Second intronic enhancer variant in SMAD3 that modulates TGF-beta effector signaling in regulatory T cells, influencing susceptibility to autoimmune and inflammatory conditions including IBD and ankylosing spondylitis

Intronic risk variant within TNFAIP3 intron 2 that independently increases susceptibility to rheumatoid arthritis and SLE through a distinct LD block from the nearby intergenic 6q23 signals, completing the three-signal risk model at the TNFAIP3 locus

Nonsense mutation creating a premature stop codon at position 1853 of von Willebrand factor; homozygotes develop severe type 3 VWD with essentially absent VWF and require factor replacement, while heterozygotes typically have mild type 1 VWD

Missense variant in PCSK1 encoding an Asn221Asp substitution near the Ca-1 calcium binding site of prohormone convertase 1/3 (PC1/3); impairs catalytic activity by approximately 10%, reducing cleavage of proinsulin to insulin, POMC to alpha-MSH, and proglucagon to GLP-1; the strongest functionally-characterized common PCSK1 coding variant, with OR 1.15 for obesity in meta-analysis of over 331,000 individuals across multiple ethnic groups

Intergenic 6q25.1 variant between CCDC170 and ESR1; the C allele is an eQTL for CCDC170 expression and is associated with breast cancer risk, bone density, and estrogen-sensitive tissue proliferation

Upstream regulatory variant ~60 kb 5' of IL12B, forming the canonical two-SNP psoriasis risk haplotype with rs3212227 (3'-UTR); C allele elevates IL-12/IL-23 p40 expression, increasing psoriasis, psoriatic arthritis, and IBD susceptibility

Intronic PTPN2 variant that reduces expression of T-cell protein tyrosine phosphatase (TC-PTP), lowering the threshold for JAK/STAT-driven T-cell activation and increasing susceptibility to Crohn's disease, rheumatoid arthritis, and juvenile idiopathic arthritis

Pathogenic missense variant in CYP17A1 disrupting the heme-binding region of the enzyme, abolishing both 17α-hydroxylase and 17,20-lyase activity; the most common CYP17A1 mutation in East Asian populations (Chinese, Japanese, Korean); homozygotes develop combined 17α-hydroxylase/17,20-lyase deficiency with cortisol deficiency, sex steroid absence, and mineralocorticoid excess causing hypertension

Intronic variant in the major renal urate transporter GLUT9; the G allele reduces renal urate excretion, raising serum uric acid and increasing gout risk, with stronger effects in women than men

Synonymous C3 variant associated with reduced serum complement C3 levels and increased risk for systemic lupus erythematosus through impaired complement-mediated immune complex clearance