NTN1 Gene: Netrin-1, Axon Guidance and Cancer Signaling
Comprehensive genomic and functional overview of NTN1 (Netrin-1), a secreted axon guidance molecule implicated in neurodevelopment and tumorigenesis.
Gene Information Card
| Symbol | NTN1 |
|---|---|
| Full Name | Netrin 1 |
| Gene Type | protein coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 9423 ncbi.nlm.nih.gov/gene/9423 |
| Ensembl ID | ENSG00000165304 |
| UniProt ID | O95631 |
| OMIM ID | 601614 |
| HGNC ID | 8029 |
| Aliases | NTN1L, netrin-1, NTN1 |
Description
NTN1 encodes netrin-1, a secreted laminin-related protein that functions as a bifunctional axon guidance cue. It acts as a chemoattractant for commissural axons via DCC (deleted in colorectal cancer) receptors and as a chemorepellent for specific neurons via UNC5 receptors. Netrin-1 also plays roles in cell migration, angiogenesis, and tissue morphogenesis. In cancer, NTN1 overexpression can suppress apoptosis by inhibiting DCC/UNC5-mediated programmed cell death, contributing to tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | NTN1 overexpression inhibits DCC/UNC5-mediated apoptosis, promoting tumor survival and progression. | COSMIC; multiple studies (e.g., Mazelin et al., 2004) |
| Breast Cancer | NTN1 promotes tumor growth and metastasis through activation of UNC5B and downstream signaling. | COSMIC; studies (e.g., Fitamant et al., 2008) |
| Neuroblastoma | NTN1 expression correlates with poor prognosis and promotes tumor cell survival. | COSMIC; studies (e.g., Delloye-Bourgeois et al., 2009) |
| Congenital Mirror Movements | Mutations in NTN1 are associated with abnormal axon guidance leading to mirror movements. | ClinVar; OMIM 601614; studies (e.g., Srour et al., 2010) |
| Neural Tube Defects | NTN1 variants may contribute to defective neural tube closure. | ClinVar; studies (e.g., Li et al., 2017) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal Cord | 8.9 | Low |
| Heart | 3.2 | Low |
| Liver | 0.8 | Not detected |
| Kidney | 4.1 | Low |
| Lung | 2.5 | Low |
| Colon | 1.8 | Low |
| Breast | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used in neurodifferentiation studies |
| MCF7 (breast cancer) | 2.1 | Low expression |
| HCT116 (colorectal cancer) | 8.7 | Moderate expression; relevant to cancer studies |
| HEK293 (embryonic kidney) | 1.0 | Low expression; commonly used for recombinant protein production |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.214C>T (p.Arg72Cys) | Missense | Rare (MAF <0.01) | Associated with congenital mirror movements; disrupts netrin-1 function |
| c.620G>A (p.Arg207His) | Missense | Rare | Reported in neural tube defects; potential loss of function |
| c.1021A>G (p.Thr341Ala) | Missense | Rare | Uncertain significance; possibly benign |
| c.1255C>T (p.Arg419Trp) | Missense | Rare | Reported in cancer; may affect receptor binding |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NTN1 impair axon guidance and can lead to congenital mirror movements or neural tube defects.
Gain of Function (GOF)
Gain-of-function (overexpression) is common in cancers, leading to increased netrin-1 levels that inhibit apoptosis and promote tumor progression.
Dominant Negative (DN)
Dominant-negative effects have been suggested for some missense mutations that disrupt netrin-1 dimerization or receptor interaction, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • axon guidance | • chemoattractant activity |
| • chemokine activity | • extracellular matrix organization |
| • cell adhesion | • positive regulation of cell migration |
| • negative regulation of apoptotic process | • netrin receptor binding |
| • signal transduction |
Pathways
• Axon guidance (KEGG: hsa04360)
• Netrin signaling (Reactome: R-HSA-373752)
• DCC-mediated attractive signaling (Reactome: R-HSA-373755)
• UNC5-mediated repulsive signaling (Reactome: R-HSA-373756)
Protein Summary
Netrin-1 is a secreted protein of approximately 75 kDa, composed of a laminin VI domain, a V domain, and three EGF-like repeats. It forms homodimers and binds to receptors DCC, UNC5A-D, and neogenin. Netrin-1 is crucial for neuronal guidance, but also regulates cell survival: when bound to DCC/UNC5, it prevents apoptosis. In cancer, netrin-1 overexpression blocks the pro-apoptotic activity of these receptors, thereby promoting tumor growth. The protein is also involved in angiogenesis and tissue morphogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NTN1 Knockout HEK293 Cell Line | EDJ-KQ17772 | Human | 9423 | Details Get a Quote |
| NTN1 Knockout HCT 116 Cell Line | EDJ-KQ19849 | Human | 9423 | Details Get a Quote |
| NTN1 Knockout HeLa Cell Line | EDJ-KQ55161 | Human | 9423 | Details Get a Quote |
| NTN1 Knockout A-549 Cell Line | EDJ-KQ63641 | Human | 9423 | Details Get a Quote |
