NLRP4: A Key Regulator of Inflammasome Signaling and Immune Response
Comprehensive gene card for NLRP4 (NLR family pyrin domain containing 4) – genomic context, expression, mutations, and clinical relevance.
Gene Information Card
| Symbol | NLRP4 |
|---|---|
| Full Name | NLR family pyrin domain containing 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.43 |
| NCBI Gene ID | 147945 ncbi.nlm.nih.gov/gene/147945 |
| Ensembl ID | ENSG00000105669 |
| UniProt ID | Q96MN2 |
| OMIM ID | 609886 |
| HGNC ID | 22945 |
| Aliases | CLR19.5, NALP4, PAN2, PYPAF4 |
Description
NLRP4 (NLR family pyrin domain containing 4) is a member of the NOD-like receptor (NLR) family, characterized by an N-terminal pyrin domain (PYD), a central NACHT domain, and C-terminal leucine-rich repeats (LRRs). It functions as a pattern recognition receptor involved in the regulation of inflammasome assembly and inflammatory signaling. NLRP4 can both positively and negatively modulate immune responses, and its dysregulation has been implicated in autoimmune diseases and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoinflammatory syndromes | Altered inflammasome activation leading to excessive IL-1β production | OMIM 609886; ClinVar |
| Colorectal cancer | NLRP4 downregulation may impair tumor immune surveillance | COSMIC; NCBI Gene |
| Systemic lupus erythematosus (SLE) | Polymorphisms in NLRP4 associated with increased disease risk | OMIM; PubMed |
| Gastric cancer | Hypermethylation of NLRP4 promoter linked to reduced expression | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lung | 8.3 | Low |
| Whole blood | 6.1 | Low |
| Bone marrow | 15.2 | Medium |
| Lymph node | 10.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 18.4 | High expression; used in inflammasome studies |
| HeLa (cervical) | 5.2 | Low expression |
| A549 (lung) | 7.8 | Moderate expression |
| K562 (leukemia) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Trp) | Missense | <0.01% | Unknown; predicted damaging by SIFT |
| c.1456G>A (p.Glu486Lys) | Missense | <0.01% | May alter NACHT domain function |
| c.2101_2102insA | Frameshift | <0.01% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., c.2101_2102insA) predicted to cause protein truncation and loss of function.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance inflammasome activity.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein homodimerization activity |
| • pyrin domain binding | • innate immune response |
| • inflammatory response | • NLRP4 inflammasome complex assembly |
Pathways
• NOD-like receptor signaling pathway (KEGG hsa04621)
• Inflammasome pathway (Reactome R-HSA-844456)
Protein Summary
NLRP4 encodes a 1,002-amino-acid protein containing an N-terminal pyrin domain (PYD), a central NACHT domain, and C-terminal leucine-rich repeats (LRRs). It acts as a scaffold for inflammasome formation, recruiting ASC and pro-caspase-1 via PYD-PYD interactions. NLRP4 can both activate and inhibit caspase-1-dependent IL-1β secretion, depending on cellular context. The protein is predominantly cytoplasmic and expressed in immune tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRP4 Knockout HEK293 Cell Line | EDJ-KQ9990 | Human | 147945 | Details Get a Quote |
| NLRP4 Knockout HeLa Cell Line | EDJ-KQ58591 | Human | 147945 | Details Get a Quote |
| NLRP4 Knockout A-549 Cell Line | EDJ-KQ67078 | Human | 147945 | Details Get a Quote |
| NLRP4 Knockout HCT 116 Cell Line | EDJ-KQ75483 | Human | 147945 | Details Get a Quote |
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