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Genetics Home Reference: your guide to understanding genetic conditions
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NLRP3

Reviewed September 2008

What is the official name of the NLRP3 gene?

The official name of this gene is “NLR family, pyrin domain containing 3.”

NLRP3 is the gene's official symbol. The NLRP3 gene is also known by other names, listed below.

What is the normal function of the NLRP3 gene?

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.

Does the NLRP3 gene share characteristics with other genes?

The NLRP3 gene belongs to a family of genes called NLR (nucleotide-binding domain and leucine rich repeat containing family).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the NLRP3 gene related to health conditions?

familial cold autoinflammatory syndrome - caused by mutations in the NLRP3 gene

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.

Muckle-Wells syndrome - caused by mutations in the NLRP3 gene

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.

neonatal onset multisystem inflammatory disease - caused by mutations in the NLRP3 gene

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.

Where is the NLRP3 gene located?

Cytogenetic Location: 1q44

Molecular Location on chromosome 1: base pairs 247,579,457 to 247,612,409

The NLRP3 gene is located on the long (q) arm of chromosome 1 at position 44.

The NLRP3 gene is located on the long (q) arm of chromosome 1 at position 44.

More precisely, the NLRP3 gene is located from base pair 247,579,457 to base pair 247,612,409 on chromosome 1.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about NLRP3?

You and your healthcare professional may find the following resources about NLRP3 helpful.

  • Educational resources - Information pages
    Immunobiology (fifth edition, 2001): Innate Immunity (http://www.ncbi.nlm.nih.gov/books/NBK10769/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for NLRP3 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=114548%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(NLRP3%5BTIAB%5D)%20OR%20((AII/AVP%5BTIAB%5D)%20OR%20(CIAS1%5BTIAB%5D)%20OR%20(cryopyrin%5BTIAB%5D)%20OR%20(FCAS%5BTIAB%5D)%20OR%20(FCU%5BTIAB%5D)%20OR%20(NALP3%5BTIAB%5D)%20OR%20(PYPAF1%5BTIAB%5D)%20OR%20(PYRIN-containing%20APAF1-like%20protein%201%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20360%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/606416)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_NLRP3.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/114548)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=114548)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=16400)
    • Infevers Mutation Registry (http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=4)

What other names do people use for the NLRP3 gene or gene products?

  • 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
  • nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3
  • PYPAF1
  • PYRIN-containing APAF1-like protein 1

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding NLRP3?

cartilage ; cytoplasm ; domain ; exon ; familial ; fever ; gene ; immune system ; inflammation ; injury ; kidney ; leucine ; neonatal ; nucleotide ; protein ; receptor ; syndrome ; tissue ; uric acid ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/17393462?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18172447?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/114548)
  • Farasat S, Aksentijevich I, Toro JR. Autoinflammatory diseases: clinical and genetic advances. Arch Dermatol. 2008 Mar;144(3):392-402. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18347298?dopt=Abstract)
  • Infevers Mutation Registry (http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=4)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16407890?dopt=Abstract)
  • OMIM: NLR FAMILY, PYRIN DOMAIN-CONTAINING 3 (http://omim.org/entry/606416)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16546100?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15300846?dopt=Abstract)
  • Tunca M, Ozdogan H. Molecular and genetic characteristics of hereditary autoinflammatory diseases. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):77-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15720239?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2008
Published: May 13, 2013