A gain-of-function missense variant in the KCNJ2 gene was identified in monozygotic twins displaying a short QT interval and an autism/epilepsy phenotype and their mother, whose motor clumsiness, obsessive-compulsive symptoms, mood swings with impulsivity, and motor and vocal tics fit a diagnosis of Tourette Syndrome (Ambrosini et al., 2014); these twins had previously been reported to also carry a gain-of-function missense variant in the KCNJ10 gene (Sicca et al., 2011).
Molecular Function
The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Involved in long QT syndrome 7 (LQT7) [MIM:170390], short QT syndrome 3 (SQT3) [MIM:609622], and atrial fibrillation, familial, 9 (ATFB9) [MIM:613980].
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism-epilepsy phenotype.
Transgenic expression of Irk2 in the alpha, beta core and gamma Kenyon cells of mushroom bodies leads to reduced passive avoidance of chamber based on odorant cues.
References
Type
Title
Author, Year
Primary
FoxP influences the speed and accuracy of a perceptual decision in Drosophila.
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Kir2.1/ Irk1 expression driven under FoxP in Kenyon cells whose axons extend to the alpha-beta and gamma cores of the mushroom bodies, expressing this ion channel inactivates the neurons. The expression of the inward correcting potassium ion channel was tuned by temperature sensitive Gal80-ts, these mutants express low levels of the ion channel.
Allele Type: Conditional gain-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Kir2.1/ Irk1 expression driven under FoxP in Kenyon cells whose axons extend to the alpha-beta and gamma cores of the mushroom bodies, expressing this ion channel inactivates the neurons. The expression of the inward correcting potassium ion channel was tuned by temperature sensitive Gal80-ts, these mutants express high levels of the ion channel.
Allele Type: Conditional gain-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Kir2.1/ Irk1 expression driven under FoxP in alpha-beta neurons, expressing this ion channel inactivates the neurons. The expression of the inward correcting potassium ion channel was driven by NP6024-Gal4 driver.
Allele Type: Conditional gain-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Transgenic
Mutation:
Kir2.1/ Irk1 expression driven under FoxP in gamma Kenyon cells, expressing this ion channel inactivates the neurons. The expression of the inward correcting potassium ion channel was driven by NP1131-Gal4 driver.
Allele Type: Conditional gain-of-function
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Cued or contextual fear conditioning: passive avoidance: odor discrimination1
Decreased
Description: Irk1 mutants showed increased reaction time at high concentration difference(between reinforced and other odor) compared to controls.
Exp Paradigm: High concentration ratios
Cued or contextual fear conditioning: passive avoidance: odor discrimination1
Decreased
Description: Irk1 mutants showed a decrease in odor discrimination accuracy (i.e., fraction correct) at either intermediate or high concentration ratios compared to controls.
Exp Paradigm: Intermediate and high concentration ratios
Cued or contextual fear conditioning: passive avoidance: odor discrimination1
Decreased
Description: Irk1 mutants show a decrease in odor discrimination accuracy (i.e., fraction correct) and an increase in reaction time at high concentration difference (between reinforced and other odor) compared to controls.
Exp Paradigm: High concentration ratios
