HNMT Gene: Histamine N-Methyltransferase – Function, Mutations, and Disease Associations

The HNMT gene encodes histamine N-methyltransferase, a cytosolic enzyme that catalyzes the methylation of histamine to N-methylhistamine, a key step in histamine degradation. HNMT is expressed in various tissues including kidney, liver, lung, and brain, and plays a critical role in modulating histamine-mediated inflammatory and neurological responses. Genetic variants in HNMT have been associated with altered enzyme activity and susceptibility to asthma, allergy, and certain neurological disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Histamine degradation (Reactome: R-HSA-2142691)

• Histidine metabolism (KEGG: hsa00340)

• Monoamine metabolism (WikiPathways: WP550)

Histamine N-methyltransferase (HNMT) is a 292-amino-acid cytosolic enzyme that methylates histamine using S-adenosyl-L-methionine as a methyl donor. The protein is a monomer with a molecular weight of approximately 33 kDa. HNMT is the primary enzyme responsible for histamine inactivation in mammalian tissues, particularly in the kidney and liver. Structural studies reveal a conserved methyltransferase fold with a deep active site pocket that accommodates histamine. Polymorphisms such as Thr105Ile reduce enzyme stability and activity, leading to elevated histamine levels and increased risk for allergic and inflammatory conditions.