NLRP3 gene
NLR family pyrin domain containing 3
The NLRP3 gene (also known as CIAS1) provides instructions for making a protein called cryopyrin. Cryopyrin is a member of a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins, which are found in the fluid inside cells (cytoplasm). Cryopyrin is found mainly in white blood cells and in cartilage-forming cells (chondrocytes).
NLR proteins are involved in the immune system, helping to start and regulate the immune system's response to injury, toxins, or invasion by microorganisms. These proteins recognize specific molecules, become activated, and respond by helping to engage components of the immune system. Cryopyrin recognizes bacterial particles; chemicals such as asbestos, silica, and uric acid crystals; and compounds released by injured cells.
Once activated, groups of cryopyrin molecules assemble themselves along with other proteins into structures called inflammasomes, which are involved in the process of inflammation. Inflammation occurs when the immune system sends signaling molecules as well as white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair.
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Several mutations in the NLRP3 gene have been identified in people with familial cold autoinflammatory syndrome. These mutations are in a region of the gene known as exon 3. Researchers believe that the mutations cause cryopyrin to be hyperactive, leading to episodes of fever and inflammation that are usually triggered by exposure to cold.
At least 10 mutations in exon 3 of the NLRP3 gene have been identified in people with Muckle-Wells syndrome. These mutations are believed to cause hyperactive cryopyrin, resulting in episodes of fever and inflammation, as well as the hearing loss and kidney problems that occur in Muckle-Wells syndrome.
About 30 mutations in the NLRP3 gene have been identified in people with neonatal onset multisystem inflammatory disease (NOMID). Almost all of these mutations are found in exon 3. The mutations likely cause cryopyrin to be hyperactive, leading to an inappropriate inflammatory response that results in episodes of fever and widespread inflammatory damage to the body's cells and tissues. It is unclear why some mutations in exon 3 cause the severe symptoms of NOMID, some cause the less serious familial cold autoinflammatory syndrome, and others cause Muckle-Wells syndrome, which is intermediate in severity.
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Cytogenetic Location: 1q44, which is the long (q) arm of chromosome 1 at position 44
Molecular Location: base pairs 247,416,156 to 247,449,108 on chromosome 1 (Homo sapiens Updated Annotation Release 109.20191205, GRCh38.p13) (NCBI)
Related Information
- AGTAVPRL
- AII
- AII/AVP
- AII/AVP receptor-like
- angiotensin/vasopressin receptor AII/AVP-like
- AVP
- C1orf7
- CIAS1
- CLR1.1
- cryopyrin
- FCAS
- FCU
- FLJ95925
- MWS
- NACHT domain-, leucine-rich repeat-, and PYD-containing protein 3
- NACHT, LRR and PYD containing protein 3
- NALP3
- NALP3_HUMAN
- NLR family, pyrin domain containing 3
- nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3
- PYPAF1
- PYRIN-containing APAF1-like protein 1
Related Information
- Aksentijevich I, D Putnam C, Remmers EF, Mueller JL, Le J, Kolodner RD, Moak Z, Chuang M, Austin F, Goldbach-Mansky R, Hoffman HM, Kastner DL. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum. 2007 Apr;56(4):1273-85.
- Church LD, Cook GP, McDermott MF. Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol. 2008 Jan;4(1):34-42. doi: 10.1038/ncprheum0681. Review.
- Farasat S, Aksentijevich I, Toro JR. Autoinflammatory diseases: clinical and genetic advances. Arch Dermatol. 2008 Mar;144(3):392-402. Review.
- Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K, Roose-Girma M, Lee WP, Weinrauch Y, Monack DM, Dixit VM. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006 Mar 9;440(7081):228-32. Epub 2006 Jan 11.
- OMIM: NLR FAMILY, PYRIN DOMAIN-CONTAINING 3
- Sutterwala FS, Ogura Y, Szczepanik M, Lara-Tejero M, Lichtenberger GS, Grant EP, Bertin J, Coyle AJ, Galán JE, Askenase PW, Flavell RA. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity. 2006 Mar;24(3):317-27.
- Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C, Shoham N, Aganna E, Hugot JP, Wise C, Waterham H, Pugnere D, Demaille J, Sarrauste de Menthiere C. Infevers: an evolving mutation database for auto-inflammatory syndromes. Hum Mutat. 2004 Sep;24(3):194-8.
- Tunca M, Ozdogan H. Molecular and genetic characteristics of hereditary autoinflammatory diseases. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):77-80. Review.