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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLIT1
slit guidance ligand 1
Chromosome 10 · 10q24.1
NCBI Gene: 6585Ensembl: ENSG00000187122.17HGNC: HGNC:11085UniProt: A6H8V1
34PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative chemotaxisaxon guidancemotor neuron axon guidancechemorepulsion involved in embryonic olfactory bulb interneuron precursor migrationpsoriatic arthritisneurodegenerative diseaseulcerative colitisMonomelic amyotrophy
✦AI Summary

SLIT1 encodes a secreted glycoprotein that functions as a molecular guidance cue in cellular migration and axonal navigation during neural development 1. The protein contains leucine-rich repeats, EGF repeats, and a laminin G-like domain, and can be proteolytically cleaved to generate functional fragments with different activities 1. SLIT1 mediates its effects through binding to Roundabout (ROBO) receptors, particularly ROBO2, activating downstream signaling cascades including RhoA pathway modulation 2. Under hypoxic conditions, neuronal SLIT1 expression provides a compensatory mechanism to rescue oligodendrocyte differentiation and myelination through the Slit1-Robo2-srGAP1-RhoA signaling axis 2. In cancer contexts, SLIT1 exhibits tumor suppressor properties, with frequent promoter hypermethylation leading to transcriptional silencing in various cancers including gliomas 3. However, SLIT1 can also promote cancer progression in specific contexts, as lactate-induced histone modifications activate SLIT1 transcription to drive perineural invasion in pancreatic cancer 4. The gene shows tissue-specific expression patterns and methylation status that correlate with clinical outcomes, making it both a potential therapeutic target and prognostic marker 56.

Sources cited
1
SLIT1 is a secreted glycoprotein with specific structural domains that functions in axonal guidance
PMID: 18269211
2
SLIT1 rescues oligodendrocyte differentiation under hypoxic conditions through ROBO2-RhoA signaling
PMID: 40117292
3
SLIT1 undergoes promoter hypermethylation and acts as a tumor suppressor in gliomas
PMID: 15534609
4
SLIT1 expression is activated by lactate-induced histone modifications to promote perineural invasion
PMID: 40138590
5
SLIT1 serves as a prognostic marker and potential therapeutic target in prostate cancer
PMID: 40508075
6
SLIT1 affects glioma radiosensitivity through Wnt/β-catenin pathway regulation
PMID: 35996510
Disease Associationsⓘ20
psoriatic arthritisOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.29Weak
ulcerative colitisOpen Targets
0.27Weak
Monomelic amyotrophyOpen Targets
0.26Weak
arthritisOpen Targets
0.24Weak
type 2 diabetes mellitusOpen Targets
0.20Weak
risk-taking behaviourOpen Targets
0.17Weak
Abnormality of the skeletal systemOpen Targets
0.16Weak
gliomaOpen Targets
0.08Suggestive
glioblastomaOpen Targets
0.07Suggestive
intelligenceOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.04Suggestive
intellectual developmental disorder, X-linked 110Open Targets
0.04Suggestive
papillary thyroid carcinomaOpen Targets
0.03Suggestive
diabetes mellitusOpen Targets
0.03Suggestive
ataxia telangiectasiaOpen Targets
0.03Suggestive
Parkinson diseaseOpen Targets
0.03Suggestive
attention deficit hyperactivity disorderOpen Targets
0.02Suggestive
major depressive disorderOpen Targets
0.02Suggestive
Pituitary prolactin cell adenomaOpen Targets
0.02Suggestive
Pathogenic Variants1
NM_003061.3(SLIT1):c.2276T>A (p.Ile759Asn)Likely pathogenic
Monomelic amyotrophy
☆☆☆☆→ Residue 759
View on ClinVar ↗
Related Genes
ROBO4Protein interaction99%ROBO3Protein interaction87%SRGAP1Protein interaction84%DCCProtein interaction81%ROBO1Protein interaction81%ROBO2Protein interaction81%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
12%
Ovary
2%
Heart
2%
Liver
2%
Lung
2%
Gene Interaction Network
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SLIT1ROBO4ROBO3SRGAP1DCCROBO1ROBO2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O75093
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.43Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.35 [0.28–0.43]
RankingsWhere SLIT1 stands among ~20K protein-coding genes
  • #11,245of 20,598
    Most Researched34
  • #5,231of 5,498
    Most Pathogenic Variants1
  • #2,323of 17,882
    Most Constrained (LOEUF)0.43 · top quartile
Genes detectedSLIT1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer.
PMID: 40138590
Cancer Res · 2025
1.00
2
A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions.
PMID: 40117292
Cell Rep · 2025
0.90
3
Slits and their receptors.
PMID: 18269211
Adv Exp Med Biol · 2007
0.80
4
The SLIT/ROBO Pathway in Liver Fibrosis and Cancer.
PMID: 37238655
Biomolecules · 2023
0.70
5
Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes.
PMID: 27082735
Int J Oncol · 2016
0.60