Relevance to Autism

Bosman et al., 2024 reported de novo missense variants in the TRPM7 gene in three unrelated individuals presenting with hypomagnesemia, autism spectrum disorder, and developmental delay; all three missense variants were shown experimentally to result in loss-of-function of TRPM7-mediated magnesium uptake in transfected HEK293 cells with no effects on expression or plasma membrane insertion. Rare genetic variation in TRPM7 had previously been associated with hypomagnesemia with or without seizures (Lei et al., 2022; Vargas-Poussou et al., 2023). Rare de novo missense variants in TRPM7 have also been identified in three ASD probands from the Simons Simplex Collection, the Autism Sequencing Consortium, and the SPARK cohort (Iossifov et al., 2014; Satterstrom et al., 2020; Zhou et al., 2022), while de novo loss-of-function variants in this gene have been reported in two ASD probands (Zhou et al., 2022; Fu et al., 2022).

Molecular Function

This gene belongs to the melastatin subfamily of transient receptor potential family of ion channels. The protein encoded by this gene is both an ion channel and a serine/threonine protein kinase. The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. The encoded protein is involved in cytoskeletal organization, cell adhesion, cell migration and organogenesis. A heterozygous missense variant in this gene that was shown experimentally to increase susceptibility to inhibition by intracellular magnesium concentrations compared to wildtype channels (p.Thr1482Ile) is a cause of amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam (Hermosura et al., 2005). The gene may also be associated with defects of cardiac function.

External Links

References