Human indolethylamine N-methyl-transferase (INMT) pharmacogenetics: CDNA and gene cloning and chromosomal localization

Methylation is an important pathway in the metabolism of many drugs and endogenous molecules. INMT catalyzes the N-methylation of tryptamine and 5-HT in rabbit tissue. We initially cloned the rabbit INMT cDNA and gene and then used a PCR-based strategy to clone the human INMT cDNA. The ORF of this cDNA was 792 bp in length, with a 16 bp 5′-UTR and a 1754 bp 3′-UTR. The predicted amino acid sequence was 88% identical to that of rabbit INMT. Northern blots indicated that the transcript was expressed in many tissues. The human INMT gene was then cloned by screening a BAC genomic DNA library with the human INMT cDNA. The human INMT gene structure was similar to that of the rabbit INMT gene and contained 3 exons. The introns were 1426 bp and 1479 bp in length. The 5′ flanking region did not contain a TATA box. The human gene mapped to chromosome 7. cDNA and gene cloning and the chromosomal localization of the human INMT gene represent steps toward studying the pharmacogenetics of this methyltransferase enzyme in humans.