NLRC3: A Negative Regulator of Inflammation and Immune Signaling
Comprehensive gene card for NLRC3 (NLR Family CARD Domain Containing 3) – a key modulator of NF-κB and type I interferon pathways.
Gene Information Card
| Symbol | NLRC3 |
|---|---|
| Full Name | NLR Family CARD Domain Containing 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 197358 ncbi.nlm.nih.gov/gene/197358 |
| Ensembl ID | ENSG00000196419 |
| UniProt ID | Q7Z6L1 |
| OMIM ID | 609354 |
| HGNC ID | 29889 |
| Aliases | NOD3, CLR16.2, NOD-like receptor C3 |
Description
NLRC3 (NLR Family CARD Domain Containing 3) is a member of the NOD-like receptor (NLR) family. It functions as a negative regulator of innate immune signaling, particularly by inhibiting NF-κB and type I interferon pathways. NLRC3 attenuates STING-dependent signaling and suppresses inflammatory responses, playing a role in maintaining immune homeostasis. It is expressed in various immune and non-immune tissues and has been implicated in cancer, autoimmune diseases, and infectious diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | NLRC3 downregulation leads to increased NF-κB activation and tumor progression. | NCBI Gene, COSMIC |
| Systemic Lupus Erythematosus | NLRC3 variants may alter interferon signaling regulation. | OMIM, ClinVar |
| Inflammatory Bowel Disease | Reduced NLRC3 expression correlates with enhanced intestinal inflammation. | NCBI Gene, UniProt |
| Viral Infections | NLRC3 inhibits STING-mediated antiviral responses. | UniProt, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lung | 8.3 | Low |
| Colon | 6.7 | Low |
| Small Intestine | 5.9 | Low |
| Whole Blood | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | Macrophage-like |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous |
| Jurkat (T-cell) | 8.9 | Moderate |
| HCT116 (colon cancer) | 6.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | 0.01% | Unknown; predicted damaging |
| c.1483G>A (p.Gly495Arg) | Missense | 0.005% | May affect protein stability |
| c.1960_1962del (p.Lys654del) | In-frame deletion | <0.001% | Loss of function in NF-κB inhibition |
Mutation functional classification
Loss of Function (LOF)
Deletions or missense mutations that impair NLRC3's ability to inhibit NF-κB or STING signaling, leading to enhanced inflammation.
Gain of Function (GOF)
Not well documented; potential hypermorphic variants could excessively suppress immune responses.
Dominant Negative (DN)
Truncating or missense mutations that interfere with wild-type NLRC3 function, reducing negative regulation.
View complete mutation data：
Gene Ontology (GO)
| • negative regulation of NF-κB transcription factor activity | • negative regulation of type I interferon production |
| • innate immune response | • signal transduction |
| • protein binding | • ATP binding |
Pathways
• NOD-like receptor signaling pathway (KEGG: hsa04621)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
• STING pathway (Reactome: R-HSA-1834941)
Protein Summary
NLRC3 encodes a 992-amino acid protein containing an N-terminal CARD domain, a central NACHT domain, and C-terminal LRR repeats. It localizes to the cytoplasm and negatively regulates STING-dependent interferon induction and NF-κB activation. The protein is expressed in immune cells and epithelial tissues, and its loss is associated with increased inflammatory signaling and tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRC3 Knockout HEK293 Cell Line | EDJ-KQ3417 | Human | 197358 | Details Get a Quote |
| NLRC3 Knockout HeLa Cell Line | EDJ-KQ58982 | Human | 197358 | Details Get a Quote |
| NLRC3 Knockout A-549 Cell Line | EDJ-KQ67466 | Human | 197358 | Details Get a Quote |
| NLRC3 Knockout HCT 116 Cell Line | EDJ-KQ75862 | Human | 197358 | Details Get a Quote |
