DefinitionThis section has been translated automatically.
The NLRP12 gene (NLRP12 stands for "NLR Family Pyrin Domain Containing 12") is a protein-coding gene located on chromosome 19q13.42. The NLRP12 gene encodes a member of the so-called CATERPILLER family (older name for NLR proteins) of cytoplasmic proteins.
A new class of (systemic) autoinflammatory syndromes (SAIDs) are referred to as NLRP12-associated diseases (NLRP12AD). The etiopathology of this special group of diseases is based on mutations in the NLRP12 gene. Excessive increases in IL-1beta secretion (80-175 fold) cause the inflammatory symptoms of the disease. In these patients, a dramatic improvement in symptoms can be achieved with Anakinra.
General informationThis section has been translated automatically.
The encoded NLRP12 protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain and a C-terminal leucine-rich repeat region, acts as an anti-inflammatory factor by suppressing inflammatory reactions in activated monocytes.
Mutations in this gene, which cause a deficiency of the encoded protein, cause familial autoinflammatory cold syndrome type 2 (see below Familial cold urticaria).
PathophysiologyThis section has been translated automatically.
The encoded NLRP12 protein is mainly expressed in dendritic cells and macrophages and inhibits both canonical and non-canonical NF-kappa-B and ERK activation pathways. It acts as a negative regulator of NOD2 by driving its degradation via the proteasome pathway. In turn, the encoded protein promotes bacterial tolerance.
Furthermore, NLRP12 inhibits DDX58-mediated immune signaling against RNA viruses by reducing 'Lys-63'-linked DDX58 activation mediated by the E3 ubiquitin ligase TRIM25, but enhancing 'Lys-48'-linked DDX58 degradation mediated by the E3 ubiquitin ligase RNF125. Also acts as a negative regulator of the inflammatory response to mitigate obesity and obesity-associated diseases in adipose tissue.
LiteratureThis section has been translated automatically.
- Borghini S et al. Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation. Arthritis Rheum. 63: 830-839.
- Jeru I et al. (2008) Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Nat Acad Sci 105: 1614-1619.
- Jeru I et al. (2011) Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes. Arthritis Rheum 63: 1459-1464.
- Lich JD et al. (2007) CATERPILLER (NLR) family members as positive and negative regulators of inflammatory responses. Proc Am Thorac Soc 4:263-266.
- Shen M et al. (2017) NLRP12 autoinflammatory disease: a Chinese case series and literature review. Clin Rheum 36: 1661-1667.
- Vitale A et al. (2013) Rare NLRP12 variants associated with the NLRP12-autoinflammatory disorder phenotype: an Italian case series. Clin Exp Rheum 31: 155-156.
- Xia X et al. (2016) Identification of a novel NLRP12 nonsense mutation (Trp408X) in the e