NRP2 Gene: Neuropilin 2 - Function, Disease Associations, and Expression
Comprehensive biomedical overview of NRP2, including genomic context, protein function, expression profiles, and clinical significance.
Gene Information Card
| Symbol | NRP2 |
|---|---|
| Full Name | Neuropilin 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q33.3 (GRCh38) |
| NCBI Gene ID | 8828 ncbi.nlm.nih.gov/gene/8828 |
| Ensembl ID | ENSG00000118257 |
| UniProt ID | O60462 |
| OMIM ID | 602070 |
| HGNC ID | 8005 |
| Aliases | NP2, NPN2, VEGF165R2, PRO2714 |
Description
NRP2 encodes neuropilin 2, a transmembrane glycoprotein that functions as a receptor for class 3 semaphorins and certain vascular endothelial growth factor (VEGF) isoforms. It plays critical roles in neuronal guidance, angiogenesis, and immune regulation. Alternative splicing generates multiple isoforms with distinct functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (e.g., breast, lung, colorectal) | Overexpression promotes tumor angiogenesis and metastasis via VEGF and semaphorin signaling. | COSMIC: frequent overexpression in various tumors; ClinVar: somatic variants reported. |
| Lymphatic malformations | Mutations affecting NRP2 function disrupt lymphatic vessel development. | OMIM: 602070; ClinVar: rare variants associated. |
| Cardiovascular defects | Impaired NRP2 signaling leads to abnormal heart and vascular development. | Mouse models; OMIM: 602070. |
| Neurodevelopmental disorders | Altered semaphorin signaling affects axon guidance, potentially contributing to cognitive deficits. | OMIM: 602070; literature evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Heart | 8.4 | Low |
| Brain | 6.1 | Low |
| Liver | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 15.0 | High expression; relevant to angiogenesis. |
| MCF7 (breast cancer) | 8.5 | Moderate; associated with tumor progression. |
| A549 (lung cancer) | 7.2 | Moderate; potential role in metastasis. |
| HEK293 (embryonic kidney) | 5.0 | Low baseline; used for recombinant studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.01% (gnomAD) | May affect ligand binding; clinical significance uncertain. |
| c.1567C>T (p.Arg523Ter) | Nonsense | Rare | Loss of function; associated with lymphatic anomalies. |
| c.2101_2102insA (frameshift) | Insertion | Somatic (COSMIC) | Loss of function in tumors; potential driver. |
| c.789G>C (p.Glu263Asp) | Missense | Somatic (COSMIC) | Gain of function; increased VEGF signaling. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) impair NRP2-mediated signaling, leading to defective lymphatic development and potentially contributing to tumor suppression in some contexts.
Gain of Function (GOF)
Gain-of-function mutations (e.g., specific missense) enhance VEGF/semaphorin binding, promoting angiogenesis and tumor progression.
Dominant Negative (DN)
Dominant-negative effects have been proposed for certain missense variants that disrupt dimerization, interfering with wild-type NRP2 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• VEGF signaling pathway (Reactome: R-HSA-194138)
• Semaphorin interactions (Reactome: R-HSA-373755)
• Axon guidance (KEGG: hsa04360)
• Development of lymphatic vasculature (Reactome: R-HSA-2143220)
Protein Summary
Neuropilin 2 (NRP2) is a 931-amino-acid type I transmembrane protein with a large extracellular region containing CUB domains, coagulation factor V/VIII homology domains, and MAM domains. It lacks intrinsic enzymatic activity but serves as a co-receptor for class 3 semaphorins (with plexins) and for VEGF ligands (with VEGF receptors). NRP2 is essential for the development of lymphatic vessels, axon guidance, and angiogenesis. Its expression is upregulated in various cancers, where it promotes tumor vascularization and metastasis. Alternative splicing produces soluble isoforms that can modulate signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NRP2 Knockout HEK293 Cell Line | EDJ-KQ6377 | Human | 8828 | Details Get a Quote |
| NRP2 Knockout A-549 Cell Line | EDJ-KQ30374 | Human | 8828 | Details Get a Quote |
| NRP2 Knockout HeLa Cell Line | EDJ-KQ30375 | Human | 8828 | Details Get a Quote |
| NRP2 Knockout HCT 116 Cell Line | EDJ-KQ71966 | Human | 8828 | Details Get a Quote |
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