Functionally-impairing missense variants in the SLC12A5 previously observed in epilepsy cases were identified in probands from a Quebec ASD cohort. Subsequent analysis of a combined dataset indicated that there was an enrichment of coding variants in the target region of the C-terminus of KCC2 in ASD cases compared to controls (P=0.03); this statistically significant enrichment increased when considering variants in this region that either disrupted or introduced a CpG site (P=6.8E-03) (Merner et al., 2015).
Molecular Function
This gene encodes an integral membrane K-Cl cotransporter that mediates electroneutral potassium-chloride cotransport in mature neurons and is important for Cl-homeostasis in neurons. Mutations in this gene have been associated with febrile seizures (Puskarjov et al., 2014), idiopathic generalized epilepsy (Kahle et al., 2014), and epilepsy of infancy with migrating focal seizures (Stodberg et al., 2015).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia.
Disruption of KCC2 in Parvalbumin-Positive Interneurons Is Associated With a Decreased Seizure Threshold and a Progressive Loss of Parvalbumin-Positive Interneurons
