Gene Name: SLIT and NTRK like family member 5 Aliases: LRRC11, bA364G4.2 Chromosome No: 13 Chromosome Band: 13q31.2 Genetic Category: Functional-Rare single gene variant-
A maternally-inherited nonsense variant in the SLITRK5 gene was identified in a male ASD proband, but not in this proband's ASD-affected brother, in Tammimies et al., 2015. Rare de novo missense variants that were predicted to be possibly damaging, as well as a de novo synonymous variant predicted to change an exonic splicing regulator, affect a DNase I hypersensitive site, and result in the gain of a miRNA target, were identified in the SLITRK5 gene in ASD probands from the Simons Simplex Collection (Iossifov et al., 2012; Iossifov et al., 2014; Takata et al., 2016). SLITRK5 variants that resulted in impaired synapse formation were identified in OCD probands in Song et al., 2017. Loss of Slitrk5 had previously been shown to result in OCD-like behaviors in mice, which manifests as excessive self-grooming and increased anxiety-like behaviors (Shmelkov et al., 2010).
Molecular Function
This gene enocdes a protein that suppresses neurite outgrowth; it is expressed predominantly in the cerebral cortex of the brain but also at low levels in the spinal cord and medulla.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Targeted replacement of entire encoding exon of Slitrk5 gene with lacZ gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Targeted replacement of entire encoding exon of Slitrk5 gene with lacZ gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Description: Decreased dendritic complexity indicated by decrease in dendritic arbor complexity and greater distance from soma
Exp Paradigm: Sholl analysis and fractal dimension analysis
Description: Abnormal brain morphology indicated by decreased volume ratio of striatum with no change in volume ratios of dorsal hippocampus
Exp Paradigm: Anatomical analyses of cortex and striatum
Description: Increased anxiety indicated by less time spent in center compartment; lower number of entries into center compartment ; reduced time spent in open arms
Exp Paradigm: Elevated plus maze test
Description: Increased anxiety indicated by less time spent in center compartment; lower number of entries into center compartment ; reduced time spent in open arms
Exp Paradigm: Open field test
Description: Abnormal fosb expression demonstrated by upregulation in orbitofrontal cortex and no change in caudate putamen, hippocampus and thalamus
Exp Paradigm: Fosb expression
