Histamine N-methyltransferase (HMT, HNMT) is an enzyme that in humans is encoded by the HNMT gene.
Histamine N-methyltransferase is one of two enzymes involved in the metabolism of histamine, the other being diamine oxidase. Histamine N-methyltransferase catalyzes the methylation of histamine in the presence of S-adenosylmethionine (SAM) forming N-methylhistamine. HMT is present in most body tissues but is not present in serum. Histamine N-methyltransferase is encoded by a single gene which has been mapped to chromosome 2.
In mammals, histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative deamination via diamine oxidase. This gene encodes the first enzyme which is found in the cytosol and uses S-adenosyl-L-methionine as the methyl donor. In the mammalian brain, the neurotransmitter activity of histamine is controlled by N(tau)-methylation as diamine oxidase is not found in the central nervous system. A common genetic polymorphism affects the activity levels of this gene product in red blood cells.
Wang L, Thomae B, Eckloff B, Wieben E, Weinshilboum R (August 2002). "Human histamine N-methyltransferase pharmacogenetics: gene resequencing, promoter characterization, and functional studies of a common 5'-flanking region single nucleotide polymorphism (SNP)". Biochem. Pharmacol.64 (4): 699–710. doi:10.1016/s0006-2952(02)01223-6. PMID12167489.
García-Martín E, Martínez C, Benito-León J, Calleja P, Díaz-Sánchez M, Pisa D, Alonso-Navarro H, Ayuso-Peralta L, Torrecilla D, Agúndez JA, Jiménez-Jiménez FJ (February 2010). "Histamine-N-methyl transferase polymorphism and risk for multiple sclerosis". Eur. J. Neurol.17 (2): 335–8. doi:10.1111/j.1468-1331.2009.02720.x. PMID19538200.
Ross CJ, Katzov-Eckert H, Dubé MP, Brooks B, Rassekh SR, Barhdadi A, Feroz-Zada Y, Visscher H, Brown AM, Rieder MJ, Rogers PC, Phillips MS, Carleton BC, Hayden MR (December 2009). "Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy". Nat. Genet.41 (12): 1345–9. doi:10.1038/ng.478. PMID19898482.
Chen GL, Zhu B, Nie WP, Xu ZH, Tan ZR, Zhou G, Liu J, Wang W, Zhou HH (September 2004). "Single nucleotide polymorphisms and haplotypes of histamine N-methyltransferase in patients with gastric ulcer". Inflamm. Res.53 (9): 484–8. doi:10.1007/s00011-004-1290-0. PMID15551002.
Stevenson J, Sonuga-Barke E, McCann D, Grimshaw K, Parker KM, Rose-Zerilli MJ, Holloway JW, Warner JO (September 2010). "The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children's ADHD symptoms". Am J Psychiatry167 (9): 1108–15. doi:10.1176/appi.ajp.2010.09101529. PMID20551163.
Horton JR, Sawada K, Nishibori M, Zhang X, Cheng X (September 2001). "Two polymorphic forms of human histamine methyltransferase: structural, thermal, and kinetic comparisons". Structure9 (9): 837–49. doi:10.1016/S0969-2126(01)00643-8. PMID11566133.