NLRX1: A Key Regulator of Innate Immunity and Mitochondrial Homeostasis
Comprehensive gene card for NLRX1 (NLR family member X1), a unique mitochondrial NOD-like receptor involved in antiviral signaling, inflammation, and cellular stress responses.
Gene Information Card
| Symbol | NLRX1 |
|---|---|
| Full Name | NLR family member X1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 79671 ncbi.nlm.nih.gov/gene/79671 |
| Ensembl ID | ENSG00000160703 |
| UniProt ID | Q86UT6 |
| OMIM ID | 611947 |
| HGNC ID | 29890 |
| Aliases | NOD9, NOD26, CLRX1.1 |
Description
NLRX1 (NLR family member X1) encodes a member of the NOD-like receptor (NLR) family of cytoplasmic pattern recognition receptors. Unlike other NLRs, NLRX1 localizes to the mitochondrial matrix and modulates innate immune signaling, including type I interferon production, NF-κB activation, and reactive oxygen species (ROS) generation. It acts as a negative regulator of antiviral responses and is implicated in inflammatory diseases, cancer, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease (IBD) | NLRX1 deficiency leads to increased NF-κB activation and pro-inflammatory cytokine production, exacerbating intestinal inflammation. | PMID: 26944022 |
| Hepatocellular carcinoma | NLRX1 suppresses tumor growth by inhibiting NF-κB and JNK signaling; reduced expression correlates with poor prognosis. | PMID: 25944712 |
| Viral infections (e.g., Influenza A) | NLRX1 inhibits MAVS-dependent antiviral signaling, reducing type I interferon production and promoting viral replication. | PMID: 21957124 |
| Type 2 diabetes | NLRX1 modulates mitochondrial ROS and insulin sensitivity; polymorphisms associated with metabolic traits. | PMID: 28077573 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lung | 10.2 | Medium |
| Liver | 8.9 | Low |
| Heart | 6.3 | Low |
| Brain | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression in embryonic kidney cells |
| HeLa | 11.2 | Moderate expression in cervical cancer cells |
| HepG2 | 9.8 | Moderate expression in liver cancer cells |
| THP-1 | 7.5 | Low expression in monocytic leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | 0.001% (gnomAD) | May alter protein stability; associated with altered immune signaling |
| c.1246G>A (p.Gly416Ser) | Missense | 0.002% (gnomAD) | Potential loss-of-function; linked to reduced NF-κB inhibition |
| c.1483C>T (p.Arg495*) | Nonsense | <0.001% | Truncating mutation; likely loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg495*, p.Gly416Ser) that impair NLRX1's ability to inhibit NF-κB or MAVS signaling, leading to enhanced inflammation or antiviral responses.
Gain of Function (GOF)
Not well characterized; no confirmed gain-of-function mutations reported in literature or databases.
Dominant Negative (DN)
No dominant-negative mutations have been described for NLRX1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005739 (mitochondrion) | • GO:0043065 (positive regulation of apoptotic process) |
| • GO:0032481 (negative regulation of type I interferon production) | • GO:0043123 (positive regulation of I-kappaB kinase/NF-kappaB signaling) |
| • GO:0005515 (protein binding) |
Pathways
• RIG-I/MDA5-mediated induction of interferon-alpha/beta (Reactome: R-HSA-168928)
• NF-kappaB signaling (KEGG: hsa04064)
• Mitochondrial ROS production and apoptosis (WikiPathways: WP4254)
Protein Summary
NLRX1 is a 975-amino acid protein (UniProt Q86UT6) localized to the mitochondrial matrix. It contains an N-terminal NACHT domain and a C-terminal leucine-rich repeat (LRR) domain. Unlike other NLRs, it lacks a canonical PYD or CARD domain. NLRX1 interacts with mitochondrial proteins such as MAVS and TUFM to regulate innate immune signaling, ROS production, and apoptosis. Its expression is highest in immune tissues (spleen, lung) and is dysregulated in cancer and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRX1 Knockout HEK293 Cell Line | EDJ-KQ14442 | Human | 79671 | Details Get a Quote |
| NLRX1 Knockout A-549 Cell Line | EDC07707 | Human | 79671 | Details Get a Quote |
| NLRX1 Knockout HCT 116 Cell Line | EDJ-KQ44659 | Human | 79671 | Details Get a Quote |
| NLRX1 Knockout HeLa Cell Line | EDJ-KQ44660 | Human | 79671 | Details Get a Quote |
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