NLRC4
NLR Family CARD Domain Containing 4
Gene Information Card
| Symbol | NLRC4 |
|---|---|
| Full Name | NLR Family CARD Domain Containing 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p22.3 |
| NCBI Gene ID | 58484 ncbi.nlm.nih.gov/gene/58484 |
| Ensembl ID | ENSG00000091106 |
| UniProt ID | Q9NPP4 |
| OMIM ID | 606831 |
| HGNC ID | 16412 |
| Aliases | CLR2.1, CLAN, CLAN1, CLANB, IPAF, CARD12, CLAN2, CLANA |
Description
NLRC4 (NLR Family CARD Domain Containing 4) encodes a member of the NLR (nucleotide-binding and leucine-rich repeat) family of proteins. NLRC4 is a key component of the inflammasome, a multiprotein complex that activates caspase-1 in response to bacterial flagellin and type III secretion system components, leading to pyroptosis and cytokine release. Mutations in NLRC4 are associated with autoinflammatory disorders and susceptibility to infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoinflammation with Infantile Enterocolitis (AIFEC) | Gain-of-function mutations in NLRC4 cause constitutive inflammasome activation, leading to excessive IL-1β and IL-18 production. | OMIM #616050 |
| Familial Cold Autoinflammatory Syndrome 4 (FCAS4) | Missense mutations in NLRC4 result in enhanced inflammasome assembly and IL-1β secretion upon cold exposure. | OMIM #616115 |
| Macrophage Activation Syndrome (MAS) | NLRC4 gain-of-function mutations can trigger uncontrolled immune activation and hemophagocytic lymphohistiocytosis. | PubMed: 25217960 |
| Legionella pneumophila Infection | NLRC4 detects bacterial flagellin and type IV secretion system components, restricting intracellular replication. | PubMed: 16916647 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.8 | Medium |
| Lung | 8.2 | Medium |
| Spleen | 7.5 | Medium |
| Whole Blood | 6.1 | Low |
| Small Intestine | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression |
| HL-60 (promyeloblast) | 11.4 | Medium expression |
| K-562 (lymphoblast) | 8.9 | Medium expression |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Val341Ala | Missense | Rare | Gain-of-function; associated with AIFEC |
| p.Thr337Ser | Missense | Rare | Gain-of-function; associated with FCAS4 |
| p.His443Pro | Missense | Rare | Gain-of-function; associated with MAS |
| p.Arg288Trp | Missense | Rare | Loss-of-function; associated with susceptibility to Legionella |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., p.Arg288Trp) impair NLRC4 activation, reducing inflammasome response to bacterial ligands.
Gain of Function (GOF)
Common missense mutations (e.g., p.Val341Ala, p.Thr337Ser) cause constitutive inflammasome activation, leading to autoinflammatory diseases.
Dominant Negative (DN)
Not reported for NLRC4.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • cysteine-type endopeptidase activator activity involved in apoptotic process |
| • inflammasome complex | • innate immune response |
| • protein homooligomerization | • regulation of inflammatory response |
Pathways
• NOD-like receptor signaling pathway (KEGG: hsa04621)
• Salmonella infection (KEGG: hsa05132)
• Legionellosis (KEGG: hsa05134)
• Pyroptosis (Reactome: R-HSA-5620971)
Protein Summary
NLRC4 is a 1024-amino acid protein containing an N-terminal CARD domain, a central NACHT domain, and C-terminal leucine-rich repeats (LRRs). It functions as a cytosolic sensor of bacterial flagellin and type III secretion system rod/needle proteins. Upon ligand detection, NLRC4 oligomerizes and recruits pro-caspase-1 via ASC or directly, forming the NLRC4 inflammasome. This complex activates caspase-1, which cleaves pro-IL-1β and pro-IL-18 into active cytokines and induces pyroptosis. NLRC4 is predominantly expressed in myeloid cells and intestinal epithelium.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRC4 Knockout HEK293 Cell Line | EDJ-KQ505 | Human | 58484 | Details Get a Quote |
| NLRC4 Knockout HeLa Cell Line | EDJ-KQ56937 | Human | 58484 | Details Get a Quote |
| NLRC4 Knockout A-549 Cell Line | EDJ-KQ65443 | Human | 58484 | Details Get a Quote |
| NLRC4 Knockout HCT 116 Cell Line | EDJ-KQ73880 | Human | 58484 | Details Get a Quote |
| Nlrc4 Knockout IBMDM Cell Line | EDC07958 | Mouse | 268973 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
