Alt. symbols: NALP12 | RNO2 | PYPAF7 | Monarch1 | PAN6 | CLR19.3

Approved name: NLR family pyrin domain containing 12
Alt. names: NACHT, leucine rich repeat and PYD containing 12 | nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 12

Location: 19q13.42: 53792139 - 53824403 (-)
Gene type: protein_coding, 6 transcripts.

Scores: LoFtool: 0.275000 | pLI: 0.00000000 | LOEUF: 1.355

HGNC: 22938 | Infevers

NCBI: 91662, RefSeq: NG_008651.2

Ensembl: ENSG00000142405.24

LRG_181 | Status: public

OMIM: 609648

Expression | ProteinAtlas

Gene Ontology (GO)

• Molecular function:
• Cell component: cytoplasm [GO:0005737]
• Biological process: negative regulation of canonical NF-kappaB signal transduction [GO:0043124]; negative regulation of inflammatory response [GO:0050728]; cellular response to cytokine stimulus [GO:0071345]; positive regulation of MHC class I biosynthetic process [GO:0045345]

Normal function

The NLRP12 gene encodes the protein monarch-1, a member of a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins, which are mainly found in the cytoplasm of certain types of leukocytes. NLR proteins help to regulate the immune system's response to injury, toxins, or invasion by microorganisms. Unlike most NLR proteins that promote increased activity by the immune system, monarch-1 inhibits the release of certain cytokines that are involved in the process of inflammation.

Dysfunction and disease

Heterozygous loss-of-function (LOF) mutations in NLRP12 have been associated with Familial cold autoinflammatory syndrome 2 (FCAS2) [OMIM: 611762], an extremely rare AD inherited disorder mainly characterized by recurrent episodes of fever and inflammation. The first reported patients suffered from arthralgia, periodic fever, and cold-induced urticaria, with spontaneous improvement during adolescence and functional studies demonstrating that their variants exerted a deleterious effect on NF-kapp aB signaling (PMID: 18230725). Since then, additional nonsense and missense NLRP12 variants have been identified in individuals with periodic fever syndromes, cold-induced autoinflammatory disease and even common variable immunodeficiency (CVID). It has been proposed that these latter mutations do not impair NF-kappaB activation so much as trigger speck formation and activation of caspase 1 signaling, but a unifying understanding of NLRP12-related pathogenesis remains elusive. [Load More]