Top ▲

NLRP1

Click here for help

Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1768

Nomenclature: NLRP1

Family: NOD-like receptor family

Contents:

Gene and Protein Information Click here for help
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 Click here for help
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 Click here for help
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
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Physiological Functions Comments
Involved in inflammasome formation, caspase-1 activation.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Addison disease
Synonyms: Hypoadrenocorticism, familial [OMIM: 240200]
OMIM: 240200
Orphanet: ORPHA85138
Disease:  Alzheimer disease
Synonyms: Alzheimer's disease [Disease Ontology: DOID:10652]
Disease Ontology: DOID:10652
OMIM: 104300
Disease:  Autoimmune thyroid disorders
Disease:  Celiac disease
Disease Ontology: DOID:10608
Disease:  Congenital toxoplasmosis
Disease Ontology: DOID:13336
Orphanet: ORPHA858
Disease:  Corneal intraepithelial dyskeratosis and ectodermal dysplasia; CIDED
Synonyms: Corneal intraepithelial dyskeratosis with palmoplantar hyperkeratosis and laryngeal dyskeratosis [Orphanet: ORPHA352662]
OMIM: 615225
Orphanet: ORPHA352662
Disease:  Diabetes mellitus, insulin-dependent; IDDM
Synonyms: Type 1 diabetes mellitus [Disease Ontology: DOID:9744]
Disease Ontology: DOID:9744
OMIM: 222100
Disease:  Psoriasis
Description: A long-term autoimmune disease characterized by patches of red, itchy, and scaly skin. Five types of psoriasis are recognised: plaque (psoriasis vulgari), guttate, inverse, pustular, and erythrodermic, with plaque psoriasis being the most common type.
Disease Ontology: DOID:8893
Disease:  Rheumatoid arthritis
Disease Ontology: DOID:7148
OMIM: 180300
Disease:  Systemic lupus erythematosus
Description: SLE is a complex autoimmune disease that is characterised by inflammation of various connective tissues, and symptoms include dermatitis, arthritis, inflammation of the kidneys (glomerulonephritis), vasculitis, inflammation of the tissue surrounding the heart, and seizures. It is caused by the production of autoantibodies against widely expressed nuclear, cytoplasmic, and cell surface molecules. Extracellular RNA in the circulation in combination with the presence of autoantibodies potently stimulates interferon production and immune system activation.
Disease Ontology: DOID:9074
OMIM: 152700
Orphanet: ORPHA536
Disease:  Systemic scleroderma
Description: A complex heterogeneous fibrosing autoimmune disorder characterised by extensive fibrosis, vasculopathy, and immune dysfunction.
Synonyms: Scleroderma, familial progressive [OMIM: 181750]
Systemic sclerosis [Orphanet: ORPHA90291]
Disease Ontology: DOID:418
OMIM: 181750
Orphanet: ORPHA90291
Disease:  Temporal arteritis
Description: This is a chronic inflammatory disease of medium-large arteries. Costicosteroids are the primary treatment for GCA, however blockade of the IL-6/IL-6R pathway has proven an effective alternative to costicosteroids. The anti-IL-6Rα monoclonal antibody tocilizumab was approved for GCA by the FDA in 2017. IL-6 production is downstream of GM-CSF and does not address all of the underlying causes of inflammation in GCA, and the GM-CSF pathway itself is now an active therapeutic target for this indication.
Synonyms: Giant cell arteritis [Orphanet: ORPHA397]
Disease Ontology: DOID:13375
OMIM: 187360
Orphanet: ORPHA397
Disease:  Vitiligo-associated multiple autoimmune disease susceptibility 1; VAMAS1
Synonyms: Vitiligo-associated autoimmune disease [Orphanet: ORPHA247871]
OMIM: 606579
Orphanet: ORPHA247871
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].

References

Show »

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]

Contributors

Show »

How to cite this page