Whole-exome sequencing of five families in which second- and third-degree relatives were affected with autism identified a novel private missense variant (p.Cys1143Phe) in the second intracellular loop of the Nav1.7 sodium channel (encoded by the SCN9A gene) that exhibited partial loss-of-function effects. An excess of rare missense variants in the same intracellular loop was subsequently observed in a case-control variant-burden study of 1004 familial ASD cases and 1127 controls (29 in cases vs. 2 in controls; P=5.1E-07), with one of the variants (p.Met932Leu/Val991Leu) also showing functional effects (Rubinstein et al., 2016).
Molecular Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na+ions may pass in accordance with their electrochemical gradient. Plays a role in pain mechanisms, especially in the development of inflammatory pain.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Association of rare missense variants in the second intracellular loop of NaV1.7 sodium channels with familial autism.
