Mutations Position Table

PSEN1 A246 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
A246E
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Generalized atrophy, most prominently in the frontal lobes and hippocampus. Neuronal loss, gliosis, neurofibrillary tangles, and plaques.

Increased Aβ42 and Aβ43 secretion, Aβ42/Aβ40 ratio, Aβ42/Aβ total ratio. Decreased production of Aβ40 and Aβ42 in vitro. Disrupts endosomes via accumulation of APP β-CTF. Impaired neuronal differentiation, neural precursor proliferation, viability, autophagy, mitophagy, lysosomal function, ER calcium flux. 

rs63750526
Coding
Exon 7
Point, Missense
GCG to GAG
4 Sherrington et al., 1995
A246P
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Neuropathology consistent with AD (Braak and Braak stage VI, CERAD C) as well as cerebral amyloid angiopathy. Some α-synuclein inclusions were observed in the entorhinal cortex.

Unknown; predicted probably damaging in silico.


Coding
Exon 7
Point, Missense
GCG to CCG
0 Roeber et al., 2015

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