1, NLRP3, NLRP6 and NLRC4, which mediate the assembly of inflammasome complexes leading to the activation of procaspase-1
  • critical role for Ca2+ signaling in activation of the NLRP3 inflammasome
  • Ca2+ and cAMP are two key molecular regulators of the NLRP3 inflammasome that have critical roles in the molecular pathogenesis of cryopyrin-associated periodic syndromes (CAPS)
  • is an important pattern recognition receptor involved in mediating inflammasome activation in response to viral and bacterial infections as well as various proinflammatory stimuli associated with tissue damage or malfunction
  • fundamental role for NLRP3/CASP1 mediated inflammation in behavioural and cognitive dysfunction in Alzheimer disease
  • involvement of the NLRP3 inflammasome in DNA damage responses induced by cellular stress
  • is an upstream target that controls age-related inflammation
  • is involved in the early stages of the inflammatory response by sensing cellular damage or distress due to viral or bacterial infection
  • roles of mitochondria in NLRP3 inflammasome activation
  • regulates chemokine-mediated functions and recruitment of neutrophils, and thereby contributes to hepatic I/R injury independently of inflammasomes
  • NLRC4 and NLRP3, which normally form distinct inflammasomes, activate an lysophosphatidylcholine (LPC)-induced inflammasome and are important in astrogliosis and microgliosis
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ASC (
  • ASC, CARD-containing protein Cardinal, and caspase-1
  • nucleotide-binding oligomerization domain containing 2, NOD2
  • PYCARD connects pathogen/danger sensors such as NLRP3 and NLRC4 with caspases and is involved in inflammation and cell death
  • CASP1 interacting with PYCARD, AIM2 and NLRP3 (PYCARD inflammasomes, including AIM2 and NLRP3, are critical for CASP1 activation induced by S. pneumoniae)
  • GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents
  • endogenous non-coding RNA-induced NLRP3 inflammasome activation results from DICER1 deficiency in a non-immune cell
  • DDIT3, a protein known to regulate Ca2+ release from the ER during ER stress, amplifies NLRP3 inflammasome activation
  • Ca2+ signaling critically regulates NLRP3 inflammasome activation by triggering mitochondrial damage
  • EIF2AK2 physically interacts with multiple inflammasome components, including NLR family pyrin domain-containing 3 (NLRP3)
  • PYCARD interacts with NLRP3 via a homotypic PYD interaction and recruits procaspase-1 via a homotypic caspase recruitment domain interaction
  • is a key component of one of several distinct cytoplasmic multiprotein complexes (inflammasomes) that mediate the maturation of the proinflammatory cytokine IL1B by activating CASP1
  • recognition of extracellular Ca2+ through CASR activates the NLRP3 inflammasome
  • BRCC3, is a critical regulator of NLRP3 activity by promoting its deubiquitination
  • TRPM2 is a key factor that links oxidative stress to the NLRP3 inflammasome activation
  • DHX33 is a cytosolic RNA sensor that activates the NLRP3 inflammasome
  • mitochondria play a critical role in the activation of the NLRP3 inflammasome through the direct binding of NLRP3 to cardiolipin
  • ATG7-induced CTSB overexpression contributes to an NLRP3-dependent proinflammatory response and subsequently impairs glucose-stimulated insulin secretion (GSIS) independently of apoptosis
  • MAVS facilitates the recruitment of NLRP3 to the mitochondria and may enhance its oligomerization and activation by bringing it in close proximity to mitochondrial reactive oxygen species
  • MFN2 is required for the full activation of the NLRP3 inflammasomes in macrophages
  • NLRP3 inflammasome activates CASP1, which cleaves pro–IL1B to mature forms and stimulates their secretion
  • lactate negatively regulates TLR induction of the NLRP3 inflammasome and production of IL1B, via ARRB2 and HCAR1
  • ubiquitination of DHX33 by TRIM33 is lysine 63 specific and is required for the formation of the DHX33-NLRP3 inflammasome complex
  • is a transcriptional target of NR1I2 (NR1I2 regulates innate immunity via activation of NLRP3 inflammasome in vascular endothelial cells)
  • ARRB1 plays a critical role in the assembly and activation of two major canonical inflammasomes, NLRC4, NLRP3
  • BTK physically interacts with PYCARD and NLRP3
  • CASP4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells
  • PLIN2 inhibits insulin&
  • 8209;induced glucose uptake by activating NLRP3, CASP1 and IL1B, leading to a decreased IRS1 expression
  • TRIM31 is a feedback suppressor of NLRP3 inflammasome
  • bile acids and NR1H4 play pivotal roles in sepsis via controlling the NLRP3 inflammasome
  • endogenous NLRC3 interacts with both PYCARD and pro-caspase-1 but not with NLRP3, disrupts PYCARD speck formation through its CARD, and impairs the PYCARD and pro-caspase-1 interaction
  • CXCL1 and CXCL2 regulate NLRP3 inflammasome activation via G-Protein-Coupled Receptor CXCR2
  • MAP3K5, MAP3K6 was required for NLRP3 up-regulation after lipopolysaccharide treatment in primary bone marrow-derived macrophages and lung fibroblasts as well as during infection with Burkholderia thailandensis and influenza virus
  • HSPD1 further activates NLRP3 inflammasome by elevating NLRP3 expression both at RNA and protein levels
  • cell & other
    REGULATION
    activated by by elevated levels of glucose, cholesterol crystals, and amyloid beta
    inhibited by recruited by ASC to distinct cytoplasmic loci and inducing NF-kappa B activation and caspase 1 cytokine processing
    Other is rapidly and directly regulated by glucocorticoids
    activation of the NLRP3 inflammasome requires Ca2+ signaling
    ASSOCIATED DISORDERS
    corresponding disease(s) FCU , MWS , CINCA , DFNA34
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in autoinflammatory disease
    constitutional     --over  
    higher in MVK patients higher than in untreated healthy controls
    constitutional       gain of function
    in age-related macular degeneration (AMD)
    constitutional germinal mutation      
    in NLRP3 in ischemic heart tissues but not in non-ischemic control tissue
    constitutional       loss of function
    deficiency leads to decreased APP levels and deposition
    constitutional       gain of function
    activation of the NLRP1 and NLRP3 inflammasomes in Alzheimer disease
    Susceptibility
  • to essential hypertension
  • to autoinflammatory disease and to psoriatic juvenile idiopathic arthritis
  • to Crohn disease
  • Variant & Polymorphism SNP , insertion/deletion
  • homozygote of 12 repeat allele VNTR was significantly higher in patients with hypertension
  • SNP increasing the risk of Crohn disease
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    could open new avenues to therapeutic intervention
    miscelleaneoussenescence 
    innovative therapeutic strategy to lower NLRP3 activity to delay multiple age-related chronic diseases
    neurosensorialvisualdegenerative
    therapeutic inhibition of both VEGFA and IL1B or the NLRP3 inflammasome is therefore likely to suppress both forms of AMD
    neurologyneurodegenerativealzheimer
    NLRP3 inflammasome inhibition represents a novel therapeutic intervention for AD
    ANIMAL & CELL MODELS
  • Nlrp3(-/-) mice displa high susceptiblity of infection with a pathogenic influenza A virus (
  • mice carrying a mutation in the Nlrp3 gene produce massive amounts of IL-1beta upon stimulation with microbial stimuli, skin inflammation characterized by neutrophil infiltration and a Th17 cytokine-dominant response (
  • Nlrp3(-/-) mice exhibited delayed neuroinflammation, demyelination, and oligodendrocyte loss
  • ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling
  • mice lacking Nlrp3 or caspase-1 showed decreased joint pathology in an ank-deficient model of arthritis
  • Nlrp3-/- mice are resistant to the development of Experimental autoimmune encephalomyelitis (EAE), suggesting the association of the NLRP3 inflammasome with EAE development