Relevance to Autism

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