Intronic ELMO1 variant acting as an eQTL that modulates engulfment and cell motility protein expression in thymic and peripheral immune cells, with GWAS associations with celiac disease, primary biliary cholangitis, and inflammatory bowel disease

Regulatory CpG-SNP downstream of SH2B1 that reduces gene expression via allele-specific methylation, impairing leptin and insulin signaling and increasing NAFLD severity and insulin resistance risk

Missense variant in CPT2 that destabilizes the carnitine palmitoyltransferase 2 enzyme, impairing mitochondrial uptake of long-chain fatty acids and causing recurrent exercise- and fever-induced rhabdomyolysis in homozygotes; the most common cause of adult myopathic CPT II deficiency in Europeans.

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

Pathogenic missense variant in glucokinase that raises the glucose set-point for insulin secretion, causing mild stable fasting hyperglycemia (heterozygous MODY2) or severe permanent neonatal diabetes (homozygous)

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