Mutations Position Table

PSEN2 N141 Mutations

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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.

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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