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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 1473 | 17p13 | NLRP1 | NLR family pyrin domain containing 1 | |
| Mouse | - | - | 11 43.21 cM | Nlrp1a | NLR family, pyrin domain containing 1A | |
| Rat | - | - | Nlrp1a | NLR family, pyrin domain containing 1A | ||
| Previous and Unofficial Names |
| CARD7 | CLR17.1 | NAC | NALP1 | NACHT, leucine rich repeat and PYD containing 1 | NLR family, pyrin domain containing 1 | resistant anthrax lethal toxin | DEFCAP | CIDED | DEFCAP-L/S | PP1044 | SLEV1 | VAMAS1 | NLR family |
| Database Links |
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| Alphafold | Q9C000 (Hs) |
| ChEMBL Target | CHEMBL1741214 (Hs) |
| Ensembl Gene | ENSG00000091592 (Hs), ENSMUSG00000069830 (Mm), ENSRNOG00000023143 (Rn) |
| Entrez Gene | 22861 (Hs), 195046 (Mm), 360557 (Rn) |
| Human Protein Atlas | ENSG00000091592 (Hs) |
| KEGG Gene | hsa:22861 (Hs), mmu:195046 (Mm), rno:360557 (Rn) |
| OMIM | 606636 (Hs) |
| Pharos | Q9C000 (Hs) |
| UniProtKB | Q9C000 (Hs) |
| Wikipedia | NLRP1 (Hs) |
| Immunopharmacology Comments |
| NLRP1 is a cytosolic sensor of bacterial infection and regulator of the resulting innate immune response [4]. It initiates formation of a large, signal-induced multiprotein complex, the inflammasome, resulting in the activation of pro-inflammatory caspase-1 and induction of pyroptotic cell death [5,10]. Defective NLRP1 inflammasome activity is also implicated in autoimmune pathologies [1,6,8,15,17], and has coined the term inflammasomopathies (note that this refers to diseases associated with defective inflammasome proteins in addition to NLRP1, e.g. NLRC4 and NLRP12) [13]. |
| Immuno Process Associations | ||
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| Physiological Functions Comments | |
| Involved in inflammasome formation, caspase-1 activation. |
| Clinically-Relevant Mutations and Pathophysiology
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| General Comments |
| Evidence implicates elevated levels of triglyceride and vldl-cholesterol with activation of the NLRP1 inflammasome in endothelial cells [3,9], and suggests a potential link to atherosclerotic inflammation. Inhibition of the NLRP1 inflammasome has therefore been suggested as a potential molecular mechanism applicable to the treatment of peripheral arterial disease [2,14]. There are also associations between inflammasome function and cancer [7,12,16-17], and evidence that suggests that NLRP1 and NLRP3 inflammasomes are activated in Alzheimer's disease [11]. |
1. Akiyama M, Takeichi T, McGrath JA, Sugiura K. (2017) Autoinflammatory keratinization diseases. J Allergy Clin Immunol, 140 (6): 1545-1547. [PMID:28668225]
2. Bleda S, de Haro J. (2018) Identification of a potential inhibitor of NLRP1 inflammasome for the treatment of peripheral arterial disease. Int J Cardiol, 256: 30. [PMID:29454411]
3. Bleda S, de Haro J, Varela C, Ferruelo A, Acin F. (2016) Elevated levels of triglycerides and vldl-cholesterol provoke activation of nlrp1 inflammasome in endothelial cells. Int J Cardiol, 220: 52-5. [PMID:27372042]
4. Chamaillard M, Girardin SE, Viala J, Philpott DJ. (2003) Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation. Cell Microbiol, 5 (9): 581-92. [PMID:12925128]
5. Chavarría-Smith J, Vance RE. (2015) The NLRP1 inflammasomes. Immunol Rev, 265 (1): 22-34. [PMID:25879281]
6. Grandemange S, Sanchez E, Louis-Plence P, Tran Mau-Them F, Bessis D, Coubes C, Frouin E, Seyger M, Girard M, Puechberty J et al.. (2017) A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). Ann Rheum Dis, 76 (7): 1191-1198. [PMID:27965258]
7. Karki R, Man SM, Kanneganti TD. (2017) Inflammasomes and Cancer. Cancer Immunol Res, 5 (2): 94-99. [PMID:28093447]
8. Maver A, Lavtar P, Ristić S, Stopinšek S, Simčič S, Hočevar K, Sepčić J, Drulović J, Pekmezović T, Novaković I et al.. (2017) Identification of rare genetic variation of NLRP1 gene in familial multiple sclerosis. Sci Rep, 7 (1): 3715. [PMID:28623311]
9. Pan Y, Wang Y, Xu J, Wu J, Chen Q, Zeng G, Zhao G. (2017) TG and VLDL cholesterol activate NLRP1 inflammasome by Nuclear Factor-κB in endothelial cells. Int J Cardiol, 234: 103. [PMID:28062143]
10. Place DE, Kanneganti TD. (2018) Recent advances in inflammasome biology. Curr Opin Immunol, 50: 32-38. [PMID:29128729]
11. Saresella M, La Rosa F, Piancone F, Zoppis M, Marventano I, Calabrese E, Rainone V, Nemni R, Mancuso R, Clerici M. (2016) The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease. Mol Neurodegener, 11: 23. [PMID:26939933]
12. Sharma N, Jha S. (2016) NLR-regulated pathways in cancer: opportunities and obstacles for therapeutic interventions. Cell Mol Life Sci, 73 (9): 1741-64. [PMID:26708292]
13. Sönmez HE, Özen S. (2017) A clinical update on inflammasomopathies. Int Immunol, 29 (9): 393-400. [PMID:28387826]
14. Wang W, Wang C, Gong Y, Zhang X. (2018) Inhibition of NLRP1 inflammasome might be a novel therapeutic target in the treatment of peripheral arterial disease. Int J Cardiol, 256: 29. [PMID:29454409]
15. Yu CH, Moecking J, Geyer M, Masters SL. (2018) Mechanisms of NLRP1-Mediated Autoinflammatory Disease in Humans and Mice. J Mol Biol, 430 (2): 142-152. [PMID:28733143]
16. Zhai Z, Liu W, Kaur M, Luo Y, Domenico J, Samson JM, Shellman YG, Norris DA, Dinarello CA, Spritz RA et al.. (2017) NLRP1 promotes tumor growth by enhancing inflammasome activation and suppressing apoptosis in metastatic melanoma. Oncogene, 36 (27): 3820-3830. [PMID:28263976]
17. Zhong FL, Mamaï O, Sborgi L, Boussofara L, Hopkins R, Robinson K, Szeverényi I, Takeichi T, Balaji R, Lau A et al.. (2016) Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation. Cell, 167 (1): 187-202.e17. [PMID:27662089]
target has curated data in GtoImmuPdb
