Gene: NLRP3

Alternate names for this Gene: AGTAVPRL|AII|AVP|C1orf7|CIAS1|CLR1.1|DFNA34|FCAS|FCAS1|FCU|KEFH|MWS|NALP3|PYPAF1

Gene Summary: This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NALP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. Mutations in this gene are associated with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, and neonatal-onset multisystem inflammatory disease (NOMID). Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Alternative 5' UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5' UTR splice patterns are biologically valid.

Gene is located in Chromosome: 1

Location in Chromosome : 1q44

Description of this Gene: NLR family pyrin domain containing 3

Type of Gene: protein-coding

rs12239046 in NLRP3 gene and Blood basophil count (lab test) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs12239046 in NLRP3 gene and C-reactive protein measurement PMID 21300955 2011 Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.

PMID 30388399 2018 Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

rs121908152 in NLRP3 gene and Chronic Infantile Neurological, Cutaneous, and Articular Syndrome PMID 12483741 2002 De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.

PMID 15334500 2004 Variant chronic infantile neurologic, cutaneous, articular syndrome due to a mutation within the leucine-rich repeat domain of CIAS1.

PMID 14630794 2004 Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU.

PMID 24952504 2014 The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.

PMID 15593220 2004 Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.

PMID 15231984 2004 A novel CIAS1 mutation and plasma/cerebrospinal fluid cytokine profile in a German patient with neonatal-onset multisystem inflammatory disease responsive to methotrexate therapy.

PMID 12032915 2002 Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes.

rs121908146 in NLRP3 gene and Cryopyrin-Associated Periodic Syndromes PMID 26245507 2015 Musculoskeletal symptoms in patients with cryopyrin-associated periodic syndromes: a large database study.

PMID 15801036 2005 Intrafamilial variable phenotypic expression of a CIAS1 mutation: from Muckle-Wells to chronic infantile neurological cutaneous and articular syndrome.

PMID 11687797 2001 Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.

PMID 26931528 2016 Neurology of the cryopyrin-associated periodic fever syndrome.

PMID 27134254 2016 NLRP3 A439V Mutation in a Large Family with Cryopyrin-associated Periodic Syndrome: Description of Ophthalmologic Symptoms in Correlation with Other Organ Symptoms.

PMID 25596455 2015 A functional inflammasome activation assay differentiates patients with pathogenic NLRP3 mutations and symptomatic patients with low penetrance variants.

PMID 22193915 2012 Characterization of NLRP3 variants in Japanese cryopyrin-associated periodic syndrome patients.

PMID 15020601 2004 Cryopyrin-induced interleukin 1beta secretion in monocytic cells: enhanced activity of disease-associated mutants and requirement for ASC.

PMID 11992256 2002 New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.

PMID 24517500 2014 CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in cryopyrin-associated periodic syndromes escapes the restriction.

PMID 20472245 2010 Follow-up and quality of life of patients with cryopyrin-associated periodic syndromes treated with Anakinra.

PMID 16100350 2005 The T348M mutated form of cryopyrin is associated with defective lipopolysaccharide-induced interleukin 10 production in CINCA syndrome.

PMID 21356079 2011 Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS).

PMID 17178739 2007 A cryopyrin-associated periodic syndrome with joint destruction.

PMID 25730877 2015 Cell stress increases ATP release in NLRP3 inflammasome-mediated autoinflammatory diseases, resulting in cytokine imbalance.

PMID 26531310 2015 Early detection of sensorineural hearing loss in Muckle-Wells-syndrome.

PMID 23442610 2013 The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age.

PMID 16081838 2005 IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients.

PMID 12522564 2003 Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P.

rs1553293095 in NLRP3 gene and DEAFNESS, AUTOSOMAL DOMINANT 34, WITH OR WITHOUT INFLAMMATION PMID 28847925 2017 NLRP3 mutation and cochlear autoinflammation cause syndromic and nonsyndromic hearing loss DFNA34 responsive to anakinra therapy.

rs12239046 in NLRP3 gene and Eosinophil count procedure PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs121908146 in NLRP3 gene and Familial Cold Autoinflammatory Syndrome 1 PMID 12355493 2002 Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis.

PMID 15593220 2004 Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.

PMID 12522564 2003 Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P.

PMID 11687797 2001 Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.

PMID 17284928 2007 A novel missense mutation in CIAS1 encoding the pyrin-like protein, cryopyrin, causes familial cold autoinflammatory syndrome in a family of Ethiopian origin.

PMID 11992256 2002 New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.

PMID 24952504 2014 The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.

rs10157379 in NLRP3 gene and Fibrinogen assay PMID 23969696 2013 Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

PMID 26561523 2016 A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

PMID 20978265 2011 Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe).

PMID 28107422 2017 Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.

PMID 20031576 2009 Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.

rs10157379 in NLRP3 gene and Fibrinogen, CTCAE PMID 23969696 2013 Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

PMID 20978265 2011 Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe).

PMID 20031576 2009 Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.

rs12143966 in NLRP3 gene and Finding of Mean Corpuscular Hemoglobin PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs12239046 in NLRP3 gene and Granulocyte count PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs200154873 in NLRP3 gene and Keratitis Fugax Hereditaria PMID 29366613 2018 Keratoendotheliitis fugax hereditaria is an autoinflammatory cryopyrin-associated periodic syndrome caused by a missense mutation c.61G>C in exon 1 of NLRP3 in Finnish patients.

rs121908147 in NLRP3 gene and Muckle-Wells Syndrome PMID 11992256 2002 New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.

PMID 12355493 2002 The V200M variant was present in all affected members of the British family with MWS, in 2 of the 50 subjects with uncharacterized periodic fevers, and in 1 of 130 Caucasian and 2 of 48 Indian healthy controls.

PMID 15593220 2004 Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.

PMID 11687797 2001 Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.

PMID 24952504 2014 The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.

PMID 12355493 2002 Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis.

PMID 12355493 2002 The R262W variant was also present in the subject with sporadic MWS.

PMID 11992256 2002 The R260W mutation was identified in two families with MWS and in two families with FCU, of different ethnic origins, thereby demonstrating that a single CIAS1 mutation may cause both syndromes.

rs12239046 in NLRP3 gene and Neutrophil count (procedure) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs144084486 in NLRP3 gene and Platelet Count measurement PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs12239046 in NLRP3 gene and White Blood Cell Count procedure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs10157379 in NLRP3 gene and fibrinogen activity PMID 23969696 2013 Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

PMID 20978265 2011 Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe).

PMID 20031576 2009 Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.