NLRP2 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the NLRP2 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | NLRP2 |
|---|---|
| Full Name | NACHT, LRR and PYD domains-containing protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.42 |
| NCBI Gene ID | 55655 ncbi.nlm.nih.gov/gene/55655 |
| Ensembl ID | ENSG00000122585 |
| UniProt ID | Q9NX02 |
| OMIM ID | 609364 |
| HGNC ID | 22948 |
| Aliases | NBS1, NALP2, PYPAF2, CLR19.9 |
Description
The NLRP2 gene encodes a member of the NLR (nucleotide-binding domain and leucine-rich repeat containing) family, which are critical components of the innate immune system. NLRP2 is involved in the regulation of inflammation and apoptosis, and it functions as a component of the inflammasome, a multiprotein complex that activates inflammatory caspases. The protein contains an N-terminal pyrin domain (PYD), a central NACHT domain, and C-terminal leucine-rich repeats (LRRs). NLRP2 is expressed in various tissues, with notable expression in immune cells and reproductive tissues. Mutations in NLRP2 have been associated with susceptibility to certain inflammatory conditions and reproductive disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial cold autoinflammatory syndrome 2 (FCAS2) | Gain-of-function mutations in NLRP2 lead to constitutive activation of the inflammasome, resulting in excessive IL-1β production and systemic inflammation. | OMIM: 609364; ClinVar |
| Recurrent hydatidiform mole | Biallelic loss-of-function mutations in NLRP2 impair normal placental development, leading to molar pregnancy. | OMIM: 609364; ClinVar |
| Susceptibility to inflammatory bowel disease (IBD) | Polymorphisms in NLRP2 may alter inflammasome activity, contributing to chronic intestinal inflammation. | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Spleen | 8.7 | Low |
| Lung | 6.5 | Low |
| Placenta | 5.9 | Low |
| Bone marrow | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; used in inflammasome studies |
| HeLa (cervical cancer) | 8.1 | Moderate expression |
| A549 (lung carcinoma) | 5.4 | Low expression |
| MCF7 (breast cancer) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg779Cys | Missense | Rare | Gain-of-function; associated with FCAS2 |
| p.Leu582Phe | Missense | Rare | Gain-of-function; associated with FCAS2 |
| c.1960delC | Frameshift | Very rare | Loss-of-function; associated with recurrent hydatidiform mole |
| p.Gln315Ter | Nonsense | Very rare | Loss-of-function; associated with recurrent hydatidiform mole |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) impair NLRP2's ability to regulate inflammasome activity, leading to dysregulated inflammation and reproductive defects.
Gain of Function (GOF)
Gain-of-function mutations (e.g., missense in NACHT domain) cause constitutive inflammasome activation, resulting in autoinflammatory phenotypes.
Dominant Negative (DN)
Dominant-negative effects have not been clearly documented for NLRP2; most pathogenic mutations are either gain- or loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein homodimerization activity |
| • protein kinase binding | • inflammasome complex |
| • regulation of inflammatory response | • apoptotic process |
| • immune response | • negative regulation of NF-kappaB transcription factor activity |
Pathways
• NOD-like receptor signaling pathway
• Inflammasome pathway
• IL-1 beta production pathway
Protein Summary
NLRP2 is a 1062-amino acid protein with a molecular weight of approximately 120 kDa. It contains a pyrin domain (PYD) at the N-terminus, a NACHT domain (including an ATPase domain), and C-terminal leucine-rich repeats (LRRs). The protein localizes to the cytoplasm and is involved in the assembly of the inflammasome complex, which activates caspase-1 and promotes the cleavage of pro-IL-1β and pro-IL-18 into their active forms. NLRP2 also plays a role in regulating NF-κB signaling and apoptosis. Its expression is particularly high in immune cells and reproductive tissues, suggesting specialized functions in these contexts.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRP2 Knockout HEK293 Cell Line | EDJ-KQ14437 | Human | 55655 | Details Get a Quote |
| NLRP2B Knockout HEK293 Cell Line | EDJ-KQ14438 | Human | 286430 | Details Get a Quote |
| NLRP2 Knockout A-549 Cell Line | EDJ-KQ44656 | Human | 55655 | Details Get a Quote |
| NLRP2 Knockout HCT 116 Cell Line | EDJ-KQ43394 | Human | 55655 | Details Get a Quote |
| NLRP2 Knockout HeLa Cell Line | EDJ-KQ56613 | Human | 55655 | Details Get a Quote |
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