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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLITRK5
SLIT and NTRK like family member 5
Chromosome 13 · 13q31.2
NCBI Gene: 26050Ensembl: ENSG00000165300.9HGNC: HGNC:20295UniProt: O94991
41PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
signaling receptor complexsynaptic membrane adhesionprotein bindingpositive regulation of synapse assemblyautism spectrum disorderfrozen shoulderdiabetes mellituspreeclampsia
✦AI Summary

SLITRK5 (SLIT and NTRK like family member 5) is a transmembrane protein widely expressed in the central nervous system that functions as a key regulator of synaptic development and signaling. The protein contains leucine-rich repeats (LRRs) in its extracellular domain and tyrosine residues in its intracellular domain, enabling diverse regulatory functions 1. SLITRK5 promotes inhibitory synapse formation on dopamine neurons while suppressing neurite outgrowth, with its loss leading to excessive grooming behaviors reminiscent of obsessive-compulsive disorder in mouse models 2 3. The protein acts as a negative regulator of hedgehog signaling in osteoblasts by binding hedgehog ligands and interacting with PTCH1, thereby controlling bone formation 4. SLITRK5 is implicated in various neuropsychiatric conditions, with upregulation observed in epilepsy patients and animal models 5 and dysregulation noted in Friedreich ataxia 6. However, genetic association studies have not found evidence linking SLITRK5 variants to Tourette syndrome 7. The protein's role in synaptic adhesion, neuron differentiation, and synaptogenesis positions it as a potential therapeutic target for central nervous system disorders characterized by synaptic dysfunction.

Sources cited
1
SLITRK5 structure contains LRRs and tyrosine residues, and regulates CNS development
PMID: 35872846
2
SLITRK5 promotes inhibitory synapses on dopamine neurons and controls hyperactivity behavior
PMID: 32075770
3
SLITRK5 knockout mice show excessive grooming behaviors resembling OCD
PMID: 21386675
4
SLITRK5 negatively regulates hedgehog signaling in osteoblasts
PMID: 34326333
5
SLITRK5 is upregulated in epilepsy patients and rat models
PMID: 36811190
6
SLITRK5 dysregulation is associated with Friedreich ataxia
PMID: 39519164
7
No genetic association found between SLITRK5 and Tourette syndrome
PMID: 25426764
Disease Associationsⓘ20
autism spectrum disorderOpen Targets
0.42Moderate
frozen shoulderOpen Targets
0.35Weak
diabetes mellitusOpen Targets
0.34Weak
preeclampsiaOpen Targets
0.34Weak
Abnormal brain morphologyOpen Targets
0.27Weak
alopecia areataOpen Targets
0.26Weak
ovarian dysfunctionOpen Targets
0.22Weak
jaw diseaseOpen Targets
0.22Weak
hypertrophic cardiomyopathyOpen Targets
0.20Weak
respiratory failureOpen Targets
0.20Weak
ovarian neoplasmOpen Targets
0.19Weak
kidney diseaseOpen Targets
0.19Weak
ankylosing spondylitisOpen Targets
0.19Weak
cervical carcinomaOpen Targets
0.18Weak
Abruptio PlacentaeOpen Targets
0.17Weak
connective tissue diseaseOpen Targets
0.17Weak
corneal ulcerOpen Targets
0.17Weak
obsessive-compulsive disorderOpen Targets
0.08Suggestive
Trichodysplasia - xerodermaOpen Targets
0.04Suggestive
trichodysplasia-xeroderma syndromeOpen Targets
0.04Suggestive
Pathogenic Variants1
NM_001384609.1(SLITRK5):c.2515G>C (p.Glu839Gln)Likely pathogenic
Abnormal brain morphology
★☆☆☆→ Residue 839
View on ClinVar ↗
Related Genes
DLGAP3Protein interaction94%SLITRK3Shared pathway75%SLITRK2Shared pathway60%SLITRK4Shared pathway50%SLITRK6Shared pathway50%SLITRK1Shared pathway43%
Tissue Expression6 tissues
Brain
100%
Ovary
10%
Bone Marrow
10%
Heart
10%
Liver
3%
Lung
3%
Gene Interaction Network
Click a node to explore
SLITRK5DLGAP3SLITRK3SLITRK2SLITRK4SLITRK6SLITRK1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O94991
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.61Intermediate
Observed/Expected LoF0.39 [0.28–0.55]
RankingsWhere SLITRK5 stands among ~20K protein-coding genes
  • #10,091of 20,598
    Most Researched41
  • #5,162of 5,498
    Most Pathogenic Variants1
  • #3,566of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedSLITRK5
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.
PMID: 35685361
Comput Struct Biotechnol J · 2022
1.00
2
Association study of the SLITRK5 gene and Tourette syndrome.
PMID: 25426764
Psychiatr Genet · 2015
0.90
3
The Role of SliTrk5 in Central Nervous System.
PMID: 35872846
Biomed Res Int · 2022
0.80
4
SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts.
PMID: 34326333
Nat Commun · 2021
0.70
5
Upregulation of SLITRK5 in patients with epilepsy and in a rat model.
PMID: 36811190
Synapse · 2023
0.60