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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ROBO1
roundabout guidance receptor 1
Chromosome 3 Β· 3p12.3
NCBI Gene: 6091Ensembl: ENSG00000169855.21HGNC: HGNC:10249UniProt: Q1RMC8
200PubMed Papers
23Diseases
0Drugs
44Pathogenic Variants
FUNCTIONAL ROLE
Receptor
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingaxon guidance receptor activityLRR domain bindingidentical protein bindingneurooculorenal syndromepituitary hormone deficiency, combined or isolated, 8pituitary stalk interruption syndromecongenital anomaly of kidney and urinary tract
✦AI Summary

ROBO1 is a transmembrane guidance receptor that mediates cellular migration and axonal navigation through binding of SLIT ligands 1. In its canonical role, ROBO1 acts as a receptor for SLIT1 and SLIT2, regulating axonal guidance during neural development and participating in chemorepulsion at the ventral midline 2. Beyond neurodevelopment, SLIT2-ROBO1 signaling has emerged as a critical regulator in multiple pathological processes. In liver disease, elevated SLIT2-ROBO1 signaling promotes hepatic stellate cell activation and fibrosis through phosphorylation of Smad2/3 and PI3K/AKT pathways 1, while also driving intrahepatic angiogenesis during chr3 liver injury 3. In cancer, endothelial ROBO1 promotes tumor metastasis by facilitating cancer cell intravasation 2, and tumor-derived SLIT2 activates macrophages and microglia via ROBO1/2-mediated PI3K-Ξ³ signaling to establish immunosuppression in glioblastoma 4. In glioblastoma specifically, ROBO1 expression inversely correlates with radiation-induced migration 5, and ROBO1 serves as a dependency in recurrent tumors amenable to CAR T cell targeting 6. ROBO1 blockade reduces pathological ocular neovascularization by targeting myeloid cell populations 7. These findings establish ROBO1 as a multifunctional receptor with therapeutic potential across fibrotic, neoplastic, and vascular diseases.

Sources cited
1
SLIT2-ROBO1 signaling activates hepatic stellate cells and promotes liver fibrosis through Smad2/3 and PI3K/AKT phosphorylation
PMID: 26264936
2
Endothelial-derived SLIT2-ROBO1 promotes cancer cell migration and intravasation in breast and lung cancer metastasis
PMID: 32999457
3
Tumor-derived SLIT2 activates macrophages and microglia via ROBO1/2-mediated PI3K-Ξ³ to establish glioblastoma immunosuppression
PMID: 34181595
4
ROBO1 overexpression decreases glioblastoma cell motility and inhibits radiation-induced migration through vimentin regulation
PMID: 29864155
5
ROBO1 represents a functional dependency in recurrent glioblastoma exploitable by ROBO1-targeted CAR T cell therapy
PMID: 39095594
6
ROBO1/2 blockade reduces ocular neovascularization through inhibition of myeloid cell activation and improved vascular function
PMID: 39565875
7
SLIT2-ROBO1 signaling from ductular reaction cells promotes intrahepatic angiogenesis during chronic liver disease
PMID: 34490644
8
ROBO1 identified as candidate disease gene in genetic disease screening studies
PMID: 28600779
Disease Associationsβ“˜23
neurooculorenal syndromeOpen Targets
0.66Moderate
pituitary hormone deficiency, combined or isolated, 8Open Targets
0.56Moderate
pituitary stalk interruption syndromeOpen Targets
0.55Moderate
congenital anomaly of kidney and urinary tractOpen Targets
0.52Moderate
congenital hydronephrosisOpen Targets
0.52Moderate
nystagmus, congenital, autosomal recessiveOpen Targets
0.43Moderate
Intellectual disabilityOpen Targets
0.41Moderate
placenta praeviaOpen Targets
0.38Weak
Short statureOpen Targets
0.36Weak
alcohol drinkingOpen Targets
0.35Weak
Tetralogy of FallotOpen Targets
0.34Weak
bilateral renal agenesisOpen Targets
0.33Weak
congenital heart diseaseOpen Targets
0.33Weak
migraine with auraOpen Targets
0.32Weak
Abnormal heart morphologyOpen Targets
0.32Weak
placental retentionOpen Targets
0.31Weak
diverticular diseaseOpen Targets
0.31Weak
macular degenerationOpen Targets
0.29Weak
premature birthOpen Targets
0.29Weak
deep vein thrombosisOpen Targets
0.28Weak
Neurooculorenal syndromeUniProt
Nystagmus 8, congenital, autosomal recessiveUniProt
Pituitary hormone deficiency, combined or isolated, 8UniProt
Pathogenic Variants44
NM_002941.4(ROBO1):c.856C>T (p.Arg286Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 286
NM_002941.4(ROBO1):c.928C>T (p.Arg310Ter)Pathogenic
Tetralogy of Fallot|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 310
NM_002941.4(ROBO1):c.1537C>T (p.Arg513Ter)Likely pathogenic
Neurooculorenal syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 513
NM_002941.4(ROBO1):c.1198C>T (p.Gln400Ter)Pathogenic
Congenital anomaly of kidney and urinary tract|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 400
NM_002941.4(ROBO1):c.769_772del (p.Thr257fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 257
NM_002941.4(ROBO1):c.355C>T (p.Arg119Ter)Likely pathogenic
Tetralogy of Fallot|Neurooculorenal syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 119
NM_002941.4(ROBO1):c.1501C>T (p.Arg501Ter)Likely pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 501
NM_002941.4(ROBO1):c.2929del (p.Ala977fs)Pathogenic
Pituitary stalk interruption syndrome
β˜…β˜…β˜†β˜†2021β†’ Residue 977
NM_002941.4(ROBO1):c.3450C>A (p.Tyr1150Ter)Pathogenic
Pituitary stalk interruption syndrome
β˜…β˜…β˜†β˜†2021β†’ Residue 1150
NM_002941.4(ROBO1):c.3379C>T (p.Arg1127Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1127
NM_002941.4(ROBO1):c.3952del (p.Leu1318fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1318
NM_002941.4(ROBO1):c.2320+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_002941.4(ROBO1):c.4282+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_002941.4(ROBO1):c.583C>T (p.Arg195Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 195
NM_002941.4(ROBO1):c.661C>T (p.Arg221Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 221
NM_002941.4(ROBO1):c.1170+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_002941.4(ROBO1):c.4478del (p.Pro1493fs)Likely pathogenic
Neurooculorenal syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 1493
NM_002941.4(ROBO1):c.1343-1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_002941.4(ROBO1):c.554_555dup (p.Pro186fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 186
NM_002941.4(ROBO1):c.917+2T>CLikely pathogenic
not provided|Colon adenocarcinoma
β˜…β˜†β˜†β˜†2024
View on ClinVar β†—
Related Genes
ENAHProtein interaction100%ROBO4Protein interaction99%DCDC2Protein interaction98%KIAA0319Protein interaction97%NRP1Protein interaction93%PAK4Protein interaction92%
Tissue Expression6 tissues
Ovary
100%
Heart
85%
Brain
77%
Lung
45%
Liver
18%
Bone Marrow
8%
Gene Interaction Network
Click a node to explore
ROBO1ENAHROBO4DCDC2KIAA0319NRP1PAK4
PROTEIN STRUCTURE
Preparing viewer…
PDB2V9T Β· 1.70 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.86LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.64–0.86]
RankingsWhere ROBO1 stands among ~20K protein-coding genes
  • #2,114of 20,598
    Most Researched200 Β· top quartile
  • #1,437of 5,498
    Most Pathogenic Variants44
  • #7,460of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedROBO1
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
Activation of Slit2-Robo1 signaling promotes liver fibrosis.
PMID: 26264936
J Hepatol Β· 2015
1.00
2
Tumoural activation of TLR3-SLIT2 axis in endothelium drives metastasis.
PMID: 32999457
Nature Β· 2020
0.90
3
SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia.
PMID: 34181595
J Clin Invest Β· 2021
0.80
4
Cancer associated fibroblast derived SLIT2 drives gastric cancer cell metastasis by activating NEK9.
PMID: 37443302
Cell Death Dis Β· 2023
0.72
5
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet Β· 2017
0.70