The protein encoded by this gene is a non-selective calcium-permeablecation channel and is part of theTransient Receptor Potential ion channel super family. The closest relative is the cold andmenthol activatedTRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat.[5] The TRPM2 ion channel is activated by free intracellularADP-ribose in synergy with free intracellularcalcium.[6] ADP-Ribose is produced to by the enzymePARP in response tooxidative stress and confers susceptibility tocell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.[7]
TheTRPM2 gene is highly expressed in the brain and was implicated by both genetic linkage studies in families[8] and then by case control or trio allelic association studies in the genetic aetiology ofbipolar affective disorder (Manic Depression).[9][10]
The physiological role of TRPM2 is not well understood. It was shown to be involved ininsulin secretion.[5][11] In theimmune cells it mediates parts of the responses toTNF-alpha.[12] A role has been suggested for TRPM2 in activation ofNLRP3inflammasome, the dysregulation of which is strongly associated with a number of auto inflammatory and metabolic diseases, such as gout, obesity and diabetes.[13] In the brain it is involved in the toxicity ofamyloid beta, a protein associated withAlzheimer's disease.[14] In 2016, TRPM2 channel was shown to be strongly implicated in the detection of non-painful warm stimuli. Chun-Hsiang Tan and Peter McNaughton studied the responses of actualsensory neurons to thermal stimuli, then used an RNA-sequencing strategy to identify TRPM2 as genetically required for warmth detection in the non-noxious range of 33–38 °C.[15]
^McQuillin A, Bass NJ, Kalsi G, Lawrence J, Puri V, Choudhury K, Detera-Wadleigh SD, Curtis D, Gurling HM (2006). "Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3".Molecular Psychiatry.11 (2):134–42.doi:10.1038/sj.mp.4001759.PMID16205735.S2CID22030624.
^Xu C, Macciardi F, Li PP, Yoon IS, Cooke RG, Hughes B, Parikh SV, McIntyre RS, Kennedy JL, Warsh JJ (2006). "Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder".American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics.141B (1):36–43.doi:10.1002/ajmg.b.30239.PMID16252251.S2CID6439507.
Clapham DE, Julius D, Montell C, Schultz G (2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels".Pharmacological Reviews.57 (4):427–50.doi:10.1124/pr.57.4.6.PMID16382100.S2CID17936350.
