TNF, NF-kB & Inflammatory Cytokines

Intergenic regulatory variant at 6q23 near TNFAIP3 whose T allele is protective against rheumatoid arthritis in Europeans, representing the second independent RA signal at this locus alongside risk variant rs6920220

Intergenic regulatory variant between TRAF1 and C5 on chromosome 9; the A allele reduces TRAF1 expression, amplifying NF-kB-driven inflammation and increasing rheumatoid arthritis risk in Europeans

Intronic variant in DBC1 (DBCCR1/BRINP1) at 9q33.1 associated with multiple sclerosis susceptibility; the common A allele increases MS risk, while the minor G allele is protective

Synonymous exon 5 variant in IL-1β that increases IL-1β protein secretion despite no amino acid change, elevating chronic periodontitis risk and modulating inflammatory disease susceptibility

Intergenic protective variant near TNFAIP3 that tags a haplotype associated with enhanced A20-mediated NF-kB suppression, reducing rheumatoid arthritis risk at the 6q23 locus

Missense variant in IL-1α (Ala114Ser) that acts as a common hypomorphic mutation — the minor Serine allele reduces IL-1α secretion by ~50% through post-translational retention; the Serine allele is associated with periodontitis susceptibility and ankylosing spondylitis in Europeans

Intronic STAT3 variant associated with increased atopic dermatitis risk (OR=1.09) via altered cytokine signaling in the JAK-STAT pathway

TNF promoter variant that disrupts an OCT-1 binding site, altering TNF-alpha transcription independently of the -308 variant; the T allele is associated with Crohn's disease susceptibility in Asian populations, psoriasis, and modified response to anti-TNF biologics

Promoter variant increasing TNF-alpha production approximately 2-fold, associated with autoimmune diseases and anti-TNF drug response

TNF promoter variant that disrupts NF-κB p50-p50 binding, reducing TNF-alpha production by ~31% and influencing susceptibility to autoimmune disease and biologic treatment response

Intronic variant in LOC100506023 (PRDX6-AS1) and TNFSF4 at the 1q25.1 locus, where the common C allele is associated with modestly increased rheumatoid arthritis risk across diverse populations

Missense variant in PTPN13 (FAP-1) converting Ile to Met at position 1522; the G allele is associated with impaired tumor-suppressive Fas-mediated apoptosis and elevated squamous cell carcinoma risk

Missense variant in the A20 ubiquitin-editing enzyme that weakens NF-kB negative feedback, increasing susceptibility to autoimmune and inflammatory diseases

Missense variant in NFKBIE (IκBε) reducing the inhibitory capacity of the IκB-epsilon protein, leading to heightened NF-κB inflammatory signaling; the G allele is associated with rheumatoid arthritis susceptibility across multiple ancestries

Promoter variant in the NFAT binding site that increases IL-17A transcription, elevating Th17-driven inflammation and autoimmune disease risk

Synonymous coding variant in the cannabinoid receptor 2 gene that tags a haplotype block influencing CB2 receptor expression in immune cells; the G allele (coding-strand C) is associated with elevated rheumatoid arthritis risk and altered endocannabinoid-mediated immune regulation

Exon 10 missense variant in the inflammasome regulator pyrin, converting methionine to isoleucine at codon 694; one of five founder FMF mutations, associated with familial Mediterranean fever and colchicine responsiveness — particularly prevalent in East Asian FMF patients and Lebanese founder lineages

3'UTR variant in IL-17A that alters post-transcriptional regulation via miRNA targeting, modulating IL-17A protein output and Th17-driven inflammatory disease susceptibility

Intronic GWAS variant in the TRAF1-C5 locus on chromosome 9 robustly associated with seropositive rheumatoid arthritis risk

Intronic STAT3 variant where the T allele (reference, ~66%) increases risk for autoimmune thyroid disease, Crohn's disease, and lung cancer

Intronic IL6R variant associated with coronary artery disease risk, elevated inflammatory markers (CRP, LDL, ApoB), and altered response to IL-6 receptor-blocking biologics (tocilizumab, sarilumab); the T allele tags a haplotype with subtly enhanced classical IL-6 signaling

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

The most common and clinically severe MEFV mutation, converting methionine to valine at codon 694 of pyrin; homozygous carriers typically develop full familial Mediterranean fever with early onset, frequent attacks, and high amyloidosis risk if untreated with colchicine

Regulatory variant upstream of TNFAIP3 that reduces A20 expression and impairs NF-kB negative feedback, increasing susceptibility to rheumatoid arthritis and multiple autoimmune diseases

Missense variant that reduces IL-17F bioactivity and acts as a natural IL-17F antagonist, protecting against Th17-driven autoimmune conditions while impairing antifungal mucosal defense

Intergenic tag SNP in the 6q23 regulatory region upstream of TNFAIP3