Mutations Position Table
MAPT R406 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| R406Q |
Frontotemporal Dementia Spectrum : Uncertain Significance | Substitution | Substitution | Missense | Coding | Exon 13 | Unknown, but MRI of one carrier showed mild bilateral frontal and temporal lobe atrophy, and in another, flortaucipir-PET showed tau pathology in bilateral medial temporal lobe regions. |
Reduced microtubule binding and assembly and increased tau aggregation in vitro. In cells, increased phosphorylation at T205, T231, and S396, and decreased it at S404. |
Cheng et al., 2023 |
| R406W |
Frontotemporal Dementia Spectrum : Likely Pathogenic | Substitution | Substitution | Missense | Coding | Exon 13 | Bilateral frontotemporal atrophy. Neuronal loss, ballooned neurons, gliosis, and abundant tau-positive inclusions, including neurofibrillary tangles. Early stage atrophy in the hippocampus, amygdala, medial and lateral temporal cortex, and temporal pole, as well as anterior and posterior insular cortex. Generally sparse or absent Aβ plaques. |
Generates tau filaments with the AD fold, disrupts microtubule dynamics (although results are mixed). Alters neuronal and glial function, including effects on axons, dendrites, calcium dynamics, neurotransmitter receptors, lysosomes, autophagy, tau-membrane interactions, actin dynamics, nucleus and chromatin structure, transcriptional regulation, and lipid physiology. |
Hutton et al., 1998 |
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