Phenotype: Blood Lipids/Lipoproteins, Cardiovascular Disease
Reference Assembly: GRCh37/hg19
Position: Chr19:45412337 G>A
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs140808909
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GAG to AAG
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4
This variant is one of two contiguous substitutions of glutamates by lysines in the E262_E263delinsKK (Suita) variant. The Suita variant is associated with increased plasma lipid levels and cardiovascular disease (for additional information on the double substitution go to the Suita detail page).
In the gnomAD variant database, E262K was found only in East Asians at a frequency of 0.003 (gnomAD v2.1.1, Sep 2022).
Of note, a study analyzing whole-genome and whole-exome sequencing data from 138,632 individuals, identified E262K as one of six APOE variants likely to have functional consequences and clinical relevance given their high prevalence in at least one population and their classification by five algorithms (SIFT, Polyphen2, MutationAssessor, PROVEAN, and DANN) as deleterious with high confidence (Zhou et al., 2018). Consistent with this finding, additional in silico algorithms classified the substitution as damaging (Nagahara et al., 2021), and its PHRED-scaled CADD score, which integrates diverse information in silico, was above 20 (23.3; CADD v.1.6, Oct 2022).
Last Updated: 05 Dec 2022
- Zhou Y, Mägi R, Milani L, Lauschke VM. Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk. J Lipid Res. 2018 Oct;59(10):1987-2000. Epub 2018 Aug 3 PubMed.
- Nagahara K, Nishibukuro T, Ogiwara Y, Ikegawa K, Tada H, Yamagishi M, Kawashiri MA, Ochi A, Toyoda J, Nakano Y, Adachi M, Mizuno K, Hasegawa Y, Dobashi K. Genetic Analysis of Japanese Children Clinically Diagnosed with Familial Hypercholesterolemia. J Atheroscler Thromb. 2021 May 20; PubMed.
No Available Further Reading
- Maeda H, Nakamura H, Kobori S, Okada M, Mori H, Niki H, Ogura T, Hiraga S. Identification of human apolipoprotein E variant gene: apolipoprotein E7 (Glu244,245----Lys244,245). J Biochem. 1989 Jan;105(1):51-4. PubMed.
- Yamamura T, Yamamoto A, Sumiyoshi T, Hiramori K, Nishioeda Y, Nambu S. New mutants of apolipoprotein E associated with atherosclerotic diseases but not to type III hyperlipoproteinemia. J Clin Invest. 1984 Oct;74(4):1229-37. PubMed.
Other mutations at this position
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