Rare mutations in the KCNJ10 gene have been identified with autism (Sicca et al., 2011). In particular, that study found two non-synonymous SNPs (P18Q and V84M) in unrelated individuals with a seizure disorder who also have ASD and ID. Both of these mutations were shown to be functional in heterologous systems. In addition, genetic association has been found between KCNJ10 and seizure susceptibility in patients with epilepsy (Buono et al., 2004).
Molecular Function
This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K channel Kir4.1.
Transient knockdown of kcnj10a through morpholino -based technology leads to dilation of the pronephric duct, reduction of the size of the swim bladder and increases in spontaneous tail flicks in 30 hpf morphants, commonly linked to neuronal hyperexcitability. Loss-of-function of Kir4.1 channels in zebrafish recapitulate the human behavioral phenotypes including epilepsy. Co-injection of embryos with kcnj10a MO and equimolar amounts of either wildtype or individual mutated human KCNJ10 mRNA (R271C, R18Q, V84M, R348H, R18Q) led to variant specific outcomes. WT and the R271C mRNA rescued the number of spontaneous tail flicks to basal levels. However the R18Q, V84M, R348H mutant human KCNJ10 mRNA could not complement the disease phenotype. WT embryos over-expressing R18Q alone or with WT human mRNA showed abnormal locomotion.
References
Type
Title
Author, Year
Primary
Gain-of-function defects of astrocytic Kir4.1 channels in children with autism spectrum disorders and epilepsy.
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Morpholino targeting the splice junction of kcnj101 were injected into one- to two-cell stage embryos to knock down kcnj10 expression in zebrafish.
Allele Type: Targeted
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Wildtype zebrafish embryos were injected with R18Q over-expresssing cRNA.
Allele Type: Targeted
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
