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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SLITRK2
SLIT and NTRK like family member 2
Chromosome X Β· Xq27.3
NCBI Gene: 84631Ensembl: ENSG00000185985HGNC: HGNC:13449UniProt: B3KTY4
23PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
plasma membranedendriteregulation of synapse organizationaxonogenesisintellectual developmental disorder, X-linked 111Intellectual disabilitygoutdyslexia
✦AI Summary

SLITRK2 is a postsynaptic transmembrane adhesion protein that functions primarily in excitatory synapse development and maintenance 1. The protein promotes excitatory synaptogenesis through interaction with presynaptic receptors, particularly receptor protein tyrosine phosphatases, via splicing-dependent trans-synaptic adhesion mechanisms 2. SLITRK2 negatively regulates TrkB (NTRK2) receptor levels in neurons 1. On dopaminergic neurons, SLITRK2 specifically promotes excitatory synaptic inputs while its family member Slitrk5 promotes inhibitory synapses; this balance is critical for normal locomotor activity 3. Functionally, SLITRK2 suppresses neurite outgrowth and regulates synapse organization 4. Clinically, SLITRK2 variants cause X-linked neurodevelopmental disorders characterized by intellectual disability, impaired spatial memory, and abnormal gait 1. Additionally, SLITRK2 variants modulate age-at-onset in C9orf72-associated frontotemporal dementia; higher SLITRK2 expression correlates with earlier disease onset and reduced synaptic vesicle proteins 5. Beyond neurodevelopment, elevated SLITRK2 expression associates with poor prognosis and advanced disease stage in gastric cancer, potentially through effects on immune cell infiltration 6.

Sources cited
1
SLITRK2 is a postsynaptic transmembrane protein that regulates neurite outgrowth and excitatory synapse maintenance, negatively regulates TrkB levels, and variants cause X-linked neurodevelopmental disorders with impaired memory and gait
PMID: 35840571
2
Structure of Slitrk2-PTPΞ΄ complex reveals splicing-dependent trans-synaptic adhesion mechanisms for synaptogenic differentiation
PMID: 25989451
3
Slitrk2 promotes excitatory synaptic inputs on dopamine neurons; balance with Slitrk5-mediated inhibitory synapses is critical for normal locomotor activity
PMID: 32075770
4
Slitrk1 and Slitrk2 regulate synapse formation; overexpression increases synaptic contacts and decreased expression reduces excitatory synapses
PMID: 27273464
5
SLITRK2 variants modify age-at-onset in C9orf72 frontotemporal dementia; higher expression correlates with earlier onset and reduced synaptic vesicle proteins
PMID: 34687211
6
Elevated SLITRK2 expression associates with advanced tumor stage, poor overall survival, and reduced disease-free survival in gastric cancer through immune cell infiltration
PMID: 39550447
Disease Associationsβ“˜21
intellectual developmental disorder, X-linked 111Open Targets
0.51Moderate
Intellectual disabilityOpen Targets
0.39Weak
goutOpen Targets
0.21Weak
dyslexiaOpen Targets
0.21Weak
familial renal glucosuriaOpen Targets
0.12Weak
cancerOpen Targets
0.07Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
Testicular regression syndromeOpen Targets
0.05Suggestive
46,XX gonadal dysgenesisOpen Targets
0.05Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.05Suggestive
primary ovarian insufficiencyOpen Targets
0.05Suggestive
cervical adenocarcinomaOpen Targets
0.04Suggestive
cervical cancerOpen Targets
0.04Suggestive
cervical carcinomaOpen Targets
0.04Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.04Suggestive
gastric cancerOpen Targets
0.04Suggestive
hepatocellular adenomaOpen Targets
0.04Suggestive
spinocerebellar ataxia type 14Open Targets
0.04Suggestive
gonadoblastomaOpen Targets
0.04Suggestive
Intellectual developmental disorder, X-linked 111UniProt
Pathogenic Variants5
NM_032539.5(SLITRK2):c.934A>G (p.Thr312Ala)Likely pathogenic
Intellectual disability|Intellectual developmental disorder, X-linked 111
β˜…β˜†β˜†β˜†2025β†’ Residue 312
NM_032539.5(SLITRK2):c.1381G>T (p.Glu461Ter)Pathogenic
Intellectual developmental disorder, X-linked 111|Intellectual disability
β˜†β˜†β˜†β˜†2023β†’ Residue 461
NM_032539.5(SLITRK2):c.1121C>G (p.Pro374Arg)Pathogenic
Intellectual disability|Intellectual developmental disorder, X-linked 111
β˜†β˜†β˜†β˜†2023β†’ Residue 374
NM_032539.5(SLITRK2):c.1276C>T (p.Arg426Cys)Pathogenic
Intellectual disability|Intellectual developmental disorder, X-linked 111
β˜†β˜†β˜†β˜†2023β†’ Residue 426
NM_032539.5(SLITRK2):c.221T>C (p.Leu74Ser)Likely pathogenic
Intellectual disability
β˜†β˜†β˜†β˜†2022β†’ Residue 74
View on ClinVar β†—
Related Genes
NPTX1Protein interaction81%PTPRSProtein interaction81%SLITRK3Shared pathway80%SLITRK1Shared pathway71%PTPRDProtein interaction66%SLITRK4Shared pathway60%
Tissue Expression6 tissues
Brain
100%
Heart
23%
Lung
10%
Ovary
5%
Liver
3%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
SLITRK2NPTX1PTPRSSLITRK3SLITRK1PTPRDSLITRK4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9H156
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.58Moderately Constrained
pLIβ“˜
0.75Intermediate
Observed/Expected LoF0.37 [0.24–0.58]
RankingsWhere SLITRK2 stands among ~20K protein-coding genes
  • #13,525of 20,598
    Most Researched23
  • #3,629of 5,498
    Most Pathogenic Variants5
  • #3,918of 17,882
    Most Constrained (LOEUF)0.58 Β· top quartile
Genes detectedSLITRK2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice.
PMID: 35840571
Nat Commun Β· 2022
1.00
2
SLITRK2 as a prognostic and immunological biomarker in gastric cancer.
PMID: 39550447
Discov Oncol Β· 2024
0.90
3
Opposite Control of Excitatory and Inhibitory Synapse Formation by Slitrk2 and Slitrk5 on Dopamine Neurons Modulates Hyperactivity Behavior.
PMID: 32075770
Cell Rep Β· 2020
0.80
4
SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration.
PMID: 34687211
Brain Β· 2021
0.70
5
Slitrk1 is localized to excitatory synapses and promotes their development.
PMID: 27273464
Sci Rep Β· 2016
0.60