NLRP6: A Key Regulator of Innate Immunity and Intestinal Homeostasis
Comprehensive gene card for NLRP6, including expression, mutations, and disease associations.
Gene Information Card
| Symbol | NLRP6 |
|---|---|
| Full Name | NLR family pyrin domain containing 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 171389 ncbi.nlm.nih.gov/gene/171389 |
| Ensembl ID | ENSG00000175130 |
| UniProt ID | P59044 |
| OMIM ID | 609650 |
| HGNC ID | 22944 |
| Aliases | PYPAF5, PAN3, CLR11.4 |
Description
NLRP6 (NLR family pyrin domain containing 6) is a member of the NOD-like receptor (NLR) family, functioning as a cytoplasmic pattern recognition receptor. It plays a critical role in innate immunity, particularly in the regulation of intestinal homeostasis, inflammasome activation, and modulation of inflammatory responses. NLRP6 is highly expressed in the gastrointestinal tract and is involved in maintaining epithelial barrier integrity, mucus secretion, and host defense against pathogens. Dysregulation of NLRP6 has been linked to inflammatory bowel disease, colorectal cancer, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | NLRP6 loss-of-function mutations or reduced expression impair inflammasome activation and IL-18 production, promoting tumorigenesis and epithelial barrier dysfunction. | PMID: 21903775, 26005855 |
| Inflammatory Bowel Disease (IBD) | NLRP6 deficiency leads to altered gut microbiota composition, reduced mucus secretion, and increased susceptibility to colitis. | PMID: 21903775, 26005855 |
| Metabolic Syndrome | NLRP6 regulates intestinal inflammation and metabolic endotoxemia; deficiency exacerbates diet-induced obesity and insulin resistance. | PMID: 26005855 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 12.5 | Medium |
| Small Intestine | 10.2 | Medium |
| Stomach | 6.8 | Low |
| Liver | 3.1 | Low |
| Lung | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (Colorectal adenocarcinoma) | 8.4 | High expression |
| HT-29 (Colorectal adenocarcinoma) | 6.2 | Moderate expression |
| HCT 116 (Colorectal carcinoma) | 4.1 | Low expression |
| HEK 293 (Embryonic kidney) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.1456G>A (p.Gly486Arg) | Missense | <0.01% | Unknown; predicted damaging |
| c.2020_2021del (p.Leu674fs) | Frameshift | <0.01% | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg335*, p.Leu674fs) result in truncated or non-functional NLRP6 protein, impairing inflammasome assembly and IL-18 secretion.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NLRP6 in curated databases.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for NLRP6.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein homodimerization activity |
| • pyrin domain binding | • innate immune response |
| • inflammatory response | • regulation of cytokine production |
| • intestinal epithelial cell differentiation | • mucus secretion |
Pathways
• NOD-like receptor signaling pathway (KEGG: hsa04621)
• Inflammasome pathway (Reactome: R-HSA-844456)
• Interleukin-18 signaling (Reactome: R-HSA-6785807)
Protein Summary
NLRP6 is a 892-amino acid protein containing an N-terminal pyrin domain (PYD), a central NACHT domain, and C-terminal leucine-rich repeats (LRRs). It functions as a scaffold for inflammasome assembly, recruiting ASC and caspase-1 to promote IL-1β and IL-18 maturation. NLRP6 is predominantly expressed in intestinal epithelial cells and is essential for maintaining gut homeostasis through regulation of mucus production, antimicrobial peptide secretion, and microbiota composition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRP6 Knockout HCT 116 Cell Line | EDJ-KQ21 | Human | 171389 | Details Get a Quote |
| NLRP6 Knockout HEK293 Cell Line | EDJ-KQ1132 | Human | 171389 | Details Get a Quote |
| NLRP6 Knockout HeLa Cell Line | EDJ-KQ58953 | Human | 171389 | Details Get a Quote |
| NLRP6 Knockout A-549 Cell Line | EDJ-KQ67440 | Human | 171389 | Details Get a Quote |
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