A functional single-nucleotide polymorphism (a common normal variant) of the gene for catechol-"O"-methyltransferase results in a valine to methionine mutation at position 158 (Val158Met) rs4680. In vitro, the homozygous Val variant metabolizes dopamine at up to four times the rate of its methionine counterpart. However, in vivo the Met variant is overexpressed in the brain, resulting in a 40% decrease (rather than 75% decrease) in functional enzyme activity. The lower rates of catabolism for the Met allele results in higher synaptic dopamine levels following neurotransmitter release, ultimately increasing dopaminergic stimulation of the postsynaptic neuron. Given the preferential role of COMT in prefrontal dopamine degradation, the Val158Met polymorphism is thought to exert its effects on cognition by modulating dopamine signaling in the frontal lobes.