APOE c.-279G>A


Clinical Phenotype: Hyperlipoproteinemia Type IIb
Reference Assembly: GRCh37/hg19
Position: Chr19:45408843 G>A
Transcript: NM_000041; ENSG00000130203
Coding/Non-Coding: Non-Coding
DNA Change: Substitution
Reference Isoform: APOE Isoform 1
Genomic Region: 2kb upstream


This variant, located in the promoter region of the APOE gene, was identified in a French patient in a cohort of nearly 6,000 unrelated individuals with primary dyslipidemia (Abou Khalil et al., 2022). The carrier had elevated triglycerides in blood and was diagnosed with familial combined hyperlipidemia, also known as hyperlipoproteinemia type IIb. The carrier had a family history of dyslipidemia and their APOE genotype was APOE3/E4.

The variant was absent from the gnomAD variant database (gnomAD v3.1.1, Nov 2021).

Biological Effect

The biological effect of this variant is unknown, but it is in the APOE promoter within a region (-366 to -246) that contains enhancer-like elements (Paik et al., 1988). It is also within the HuC functional domain (-366 to -101) which acted as a negative regulatory element in a reporter assay using uninduced human neuronal cells and as a positive regulatory element in uninduced human glial cells (Maloney et al., 2007). Interestingly, the corresponding mouse sequence (which did not overlap completely with the human sequence) had no apparent effect in neuronal cells and a negative effect in glial cells.

This variant's PHRED-scaled CADD score (5.68), which integrates diverse information in silico, was below 20, a commonly used threshold to predict deleteriousness (Abou Khalil et al., 2022).

Last Updated: 05 Dec 2022


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Paper Citations

  1. . APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia. Int J Mol Sci. 2022 May 21;23(10) PubMed.
  2. . Identification and characterization of transcriptional regulatory regions associated with expression of the human apolipoprotein E gene. J Biol Chem. 1988 Sep 15;263(26):13340-9. PubMed.
  3. . Important differences between human and mouse APOE gene promoters: limitation of mouse APOE model in studying Alzheimer's disease. J Neurochem. 2007 Nov;103(3):1237-57. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia. Int J Mol Sci. 2022 May 21;23(10) PubMed.

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