Mutations

APOE c.43+64C>T (rs143063029)

Other Names: rs143063029

Overview

Position: (GRCh38/hg38):Chr19:44906731 C>T
Position: (GRCh37/hg19):Chr19:45409988 C>T
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs143063029
Coding/Non-Coding: Non-Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Reference Isoform: APOE Isoform 1
Genomic Region: Intron 2

Findings

This intronic variant was described in an exome-wide analysis of 157,160 individuals of the UK Biobank aimed at identifying genetic variants associated with cognition during aging (Chakraborty and Kahali, 2023). An interaction between c.43+64C>T and a variant of the low-density lipoprotein receptor-related protein1 (LRP1) gene, rs138993371, was found to be associated with visual attention (effect size=0.20, CHISQ test statistic=5.45, p-value=0.019). The interaction was one of nine significant interactions between five APOE variants and eight LRP variants associated with visual attention. Of note, the protein encoded by LRP1 is an endocytic receptor implicated in AD pathology whose ligands include ApoE and Aβ (Shinohara et al., 2017).

This variant was reported in the gnomAD variant database at a global frequency of 0.0007, including 22 heterozygous carriers, most of non-Finnish European ancestry (gnomAD v2.1.1, June 2023).

Biological Effect

The biological effect of this variant is unknown. Its PHRED-scaled CADD score (4.94), which integrates diverse information in silico, was well below 20, a commonly used threshold to predict deleteriousness (CADD v.1.6, June 2023).

Last Updated: 12 Jun 2023

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References

Paper Citations

  1. Chakraborty S, Kahali B. Exome-wide analysis reveals role of LRP1 and additional novel loci in cognition. HGG Adv. 2023 Jul 13;4(3):100208. Epub 2023 May 20 PubMed.
  2. Shinohara M, Tachibana M, Kanekiyo T, Bu G. Role of LRP1 in the pathogenesis of Alzheimer's disease: evidence from clinical and preclinical studies. J Lipid Res. 2017 Jul;58(7):1267-1281. Epub 2017 Apr 4 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. Chakraborty S, Kahali B. Exome-wide analysis reveals role of LRP1 and additional novel loci in cognition. HGG Adv. 2023 Jul 13;4(3):100208. Epub 2023 May 20 PubMed.

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