Mutations Position Table
PSEN2 N141 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| N141I |
AD : Pathogenic | Substitution | Splicing Alteration; Substitution | Deletion; Missense | Coding | Exon 6 | Extensive amyloid plaques; Extensive neurofibrillary tangles (typically a Braak score of V or VI); α-synuclein inclusions, especially in the amygdala; Rare TDP-43 pathology; Hippocampal sclerosis. |
Endolysosomal deficits that accelerate AD pathogenesis. Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in PSEN2-CTF and PSEN2-NTF. Altered microglial phenotype. In 3-D brain organoids, elevated Aβ42/Aβ40 ratio, asynchronous calcium transients, and neuronal hyperactivity. Cytokine overproduction in mice. Exon 6 skipping in ~10% of mutated transcripts, reduced mRNA stability. |
Levy-Lahad et al., 1995; Rogaev et al., 1995; Morales et al., 2024 |
| N141S |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 6 | Unknown. |
Unknown, but in silico algorithms predicted damaging (CADD > 20). |
Mao et al., 2021 |
| N141D |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 6 | Unknown |
Unknown, but 3 algorithms predict damaging with a PHRED CADD score of 24.9. |
Wang et al., 2019 |
| N141Y |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 6 | Proband had autopsy-confirmed AD with severe brain atrophy and numerous plaques and neurofibrillary tangles. |
Increased Aβ42/Aβ40 ratio and decreased Aβ37/Aβ42 ratio in cultured cells. |
Niu et al., 2014 |
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