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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLITRK3
SLIT and NTRK like family member 3
Chromosome 3 · 3q26.1
NCBI Gene: 22865Ensembl: ENSG00000121871.5HGNC: HGNC:23501UniProt: O94933
22PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
postsynaptic specialization membraneprotein bindingGABA-ergic synapsesynaptic membrane adhesionIntellectual disabilitypolycythemia verapremature birthmyeloproliferative disorder
✦AI Summary

SLITRK3 is a transmembrane protein that suppresses neurite outgrowth and plays critical roles in synaptic development and neurological function. At the molecular level, SLITRK3 regulates inhibitory synapse assembly through trans-cellular interactions, particularly with ErbB4, facilitating postsynaptic specialization at GABAergic synapses 1. The protein is predominantly expressed in brain tissue with variable expression patterns across neural regions 2. Loss-of-function SLITRK3 variants cause epileptic encephalopathy characterized by seizures, intellectual disability, microcephaly, and developmental delay, with reduced parvalbumin-positive interneurons in knockout mice 3. SLITRK3 dysfunction impairs synaptic neurotransmission and peripheral/central nervous system development, positioning it as a key synaptic disease gene 3. Beyond neurological disorders, SLITRK3 shows dysregulation in various pathologies: upregulation in endometriosis-affected tissues 4, gastrointestinal stromal tumors where it predicts recurrence and metastasis 5, and triple-negative breast cancer as a tumor-infiltrating lymphocyte-related prognostic biomarker 6. SLITRK3 also associates with pain in Parkinson's disease through genetic variants affecting neurodevelopment 7, while reduced CSF levels correlate with unfavorable outcomes in VZV meningitis 8. These findings establish SLITRK3 as a multifunctional synaptic protein with broader implications in neuroinflammation and tumor biology.

Sources cited
1
SLITRK3 is a transmembrane postsynaptic protein at inhibitory synapses that interacts with ErbB4 to promote GABAergic synapse formation
PMID: 34226493
2
SLITRK3 is predominantly expressed in brain tissue and is differentially expressed in various brain tumors
PMID: 14557068
3
Loss-of-function SLITRK3 variants cause epileptic encephalopathy with seizures, intellectual disability, and reduced parvalbumin interneurons in knockout mice
PMID: 38495551
4
SLITRK3 is upregulated in endometriotic tissues
PMID: 41516028
5
SLITRK3 expression predicts gastrointestinal stromal tumor recurrence and metastasis
PMID: 26217092
6
SLITRK3 is a tumor-infiltrating lymphocyte-related hub gene associated with prognosis in triple-negative breast cancer
PMID: 39380273
7
SLITRK3 genetic variants associate with pain in early Parkinson's disease through neurodevelopmental mechanisms
PMID: 39979466
8
Reduced SLITRK3 levels in cerebrospinal fluid correlate with unfavorable outcomes in VZV meningitis
PMID: 37904697
Disease Associationsⓘ20
Intellectual disabilityOpen Targets
0.33Weak
polycythemia veraOpen Targets
0.21Weak
premature birthOpen Targets
0.17Weak
myeloproliferative disorderOpen Targets
0.15Weak
intracranial hemorrhageOpen Targets
0.07Suggestive
drug allergyOpen Targets
0.03Suggestive
placenta praeviaOpen Targets
0.03Suggestive
gastrointestinal stromal tumorOpen Targets
0.03Suggestive
Abruptio PlacentaeOpen Targets
0.03Suggestive
colon carcinomaOpen Targets
0.03Suggestive
gastrointestinal diseaseOpen Targets
0.03Suggestive
diaphragm diseaseOpen Targets
0.03Suggestive
intestinal diseaseOpen Targets
0.02Suggestive
vascular diseaseOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
neuropathyOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
childhood supratentorial ependymomaOpen Targets
0.02Suggestive
ependymomaOpen Targets
0.02Suggestive
Abnormality of the gastrointestinal tractOpen Targets
0.02Suggestive
Pathogenic Variants1
NM_001318810.2(SLITRK3):c.1816G>T (p.Glu606Ter)Pathogenic
Intellectual disability
☆☆☆☆2019→ Residue 606
View on ClinVar ↗
Related Genes
NLGN2Protein interaction81%SLITRK2Shared pathway80%SLITRK5Shared pathway75%LRRC4BShared pathway60%IL1RAPL1Protein interaction57%SLITRK1Shared pathway57%
Tissue Expression6 tissues
Liver
100%
Brain
93%
Ovary
3%
Lung
2%
Bone Marrow
1%
Heart
0%
Gene Interaction Network
Click a node to explore
SLITRK3NLGN2SLITRK2SLITRK5LRRC4BIL1RAPL1SLITRK1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O94933
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.36Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.24 [0.16–0.36]
RankingsWhere SLITRK3 stands among ~20K protein-coding genes
  • #13,744of 20,598
    Most Researched22
  • #5,350of 5,498
    Most Pathogenic Variants1
  • #1,654of 17,882
    Most Constrained (LOEUF)0.36 · top 10%
Genes detectedSLITRK3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Endometriosis: From Genes to Global Burden.
PMID: 41516028
Int J Mol Sci · 2025
1.00
2
SLITRK3 expression correlation to gastrointestinal stromal tumor risk rating and prognosis.
PMID: 26217092
World J Gastroenterol · 2015
0.90
3
Exploring the early drivers of pain in Parkinson's disease.
PMID: 39979466
Sci Rep · 2025
0.80
4
Human mutations in
PMID: 38495551
Front Mol Neurosci · 2024
0.70
5
Identification of an immune cell infiltration-related gene signature for prognosis prediction in triple-negative breast cancer.
PMID: 39380273
Cell Mol Biol (Noisy-le-grand) · 2024
0.60