Mature Protein Numbering: R180C

Other Names: ApoE1 Baden


Clinical Phenotype: Hyperlipoproteinemia Type IV, Blood Lipids/Lipoproteins
Reference Assembly: GRCh37/hg19
Position: Chr19:45412145 C>T
Transcript: NM_000041; ENSG00000130203
dbSNP ID: rs1426426514
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CGC to TGC
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4


This variant was identified in a 42-year-old German woman with type IV hyperlipidemia, having high levels of triglycerides and moderately elevated levels of cholesterol in blood (Hoffman et al., 2001). Isoelectric focusing of her ApoE protein, revealed two bands: one migrating to the position of the common ApoE isoform ApoE3, and a faster-migrating band, ApoE1. Using restriction endonuclease and DNA sequence analyses, the authors identified the mutation and inferred its backbone isoform was R176C (APOE2), consistent with the observation of the ApoE1 migrating band. Based on isoelectric focusing analyse, only one carrier was identified in a cohort of 5000 Caucasian individuals.

The proband’s brother also carried the variant and had high levels of both triglycerides and cholesterol. Neither of the proband’s two sons carry the variant and they both had normal triglyceride levels. The mother was also a non-carrier, and the father’s genotype was unknown.

A single heterozygote of African ancestry was reported in the gnomAD variant database (v2.1.1, May 2022).

Biological effect

The biological effect of this mutation is unknown. The authors suggested it may inhibit the hydrolysis of triglycerides associated with very low-density lipoproteins (VLDL) (Hoffman et al., 2001).

One study predicted R198 forms part of an amphipathic α-helix, with three arginines, including R198, clustered at its polar-nonpolar interface. This helix may play a role in linking lipid binding to subsequent receptor binding. It has been proposed to interact with phospholipid head groups which may facilitate interaction of one of the other arginines, R190, with the ligand-binding region of the LDL receptor (Morrow et al, 2000).

Of note, a synthetic variant at the same position, R198A, showed a slightly higher binding activity compared with ApoE3 control protein. R198A’s affinity was 129 percent that of ApoE3 in an assay in which ApoE particles loaded with the synthetic lipid DMPC competed for binding of labeled LDL on the surface of cultured fibroblasts (Morrow et al, 2000).

This variant's PHRED-scaled CADD score, which integrates diverse information in silico, was above 20, suggesting a deleterious effect (CADD v.1.6, May 2022).

Nomenclature Notes

This variant’s encoded protein was named ApoE1 Baden. ApoE1 refers to the protein’s isoelectric migration, beyond ApoE2, and Baden refers to the southwestern part of Germany where the proband hailed from.

Last Updated: 05 Dec 2022


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Mutations Citations

  1. APOE R176C (ApoE2)

Paper Citations

  1. . Apolipoprotein E1 Baden (Arg(180)-->Cys). A new apolipoprotein E variant associated with hypertriglyceridemia. Clin Chim Acta. 2001 Jan;303(1-2):41-8. PubMed.
  2. . Effect of arginine 172 on the binding of apolipoprotein E to the low density lipoprotein receptor. J Biol Chem. 2000 Jan 28;275(4):2576-80. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Apolipoprotein E1 Baden (Arg(180)-->Cys). A new apolipoprotein E variant associated with hypertriglyceridemia. Clin Chim Acta. 2001 Jan;303(1-2):41-8. PubMed.

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