Dopamine Receptor D4 (DRD4) has been suggested to affect personality, substance dependence, cognition, and emotion. DRD4 binds the antipsychotic medications clozapine and spiperone. The DRD4 gene contains extensive polymorphisms consisting of variable numbers of tandem repeats (VNTR) in sequences corresponding to the third cytoplasmic loop of the receptor; at least 27 different haplotypes encoding 20 different protein variants have been documented. The frequency of the different variants varies among population groups. Studies have suggested a link between VNTR and human personality traits (such as novelty seeking) and diseases (such as schizophrenia, bipolar affective disorder, and Tourette syndrome); however, considerable debates exist regarding the validity and significance of such associations. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804