Intronic CYP3A4 variant associated with altered drug clearance, affecting metabolism of methadone, cyclosporine, and other CYP3A4 substrates

Regulatory variant in a core clock gene that influences circadian timing, sleep-wake preference, and reward processing

Intronic variant in IGFBP3 — the gene encoding the main carrier protein for IGF-1 in circulation — associated with lower circulating IGFBP-3 levels in carriers of the G allele

Promoter variant 2 kb upstream of FABP1 (liver fatty acid binding protein) that reduces transcriptional activity; the T allele lowers hepatic FABP1 expression, altering liver fatty acid uptake and increasing risk of dyslipidemia and impaired hepatic lipid handling

Intronic NR3C1 variant with TT genotype enriched in Polish centenarians; C allele associated with elevated cholesterol in the oldest-old

Pathogenic stop-gain in desmoplakin's tail domain; one copy truncates the protein by 1,062 amino acids, disrupting desmosomal junctions in the heart and causing arrhythmogenic cardiomyopathy with left ventricular predominance

Intronic variant in the PGC-1alpha gene linked to population-specific type 2 diabetes risk and mitochondrial biogenesis regulation

Coding variant replacing serine with proline at TLR6 position 249, altering TLR2/TLR6 heterodimer signaling intensity for diacylated lipopeptides from bacteria and mycoplasma — Pro249 confers stronger NF-κB activation while Ser249 reduces TLR2/TLR6-mediated inflammation, with consequences for leprosy susceptibility, cardiovascular risk, and upper genital tract infections

Intronic variant in the SVCT2 tissue vitamin C transporter — associated with differences in plasma vitamin C levels in the EPIC cohort

Pathogenic APOB splice acceptor variant causing familial hypobetalipoproteinemia — heterozygous carriers have ~50% lower LDL-C and apoB, conferring cardiovascular protection but requiring liver and fat-soluble vitamin monitoring