RBFOX1, A Splicing Regulator, is A Candidate Gene For Aggressive Behavior

Abstract The RBFOX1 gene (or A2BP1) encodes a splicing factor important for neuronal development that has been related to autism spectrum disorder and other neurodevelopmental phenotypes. Evidence suggests that this gene contributes to aggressive behavior. Suggestive associations with RBFOX1 have been identified in genome-wide association studies (GWAS) of anger, conduct disorder and aggressive behavior. Also, variants in this gene have been shown to contribute to temporal lobe volume, a brain area that is altered in several aggression phenotypes. In animals, this gene has been shown to modulate aggressive behavior in Drosophila. RBFOX1 has also been associated with canine aggression and is upregulated in mice that show increased aggression after frustration of an expected reward. Several associations as well as duplications and deletions affecting RBFOX1 have been identified in several psychiatric and neurodevelopmental disorders, often presenting aggressive behaviors. In this review, we summarize this evidence and provide new results for implicating RBFOX1 in aggressiveness. However, further studies are required to provide more detail on the contribution of this gene to this complex phenotype.