NLRP12 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the NLRP12 gene, its protein product, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | NLRP12 |
|---|---|
| Full Name | NLR family pyrin domain containing 12 |
| Gene Type | protein coding |
| Chromosomal Location | 19q13.42 |
| NCBI Gene ID | 91662 ncbi.nlm.nih.gov/gene/91662 |
| Ensembl ID | ENSG00000142405 |
| UniProt ID | P59046 |
| OMIM ID | 609648 |
| HGNC ID | 22938 |
| Aliases | RNO, RNO2, CLR19.3, NALP12, Monarch-1, PYPAF7 |
Description
The NLRP12 gene encodes a member of the NLR (nucleotide-binding domain and leucine-rich repeat containing) family, specifically the NLRP subfamily. NLRP12 is a cytoplasmic protein that functions as a pattern recognition receptor (PRR) and plays a role in innate immunity and inflammation. It is involved in the regulation of NF-kappaB and MAPK signaling pathways, acting as a negative regulator of inflammatory responses. Mutations in NLRP12 are associated with familial cold autoinflammatory syndrome 2 (FCAS2), a periodic fever syndrome. The protein is also implicated in cancer and autoimmune diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial cold autoinflammatory syndrome 2 (FCAS2) | Missense mutations in NLRP12 lead to dysregulated inflammasome activation and increased NF-kappaB signaling, causing excessive inflammation. | ClinVar, OMIM |
| Periodic fever, familial (Hibernian fever) | NLRP12 mutations are associated with periodic fever syndromes, likely through altered cytokine production. | ClinVar, OMIM |
| Colorectal cancer | NLRP12 acts as a tumor suppressor in the colon; loss of function leads to increased inflammation and tumorigenesis. | COSMIC, PubMed (via NCBI) |
| Atopic dermatitis | NLRP12 variants may contribute to skin inflammation through dysregulated immune responses. | ClinVar, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | 5.2 | Low |
| Spleen | 3.1 | Low |
| Lymph node | 2.8 | Low |
| Bone marrow | 2.5 | Low |
| Lung | 1.9 | Low |
| Liver | 1.2 | Low |
| Brain | 0.8 | Not detected |
| Heart | 0.6 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 8.5 | High expression; used in inflammasome studies |
| K-562 (leukemia) | 4.2 | Moderate expression |
| HeLa (cervical cancer) | 2.1 | Low expression |
| A549 (lung cancer) | 1.5 | Low expression |
| MCF7 (breast cancer) | 1.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1054C>T (p.Arg352Trp) | Missense | Rare (0.1% in gnomAD) | Associated with FCAS2; increases NF-kB activity |
| c.2072G>A (p.Arg691His) | Missense | Rare (0.05% in gnomAD) | Likely pathogenic; disrupts protein function |
| c.2173C>T (p.Arg725Trp) | Missense | Rare (0.02% in gnomAD) | Reported in FCAS2; alters inflammasome regulation |
| c.1105C>T (p.Arg369Ter) | Nonsense | Very rare | Loss of function; leads to truncated protein |
| c.1494del (p.Glu499fs) | Frameshift | Very rare | Loss of function; associated with colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NLRP12, such as nonsense or frameshift variants, result in reduced or absent protein function. This leads to impaired negative regulation of NF-kB and increased inflammatory cytokine production, contributing to autoinflammatory diseases and cancer.
Gain of Function (GOF)
Gain-of-function mutations are less common but may lead to constitutive activation of the inflammasome, resulting in excessive IL-1β production and severe inflammation. Some missense variants in the NACHT domain are suspected to have this effect.
Dominant Negative (DN)
Dominant-negative mutations in NLRP12 can interfere with the function of the wild-type allele, disrupting protein-protein interactions and leading to dysregulated signaling. This mechanism is proposed for certain missense mutations in the leucine-rich repeat domain.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein binding |
| • zinc ion binding | • signal transducer activity |
| • inflammasome complex | • cytoplasm |
| • nucleus | • negative regulation of NF-kappaB transcription factor activity |
| • regulation of inflammatory response | • innate immune response |
| • apoptotic process |
Pathways
• NOD-like receptor signaling pathway
• NF-kappa B signaling pathway
• MAPK signaling pathway
• Inflammasome pathway
• Innate Immune System
Protein Summary
NLRP12 is a 1,061-amino acid protein containing an N-terminal pyrin domain (PYD), a central NACHT domain, and C-terminal leucine-rich repeats (LRRs). It is a key regulator of innate immunity, acting as a negative regulator of NF-kB and MAPK signaling. NLRP12 also forms an inflammasome complex with ASC and caspase-1, leading to IL-1β and IL-18 maturation. Its expression is primarily in immune cells, and it is involved in inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRP12 Knockout HEK293 Cell Line | EDJ-KQ10770 | Human | 91662 | Details Get a Quote |
| NLRP12 Knockout HeLa Cell Line | EDJ-KQ57808 | Human | 91662 | Details Get a Quote |
| NLRP12 Knockout A-549 Cell Line | EDJ-KQ66304 | Human | 91662 | Details Get a Quote |
| NLRP12 Knockout HCT 116 Cell Line | EDJ-KQ74728 | Human | 91662 | Details Get a Quote |
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