ROBO4: Roundabout Guidance Receptor 4
Endothelial-specific axon guidance receptor involved in angiogenesis and vascular development
Gene Information Card
| Symbol | ROBO4 |
|---|---|
| Full Name | Roundabout Guidance Receptor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q24.2 |
| NCBI Gene ID | 54538 ncbi.nlm.nih.gov/gene/54538 |
| Ensembl ID | ENSG00000154133 |
| UniProt ID | Q8WZ75 |
| OMIM ID | 607528 |
| HGNC ID | 17985 |
| Aliases | MRB, magic roundabout, roundabout homolog 4 |
Description
ROBO4 (Roundabout Guidance Receptor 4) is a member of the roundabout (ROBO) family of axon guidance receptors. It is specifically expressed in endothelial cells and plays a critical role in angiogenesis, vascular development, and endothelial cell migration. ROBO4 mediates repulsive signals in response to Slit ligands, regulating blood vessel formation and vascular permeability. It is also implicated in tumor angiogenesis and various vascular pathologies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (angiogenesis-dependent) | ROBO4 overexpression in tumor endothelium promotes aberrant angiogenesis via Slit2 signaling | PMID: 16959974 |
| Diabetic retinopathy | Altered ROBO4 expression contributes to retinal neovascularization | PMID: 20086235 |
| Vascular malformations | Loss-of-function mutations in ROBO4 disrupt endothelial cell guidance leading to vascular defects | PMID: 26005864 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Kidney | 9.8 | Medium |
| Heart | 8.2 | Medium |
| Brain | 3.1 | Low |
| Liver | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 15.3 | High expression |
| HMEC-1 (microvascular endothelial) | 14.7 | High expression |
| HEK 293 | 1.2 | Very low expression |
| HeLa | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; truncated protein |
| c.567G>A (p.Trp189*) | Nonsense | <0.1% | Loss of function; premature stop |
| c.890A>G (p.Tyr297Cys) | Missense | <0.1% | Unknown; predicted damaging |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (p.Arg412*, p.Trp189*) result in truncated, non-functional ROBO4 protein, impairing endothelial cell guidance and angiogenesis.
Gain of Function (GOF)
No gain-of-function mutations reported in ROBO4.
Dominant Negative (DN)
No dominant-negative mutations reported in ROBO4.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion (GO:0007155) | • axon guidance (GO:0007411) |
| • angiogenesis (GO:0001525) | • positive regulation of GTPase activity (GO:0043547) |
| • plasma membrane (GO:0005886) |
Pathways
• Slit/Robo signaling pathway
• Angiogenesis (VEGF signaling)
• Axon guidance
Protein Summary
ROBO4 is a transmembrane receptor of the immunoglobulin superfamily, containing five immunoglobulin-like domains and three fibronectin type III repeats in the extracellular region, and a conserved cytoplasmic domain with CC motifs. It binds Slit ligands (Slit2) to mediate repulsive guidance cues in endothelial cells. ROBO4 is essential for proper vascular patterning and barrier function. Its expression is largely restricted to endothelial cells, making it a potential target for anti-angiogenic therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ROBO4 Knockout HEK293 Cell Line | EDJ-KQ11456 | Human | 54538 | Details Get a Quote |
| ROBO4 Knockout HeLa Cell Line | EDJ-KQ56432 | Human | 54538 | Details Get a Quote |
| ROBO4 Knockout A-549 Cell Line | EDJ-KQ64927 | Human | 54538 | Details Get a Quote |
| ROBO4 Knockout HCT 116 Cell Line | EDJ-KQ73369 | Human | 54538 | Details Get a Quote |
