rs429358 — APOE APOE4 (Cys112Arg)
Risk factor · ~14% global allele frequency
rs429358 defines the APOE4 allele through a cysteine-to-arginine substitution at position 112. It is the strongest common genetic risk factor for late-onset Alzheimer's disease, increasing risk 3-fold per allele (up to 12-fold for homozygotes).
Molecular Mechanism
APOE4 alters lipid transport in the brain, promotes amyloid-beta aggregation, disrupts blood-brain barrier integrity, and impairs synaptic plasticity. The arginine at position 112 changes the protein's lipid-binding preference and receptor interactions.
Peptide Therapeutic Relevance
HDL-mimetic peptides (e.g., 4F) and APOE-targeting peptides (e.g., CS6253) are under preclinical investigation. PepFold generates candidates targeting APOE functional domains with predicted 3D structures and synthesis protocols.
Gene: APOE (Apolipoprotein E)
Lipid transport, cholesterol metabolism, neuronal repair, and amyloid-beta clearance in the brain. APOE is the major genetic risk modulator for late-onset Alzheimer's disease.
Chromosome 19q13.32
Condition: Alzheimer's Disease
The most common neurodegenerative disease, characterized by progressive memory loss, cognitive decline, and amyloid-beta plaque accumulation. Genetic factors account for 60-80% of risk, with APOE4 being the strongest common risk allele.
Prevalence: ~50 million worldwide, projected 150 million by 2050
Related Variants
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