Mutations

PSEN1 L173S

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73653598 T>C
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: TTG to TCG
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 6

Findings

This mutation was found in a Han Chinese individual diagnosed with possible AD according to the NINCDS-ADRDA and DSM-IV criteria (Wang et al., 2019). The patient had at least one affected first- or second-degree relative and age at onset was 38 years. 

Neuropathology

Unknown

Biological Effect

The mutation was predicted to be damaging by four different algorithms, with a PHRED-CADD score of 24.1. A cryo-electron microscopy study of the atomic structure of γ-secretase bound to an APP fragment indicates the L173 residue is apposed to the APP transmembrane helix, with its side-chain reaching towards the interior of the substrate-binding pore (Zhou et al., 2019; Jan 2019 news).

Last Updated: 13 Aug 2019

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References

News Citations

  1. CryoEM γ-Secretase Structures Nail APP, Notch Binding

Paper Citations

  1. Wang G, Zhang DF, Jiang HY, Fan Y, Ma L, Shen Z, Bi R, Xu M, Tan L, Shan B, Yao YG, Feng T. Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease. J Psychiatr Res. 2019 Jun;113:141-147. Epub 2019 Mar 30 PubMed.
  2. Zhou R, Yang G, Guo X, Zhou Q, Lei J, Shi Y. Recognition of the amyloid precursor protein by human γ-secretase. Science. 2019 Feb 15;363(6428) Epub 2019 Jan 10 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. Wang G, Zhang DF, Jiang HY, Fan Y, Ma L, Shen Z, Bi R, Xu M, Tan L, Shan B, Yao YG, Feng T. Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease. J Psychiatr Res. 2019 Jun;113:141-147. Epub 2019 Mar 30 PubMed.

Other mutations at this position

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