Intronic variant in FOXO1, a pro-apoptotic transcription factor whose suppression by the AKT/progestin pathway promotes uterine fibroid cell survival; the G allele is associated with elevated uterine leiomyoma risk in multiple GWAS, while the A allele associates with later age at natural menopause.

Missense variant in the endothelial protein C receptor gene that increases EPCR shedding, paradoxically raising plasma protein C levels while reducing endothelial anticoagulant activity and increasing VTE risk

Promoter variant that selectively increases IL-13 expression in Th2 lymphocytes, amplifying the central Th2 cytokine driving asthma, atopic dermatitis, elevated total IgE, and mucus hypersecretion; the T allele creates a Yin-Yang 1 binding site that attenuates STAT6-mediated repression of IL-13 transcription

Phase II detoxification - acetylation of aromatic amines and certain medications

Hypomorphic missense variant in the TMPRSS3 serine protease catalytic domain; the most common TMPRSS3 pathogenic allele worldwide, causing DFNB8 progressive or DFNB10 congenital hearing loss depending on the second allele; a founder mutation in Korean, Chinese, Dutch, and German populations

Intronic variant in CYP3A4 intron 10 that upregulates a suppressive lncRNA, reducing CYP3A4 and CYP3A5 expression by ~30%; affects dosing of tacrolimus, sirolimus, statins, and psychiatric drugs

Missense variant in the GIP incretin hormone that changes its bioactivity and serum stability, with the derived Gly allele showing higher receptor activation and positive selection in Eurasian populations

Promoter variant in APOC3 disrupting insulin-responsive regulation of apolipoprotein C-III, raising triglycerides and VLDL through impaired post-meal suppression of apoCIII secretion

Intronic variant affecting cortical bone thickness, bone mineral density, and fracture risk

Pathogenic DSP nonsense variant creating a premature stop codon at position 160 (p.Arg160Ter), causing desmoplakin haploinsufficiency and desmoplakin-associated arrhythmogenic cardiomyopathy with predominantly left ventricular fibrosis