SLIT3: A Key Axon Guidance Molecule and Its Role in Development and Disease
Comprehensive gene card for SLIT3, including genomic information, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | SLIT3 |
|---|---|
| Full Name | slit guidance ligand 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 6586 ncbi.nlm.nih.gov/gene/6586 |
| Ensembl ID | ENSG00000184347 |
| UniProt ID | O75094 |
| OMIM ID | 603745 |
| HGNC ID | 11027 |
| Aliases | SLIT2-like, MEGF5, SLIL3, slit homolog 3 |
Description
SLIT3 encodes a secreted glycoprotein that belongs to the slit family of axon guidance molecules. It functions as a ligand for Roundabout (ROBO) receptors, mediating repulsive cues during neuronal development. Beyond the nervous system, SLIT3 is involved in cell migration, angiogenesis, and organogenesis. Its dysregulation is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | SLIT3 promoter hypermethylation leads to reduced expression, potentially promoting tumor invasion and metastasis. | ClinVar, COSMIC |
| Colorectal Cancer | Loss of SLIT3 expression via methylation is associated with poor prognosis and increased metastatic potential. | NCBI Gene, COSMIC |
| Prostate Cancer | SLIT3 downregulation correlates with aggressive tumor features and may influence ROBO signaling. | COSMIC |
| Developmental Defects (e.g., cleft palate) | SLIT3 mutations disrupt axon guidance and craniofacial development, as observed in animal models. | OMIM |
| Diabetic Nephropathy | SLIT3 is involved in podocyte function and glomerular filtration; altered expression contributes to kidney fibrosis. | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Brain | 10.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.5 | Embryonic kidney cells; high expression |
| A549 | 14.2 | Lung carcinoma; moderate expression |
| MCF7 | 6.8 | Breast cancer; low expression |
| HepG2 | 3.2 | Liver cancer; very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Premature truncation; loss of function |
| c.567G>A (p.Gly189Arg) | Missense | 0.2% | Altered receptor binding; potential dominant-negative effect |
| Promoter methylation | Epigenetic | Variable | Silencing of SLIT3 expression in tumors |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg412*) and promoter methylation lead to reduced or absent SLIT3 protein, impairing axon guidance and promoting tumor invasion.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in SLIT3.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly189Arg) may produce a defective protein that interferes with wild-type SLIT3 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • axon guidance | • cell migration |
| • chemorepulsion | • signal transduction |
| • extracellular matrix organization | • angiogenesis |
Pathways
• ROBO receptor signaling
• axon guidance
• cell adhesion molecules (CAMs)
• signaling by SLIT-ROBO
Protein Summary
SLIT3 is a secreted, ~170 kDa glycoprotein that forms homodimers. It contains multiple leucine-rich repeats (LRRs) and epidermal growth factor (EGF)-like domains. The protein binds to ROBO1 and ROBO2 receptors, initiating a signaling cascade that repels migrating neurons and endothelial cells. SLIT3 is also involved in branching morphogenesis and tissue patterning.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLIT3 Knockout HEK293 Cell Line | EDJ-KQ5802 | Human | 6586 | Details Get a Quote |
| SLIT3 Knockout A-549 Cell Line | EDJ-KQ29215 | Human | 6586 | Details Get a Quote |
| SLIT3 Knockout HeLa Cell Line | EDJ-KQ54522 | Human | 6586 | Details Get a Quote |
| SLIT3 Knockout HCT 116 Cell Line | EDJ-KQ71479 | Human | 6586 | Details Get a Quote |
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