STX is an enzyme responsible for the transfer of polysialic acids (PSA) to a neural cell adhesion molecule (NCAM). Three SNP sites (core SNPs) in the STX promoter region are known to alter the promoter activity and associated with various mental disorders, such as schizophrenia, bipolar disorder and autism, suggesting that STX plays an important role in the human specific brain activity. Based on the combination of core SNPs, the haplotypes of human STX promoter region can be classified into four major promoter types, i.e., “CGC”, “TGT”, “TCT” and “CGT”. Interestingly, the result of promoter assays indicated that the “CGC” type, which has high frequency (35%) in Asian populations, has significantly lower promoter activity than other types. A phylogenetic study using haplotype sequences determined by molecular cloning of 63 individuals from a wide range of ethnic groups revealed that all the promoter types emerged about 0.6 MYA and each type diversified 0.1~0.2 MYA, which is coincidentally prior to the African exodus. Further analysis using haplotype sequences from the 1000 genome project data (2504 individuals) reveals that “CGC” shows high homozygosity in the ~18 kb region surrounding the core SNPs. This is consistent with the small nucleotide diversity in the Asian “CGC” type, result of LRH test and site frequency spectrum analyses. Based on these results, we propose that positive selection has acted on “CGC” in the Asian populations throughout the Great Journey, and is still ongoing.