Mutations Position Table
MAPT N296 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| N296N |
Frontotemporal Dementia Spectrum : Likely Pathogenic | Substitution | Splicing Alteration | Isoform Shift; Silent | Coding | Exon 10 | Frontotemporal atrophy; Neuronal loss in the globus pallidus, substantia nigra, and locus ceruleus; Swollen achromatic neurons and tau-positive inclusions throughout the brain; Plaques and tangles were rare in the hippocampus and cerebral cortex. |
Increased inclusion of exon 10 in tau mRNA and thus increased the ratio of 4R/3R tau protein. |
Spillantini et al., 2000 |
| N296del (delN296, ΔN296) |
Frontotemporal Dementia Spectrum : Likely Pathogenic, PD : Not Classified | Deletion | Splicing Alteration | Deletion; Isoform Shift | Coding | Exon 10 | Atrophy of the right precentral gyrus and the brainstem, as well as neuron loss and gliosis in the substantia nigra, several brainstem nuclei, and diencephalon. Hyperphosphorylated tau and neurofibrillary tangles in neurons in many brain regions. Accumulated tau in astrocytes and oligodendrocytes. |
Mixed results. Effects reported on microtubule dynamics, tau aggregation, and splicing, but none were consistent across studies. |
Pastor et al., 2001 |
| N296D |
Frontotemporal Dementia Spectrum : Not Classified | Substitution | Splicing Alteration | Isoform Shift; Missense | Coding | Exon 10 | Unknown; imaging showed temporal atrophy. |
In a cell-based assay, increased inclusion of exon 10. |
Cohn-Hokke et al., 2014 |
| N296H |
Frontotemporal Dementia Spectrum : Not Classified | Substitution | Splicing Alteration | Isoform Shift; Missense | Coding | Exon 10 | Localized frontotemporal lobe atrophy; accumulation of four-repeat (4R) tau; phosphorylated tau-positive neurons, astrocytes, and oligodendrocytes. Inclusions consistent with globular glial tauopathy. |
Increased inclusion of exon 10 in tau mRNA; increased ratio of 4R/3R tau. Reduced tau's ability to promote tubulin polymerization and microtubule assembly. Little to no effect on tau filament formation. In mice, alterations of tau phosphorylation and behavioral abnormalities (hyperactivity, anxiety, depressive-like state). |
Iseki et al., 2001 |
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