TRPM6

TRPM6 is the acronym for "Transient receptor potential cation channel, subfamily M, member 6". The melastatin-related transient receptor potential (TRP) channel is a selective cation channel whose loss of function is associated with hypomagnesemia with secondary hypocalcemia (E83.4). The gene of the same name is located on chromosome 9q21.13 and encodes several mRNA isoforms (Chubanov et al. 2004).

A Ser141-to-Leu mutation in the TRPM6 gene (OMIN: 607009.0011) leads to the rare clinical picture of "hypomagnesemia with secondary hypocalcemia" (E83.4). Schlingmann et al (2002) studied 5 families (2 Turkish, 1 Swedish, 1 Israeli and 1 Albanian) with this inborn error of metabolism and discovered 7 mutations in the TRPM6 gene (OMIM: 607009.0001-607009.0005). The age at onset of symptoms (tetany, muscle spasms, and seizures due to hypomagnesemia hypocalcemia) varied from 3 weeks to 4 months.

Numerous other cases of TRPM6 mutations have been described (see Walder et al. 2002), demonstrating the essential role of TRPM6 in magnesium homeostasis (Chubanov V et al. 2004). The TRPM6/7 complex mediates Mg2+ influx in human epithelial colon cells and are essential for this purpose (Luongo F et al. 2018).

1. Chubanov V et al (2004) Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. Proc Nat Acad Sci 101: 2894-2899
2. Farooqi A et al. (2011) TRPM channels: same ballpark, different players, and different rules in immunogenetics. Immunogenetics 63: 773-787
3. Luongo F et al. (2018) TRPM6 is essential for Magnesium Uptake and Epithelial Cell Function in the Colon. Nutrients 18:784.
4. Mathar I et al (2014) Handb Exp Pharmacol 222:461-487.
5. Nilius B et al (2011) The transient receptor potential family of ion channels. Genome Biol 12:218.
6. Schlingmann KP et al (2002) Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nature Genet 31: 166-170
7. van der Wijst J et al (2014) Mg2+ homeostasis: the balancing act of TRPM6. Curr Opin Nephrol Hypertens 23:361-369.
8. Walder RY et al (2002) Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nature Genet 31: 171-174