Mutations
PSEN1 L173S
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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
References
News Citations
Paper Citations
- 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.
- 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
- 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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