NECTIN2 (CD112): A Key Immune Checkpoint and Viral Entry Receptor
Comprehensive gene overview of NECTIN2, its role in cancer immunity, viral infection, and genetic disease.
Gene Information Card
| Symbol | NECTIN2 |
|---|---|
| Full Name | nectin cell adhesion molecule 2 |
| Gene Type | protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 5819 ncbi.nlm.nih.gov/gene/5819 |
| Ensembl ID | ENSG00000130202 |
| UniProt ID | Q92692 |
| OMIM ID | 600798 |
| HGNC ID | 9706 |
| Aliases | CD112, PVRL2, PRR2, HVEB, Nectin-2 |
Description
NECTIN2 (also known as CD112 or PVRL2) encodes a type I transmembrane glycoprotein belonging to the nectin family of cell adhesion molecules. It is widely expressed in various tissues and functions as a Ca2+-independent immunoglobulin-like cell adhesion molecule. NECTIN2 plays critical roles in cell-cell adhesion, immune regulation, and viral entry. It serves as a ligand for multiple immune receptors, including DNAM-1 (CD226), TIGIT, and CD112R (PVRIG), thereby modulating T cell and NK cell responses. Additionally, NECTIN2 acts as an entry receptor for certain herpesviruses, including herpes simplex virus (HSV) and pseudorabies virus. Alterations in NECTIN2 expression have been implicated in cancer progression, autoimmune diseases, and Alzheimer's disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | NECTIN2 overexpression on tumor cells suppresses anti-tumor immunity via engagement with TIGIT and CD112R on immune cells, leading to T cell and NK cell exhaustion. It also promotes tumor cell adhesion and invasion. | Multiple studies, including TCGA data and functional assays, show elevated NECTIN2 expression in many solid tumors and hematologic malignancies, correlating with poor prognosis. |
| Herpes simplex virus infection | NECTIN2 serves as an entry receptor for HSV-1 and HSV-2, mediating viral entry into host cells via interaction with viral glycoprotein D (gD). | In vitro and in vivo studies confirm NECTIN2's role as a receptor for HSV entry. |
| Alzheimer's disease | Genetic variants in NECTIN2 have been associated with Alzheimer's disease risk, possibly through effects on amyloid-beta metabolism or neuroinflammation. | GWAS studies have identified NECTIN2 as a susceptibility locus for late-onset Alzheimer's disease. |
| Autoimmune diseases | Altered NECTIN2 expression may contribute to dysregulated immune responses, but specific mechanisms are less defined. | Preliminary studies suggest associations with conditions like multiple sclerosis and rheumatoid arthritis, but further validation is needed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Spleen | 15.2 | Medium |
| Bone Marrow | 10.4 | Medium |
| Skin | 7.8 | Low |
| Small Intestine | 11.3 | Medium |
| Colon | 9.9 | Low |
| Ovary | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 18.5 | High expression |
| A549 (lung carcinoma) | 12.3 | Moderate expression |
| MCF7 (breast carcinoma) | 9.8 | Low expression |
| HepG2 (hepatocellular carcinoma) | 7.2 | Low expression |
| SH-SY5Y (neuroblastoma) | 14.6 | Moderate expression |
| Jurkat (T cell leukemia) | 22.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.485C>T (p.Pro162Leu) | Missense | Rare (MAF <0.01) | Potential impact on protein stability or ligand binding; clinical significance uncertain. |
| c.739G>A (p.Val247Ile) | Missense | Rare (MAF <0.01) | May affect glycosylation or receptor interaction; not well characterized. |
| c.1123A>G (p.Thr375Ala) | Missense | Rare (MAF <0.01) | Located in cytoplasmic domain; possible effect on signaling. |
| c.1265C>T (p.Pro422Leu) | Missense | Rare (MAF <0.01) | Potential impact on protein function; no known disease association. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NECTIN2 are not well documented. However, complete knockout in mice leads to impaired immune responses and reduced viral entry, but no major developmental defects.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported. Overexpression of wild-type NECTIN2 in tumors is a common mechanism to evade immune surveillance.
Dominant Negative (DN)
No dominant-negative mutations have been described for NECTIN2.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion | • cell-cell adhesion |
| • immune response | • negative regulation of T cell activation |
| • positive regulation of natural killer cell activation | • viral entry into host cell |
| • protein homodimerization activity | • protein heterodimerization activity |
| • identical protein binding | • signaling receptor binding |
Pathways
• Cell adhesion molecules (CAMs)
• Natural killer cell mediated cytotoxicity
• T cell receptor signaling pathway
• Herpes simplex infection
• Immune checkpoint regulation
Protein Summary
NECTIN2 is a 538-amino acid type I membrane protein with an extracellular region containing three immunoglobulin-like domains (V, C2, and C2), a transmembrane domain, and a cytoplasmic tail with a PDZ-binding motif. It forms homodimers and heterodimers with other nectins. As a ligand for DNAM-1, TIGIT, and CD112R, it regulates immune cell functions. In cancer, NECTIN2 overexpression contributes to immune evasion. It also serves as an entry receptor for herpesviruses. The protein is glycosylated and undergoes proteolytic cleavage in some contexts.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NECTIN2 Knockout HEK293 Cell Line | EDJ-KQ5614 | Human | 5819 | Details Get a Quote |
| NECTIN2 Knockout A-549 Cell Line | EDJ-KQ28910 | Human | 5819 | Details Get a Quote |
| NECTIN2 Knockout HCT 116 Cell Line | EDJ-KQ28911 | Human | 5819 | Details Get a Quote |
| NECTIN2 Knockout HeLa Cell Line | EDJ-KQ28912 | Human | 5819 | Details Get a Quote |
