RASL11A encodes RAS Like Family 11 Member A, a member of the small GTPase protein family with a high degree of similarity to RAS proteins (Fig. 1 and Table 3). The GTPase H-ras encoded by HRAS in the nucleus accumbens plays a key role in neuroadaptations that underlie excessive alcohol-drinking behaviors in mice (Ben Hamida et al., 2012), while the GTPase K-ras encoded by KRAS is differentially expressed after repeated alcohol in the anterior cingulate cortex and alcohol differentially affected various pathways in a K-ras dependent manner suggesting that K-ras-regulatory pathways play a key role in excessive alcohol drinking after a history of dependence (Repunte-Canonigo et al., 2010). Thus genetic variation affecting the regulation of RASL11A could likely play a role in behaviors associated with protracted abstinence from alcohol and thus represents a novel and compelling candidate gene based on human GWAS and molecular biology studies in rodents.
