NCR3LG1 (NK Cell Receptor 3 Ligand 1)
A key immune checkpoint ligand involved in tumor immune evasion and potential therapeutic target
Gene Information Card
| Symbol | NCR3LG1 |
|---|---|
| Full Name | NK cell receptor 3 ligand 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 100506658 ncbi.nlm.nih.gov/gene/100506658 |
| Ensembl ID | ENSG00000255374 |
| UniProt ID | A6NNM7 |
| OMIM ID | 616612 |
| HGNC ID | HGNC:37216 |
| Aliases | B7-H6, DKFZp686K24198 |
Description
NCR3LG1 (also known as B7-H6) encodes a member of the B7 family of immune checkpoint ligands. It is a ligand for the natural killer (NK) cell receptor NCR3 (NKp30). NCR3LG1 is not expressed in normal tissues but is selectively expressed on tumor cells, where it triggers NK cell activation and cytotoxicity. However, tumor cells can shed soluble NCR3LG1 to evade immune surveillance. This gene plays a critical role in innate immunity and cancer biology.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various solid tumors) | Tumor cells express NCR3LG1 on the surface, engaging NKp30 on NK cells to induce killing. However, shedding of soluble NCR3LG1 (sB7-H6) impairs NK cell function, promoting immune evasion. | Multiple studies (e.g., PMID: 19609247, 26033031) show NCR3LG1 expression in tumor cell lines and primary tumors, and elevated serum sB7-H6 correlates with poor prognosis in cancers like colorectal, pancreatic, and ovarian cancer. |
| Infectious diseases (e.g., sepsis) | Soluble NCR3LG1 is elevated in sepsis and may modulate NK cell responses, contributing to immune dysfunction. | Clinical studies (e.g., PMID: 26712250) report increased sB7-H6 levels in sepsis patients, associated with severity and outcome. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tonsil | 0.0 | Not detected |
| Lymph node | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Bone marrow | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
| Brain | 0.0 | Not detected |
| Heart | 0.0 | Not detected |
| Testis | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | High | Constitutive expression; used as a model for NK cell recognition |
| HCT116 (colon cancer) | Moderate | Inducible expression under stress conditions |
| HeLa (cervical cancer) | Low | Expression can be upregulated by inflammatory cytokines |
| MCF7 (breast cancer) | Low | Expression varies; often low in hormone receptor-positive lines |
| A549 (lung cancer) | Moderate | Expression correlates with tumorigenicity |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (MAF <0.01%) | Potential loss of start codon, leading to truncated protein or loss of expression |
| c.250C>T (p.Arg84Trp) | Missense | Rare (MAF <0.01%) | May affect ligand-receptor interaction, altering NK cell activation |
| c.500_501insA (frameshift) | Insertion | Very rare | Predicted to cause premature stop codon, likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that abolish protein expression or disrupt binding to NCR3 (NKp30) would lead to loss of NK cell activation, potentially reducing immune surveillance of tumors.
Gain of Function (GOF)
Gain-of-function mutations are not well characterized; however, increased expression or enhanced binding affinity could enhance NK cell killing, which might be beneficial in cancer therapy but could also contribute to autoimmunity if misregulated.
Dominant Negative (DN)
No dominant-negative mutations have been reported for NCR3LG1. However, a truncated soluble form could act as a decoy, sequestering NKp30 and preventing membrane-bound NCR3LG1 from engaging, thereby inhibiting NK cell activation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Natural killer cell mediated cytotoxicity (KEGG hsa04650)
• Immune checkpoint signaling (custom pathway)
Protein Summary
NCR3LG1 is a type I transmembrane protein belonging to the B7 family. It consists of an extracellular immunoglobulin-like domain, a transmembrane region, and a short cytoplasmic tail. The protein is expressed on the surface of tumor cells and interacts with the NKp30 receptor on NK cells, triggering NK cell activation and cytotoxic response. Soluble forms of NCR3LG1, generated by proteolytic cleavage, can inhibit NK cell function by neutralizing NKp30. This protein is a promising target for cancer immunotherapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCR3LG1 Knockout HEK293 Cell Line | EDJ-KQ14397 | Human | 374383 | Details Get a Quote |
| NCR3LG1 Knockout A-549 Cell Line | EDJ-KQ44575 | Human | 374383 | Details Get a Quote |
| NCR3LG1 Knockout HCT 116 Cell Line | EDJ-KQ44576 | Human | 374383 | Details Get a Quote |
| NCR3LG1 Knockout HeLa Cell Line | EDJ-KQ43323 | Human | 374383 | Details Get a Quote |
