Promoter variant in the GRIN2B Sp1 binding site that reduces NR2B subunit expression, lowering NMDA receptor activity critical for learning and memory

ENPP1 K121Q variant that increases ENPP1 binding affinity to the insulin receptor by 2–3 fold, blunting insulin signaling and raising insulin resistance risk.

Synonymous variant in P-glycoprotein affecting drug efflux pump expression and hundreds of substrate drugs

Pathogenic missense variant abolishing 17α-hydroxylase/17,20-lyase activity, causing combined cortisol and sex steroid deficiency with mineralocorticoid excess

Phase I detoxification enzyme that activates polycyclic aromatic hydrocarbons and metabolizes estrogens; the Val variant increases catalytic activity, producing more reactive intermediates

Missense variant in alpha-dystrobrevin disrupting the EF-hand calcium-binding domain, associated with left ventricular noncompaction cardiomyopathy in a single Japanese family

Intronic IL23R variant in LD block 2 where the T allele is associated with increased susceptibility to Crohn's disease and ankylosing spondylitis while the C allele is protective — a signal distinct from the rs1004819/rs7517847 haplotype block

Rare stop-gain variant in BMPR2 (p.Trp466Ter) that truncates the kinase domain via nonsense-mediated decay, causing haploinsufficiency and hereditary pulmonary arterial hypertension with incomplete penetrance and sex-dependent expression

Intronic variant in the PRG3 gene encoding eosinophil major basic protein homologue (MBPH/MBP-2) at chromosome 11q12.1; the rarer C allele tags variation in PRG3 expression and is associated with altered eosinophil granule protein activity implicated in allergic inflammation, IgE-mediated tissue damage, and atopic disease susceptibility

Promoter variant in Toll-like receptor 4 that drives higher TLR4 expression and amplified innate immune signaling, increasing risk for atherosclerosis, diabetic retinopathy, and inflammatory tissue damage