Mutations

PSEN1 H131R

Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73640327 A>G
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CAC to CGC
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 5

Findings

This mutation was detected in a Japanese woman with apparently sporadic early onset Alzheimer's disease. Cognitive impairment began at age 45 and she met NINCDS-ADRDA criteria for AD (Ikeda et al., 2013).

Neuropathology

Unknown.

Biological Effect

An in vitro assay using purified proteins to test the ability of this mutant to cleave the APP-C99 substrate revealed decreased production of Aβ40 and Aβ42, and a slight increase in the Aβ42/Aβ40 ratio (Sun et al., 2017).

Last Updated: 18 Sep 2019

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References

Paper Citations

  1. . Cerebrospinal fluid levels of phosphorylated tau and Aβ1-38/Aβ1-40/Aβ1-42 in Alzheimer's disease with PS1 mutations. Amyloid. 2013 Jun;20(2):107-12. PubMed.
  2. . Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485. Epub 2016 Dec 5 PubMed.

Further Reading

Learn More

  1. Japanese Familial Alzheimer's Disease Database

Protein Diagram

Primary Papers

  1. . Cerebrospinal fluid levels of phosphorylated tau and Aβ1-38/Aβ1-40/Aβ1-42 in Alzheimer's disease with PS1 mutations. Amyloid. 2013 Jun;20(2):107-12. PubMed.

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