NLRC5: A Key Regulator of MHC Class I Expression and Immune Surveillance
Comprehensive gene card, expression, mutations, and disease associations for NLRC5 (NLR family CARD domain containing 5).
Gene Information Card
| Symbol | NLRC5 |
|---|---|
| Full Name | NLR family CARD domain containing 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q13 |
| NCBI Gene ID | 84166 ncbi.nlm.nih.gov/gene/84166 |
| Ensembl ID | ENSG00000140853 |
| UniProt ID | Q86WI3 |
| OMIM ID | 613537 |
| HGNC ID | 16433 |
| Aliases | CITA, NOD4, NOD27, CLR16.1 |
Description
NLRC5 (NLR family CARD domain containing 5) encodes a protein that functions as a key transcriptional activator of MHC class I genes. It is a member of the NLR (nucleotide-binding domain and leucine-rich repeat containing) family and is primarily involved in immune surveillance by regulating antigen presentation. NLRC5 is also implicated in antiviral responses and inflammatory signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency with NLRC5 deficiency | Loss-of-function mutations in NLRC5 impair MHC class I expression, leading to reduced CD8+ T cell activation and increased susceptibility to viral infections. | OMIM #613537; PMID: 25683120 |
| Colorectal cancer | Reduced NLRC5 expression correlates with decreased MHC class I levels and poor prognosis, suggesting immune evasion. | COSMIC; PMID: 28476880 |
| Melanoma | NLRC5 downregulation is associated with loss of antigen presentation and resistance to immunotherapy. | COSMIC; PMID: 29033131 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lung | 6.2 | Low |
| Small intestine | 5.1 | Low |
| Bone marrow | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 8.7 | Embryonic kidney cells |
| HeLa | 6.4 | Cervical cancer cells |
| K562 | 3.2 | Leukemia cells |
| MCF7 | 2.1 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1966C>T (p.Arg656*) | Nonsense | Rare | Loss of function; truncation of CARD domain |
| c.2389G>A (p.Gly797Arg) | Missense | Rare | Likely loss of function; disrupts NOD domain |
| c.3130C>T (p.Arg1044Trp) | Missense | Rare | Uncertain significance; LRR domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg656*) lead to truncated protein lacking functional domains, impairing MHC class I transactivation.
Gain of Function (GOF)
No gain-of-function mutations reported in NLRC5.
Dominant Negative (DN)
No dominant-negative mutations characterized; NLRC5 functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MHC class I antigen presentation (Reactome: R-HSA-983170)
• NOD-like receptor signaling pathway (KEGG: hsa04621)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
Protein Summary
NLRC5 is a 1866-amino acid protein containing an N-terminal CARD domain, a central NACHT domain, and C-terminal leucine-rich repeats (LRRs). It acts as a transcriptional coactivator by binding to the MHC class I promoter and recruiting histone-modifying enzymes. NLRC5 is predominantly expressed in lymphoid tissues and is essential for optimal antigen presentation and CD8+ T cell activation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRC5 Knockout HEK293 Cell Line | EDJ-KQ9999 | Human | 84166 | Details Get a Quote |
| NLRC5 Knockout A-549 Cell Line | EDJ-KQ36961 | Human | 84166 | Details Get a Quote |
| NLRC5 Knockout HCT 116 Cell Line | EDJ-KQ36962 | Human | 84166 | Details Get a Quote |
| NLRC5 Knockout HeLa Cell Line | EDJ-KQ36963 | Human | 84166 | Details Get a Quote |
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