Immune & Gut

Tag SNP for HLA-DQ2.5 haplotype, the strongest genetic risk factor for celiac disease and associated with multiple autoimmune conditions

Tag SNP identifying HLA-DQ8 haplotype, second strongest genetic risk factor for celiac disease and major type 1 diabetes risk marker

Missense variant in Toll-like receptor 4 reducing bacterial endotoxin recognition and dampening inflammatory responses

Promoter variant affecting IL-10 production — the master anti-inflammatory cytokine that regulates immune response

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

Immune checkpoint regulatory variant in the 3'UTR affecting T-cell activation and autoimmune disease susceptibility

The strongest non-HLA autoimmune risk allele, affecting T-cell and B-cell signaling threshold

Intronic variant creating alternative splice site that increases type I interferon production and autoimmune disease risk

Missense variant in the NOD2 gene that increases Crohn's disease risk, particularly ileal disease, by impairing bacterial peptidoglycan recognition

NOD2 bacterial sensor variant that increases Crohn's disease risk by impairing immune response to gut bacteria

Autophagy gene variant affecting bacterial clearance in gut epithelial cells, strongly associated with Crohn's disease risk

Strongly protective variant against inflammatory bowel disease and other autoimmune conditions through impaired IL-23 signaling

Zinc and manganese transporter variant that reduces metal ion absorption, affecting gut barrier function and microbiome composition

Mucin-1 gene variant affecting gastric mucus barrier function and H. pylori colonization resistance

Autophagy regulator affecting bacterial clearance in the gut and Crohn's disease susceptibility

Macrophage-stimulating protein variant affecting innate immune response and IBD susceptibility

Intronic variant in the primary lymphangiogenesis growth factor gene associated with elevated lymphedema risk and impaired lymphatic vascular support

Nonsense variant eliminating filaggrin protein, the major genetic risk factor for atopic dermatitis and the atopic march from eczema to asthma and food allergy

Gain-of-function missense variant in the NLRP3 inflammasome sensor that elevates baseline IL-1beta and IL-18 production, increasing susceptibility to gout, inflammatory bowel disease, and metabolic inflammation

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

Upstream regulatory variant in TSLP reducing cytokine expression; the protective T allele lowers TSLP production 2.5-fold and is associated with reduced risk of asthma and allergic rhinitis

Promoter variant affecting CD14 expression and LPS receptor signaling — determines innate immune sensitivity to bacterial endotoxin and drives a classic gene-environment interaction with microbial exposure

Missense variant disrupting mannose-binding lectin oligomerization, reducing serum MBL 5-10-fold and impairing complement-mediated opsonization of bacteria, viruses, and fungi

Gain-of-function missense variant in the CARD9 adaptor protein that enhances antifungal immune signaling, increasing susceptibility to inflammatory bowel disease, allergic bronchopulmonary aspergillosis, and recurrent fungal infections

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

Gain-of-function missense variant in the IL-4 receptor alpha chain that amplifies Th2 immune signaling, increasing susceptibility to asthma, atopic dermatitis, and allergic disease

Missense variant in Fc gamma receptor IIIa (CD16a) that determines NK cell IgG binding affinity and antibody-dependent cellular cytotoxicity — major pharmacogenomic factor for monoclonal antibody therapy response

Intergenic variant near JAK2 that increases JAK2 expression and JAK-STAT signaling, disrupting intestinal barrier function and increasing IBD susceptibility

5' UTR variant in the beta-defensin 1 gene that reduces antimicrobial peptide expression in gut and mucosal epithelium, increasing susceptibility to colonic Crohn's disease and dental caries

Intronic variant affecting IL-2 receptor alpha chain expression and soluble IL-2RA shedding — impairs T-regulatory cell signaling and increases autoimmune disease susceptibility

Gain-of-function missense variant in the MDA5 viral RNA sensor, enhancing type I interferon production and increasing autoimmune disease risk

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

Near-gene regulatory variant tagging an IRF5 haplotype that elevates interferon production and increases risk for lupus, systemic sclerosis, Sjögren syndrome, and seropositive rheumatoid arthritis

Intronic variant in CD40 regulating B-cell surface expression; the G allele drives higher CD40 levels and is shared risk across rheumatoid arthritis, SLE, Crohn's disease, and multiple sclerosis

Tag SNP for HLA-DRB1*15:01 (physically located near HLA-DRA), the strongest genetic risk factor for multiple sclerosis, with implications for vitamin D optimization and EBV immune control

A missense variant in the IL-7 receptor alpha chain that increases soluble IL-7R production by promoting exon 6 skipping, amplifying IL-7 bioactivity and raising susceptibility to multiple sclerosis and other autoimmune diseases

Intronic variant in IL2RA intron 1 that creates an estrogen-responsive enhancer element — the risk C allele allows estrogen receptor alpha binding and increases IL2RA transcription, altering T-regulatory cell function and autoimmune disease susceptibility

Intronic variant in CD58 (LFA-3) that modulates T-cell costimulation and Treg function; the protective G allele raises CD58 expression and reduces multiple sclerosis risk

Splice-region variant in TNFR1 that generates a soluble Δ6 isoform mimicking anti-TNF drugs, conferring MS risk and explaining why TNF blockers worsen demyelinating disease

Tag SNP for HLA-C*06:02, the strongest genetic risk factor for psoriasis, determining disease phenotype and predicting differential response to biologic therapy

Intronic ERAP1 variant that increases expression, raising psoriasis risk specifically in HLA-C*06:02 carriers through enhanced autoantigen trimming

Near-HLA-C intergenic variant that tags HLA-C*06:02 haplotype, conferring risk for early-onset psoriasis vulgaris through MHC class I antigen presentation

Missense variant in Act1 that abolishes IL-17 signaling by disrupting TRAF6 binding, driving paradoxical hyperactivation of Th17 responses and psoriasis susceptibility

Near-gene variant at the IL12B locus associated with psoriasis risk through altered expression of the p40 subunit shared by IL-12 and IL-23 cytokines

Intronic variant in Complement Factor B associated with strongly elevated systemic lupus erythematosus risk through alternative complement pathway dysregulation

Intronic STAT4 variant that amplifies the interferon-alpha and IL-12 response, conferring the strongest common genetic risk for lupus outside the HLA region

BANK1 scaffold protein missense variant that shifts B-cell receptor signaling toward hyperactivation, increasing risk for systemic lupus erythematosus and other B-cell-driven autoimmune diseases

Missense variant in Toll-Like Receptor 2 impairing innate immune signaling to gram-positive bacteria and mycobacteria, increasing susceptibility to tuberculosis, sepsis, and staphylococcal infections

Intronic variant in IFNL4 — the strongest host genetic predictor of hepatitis C spontaneous clearance and treatment response, controlling interferon lambda antiviral immunity

Missense variant in EVI5's coiled-coil domain altering immune cell trafficking and multiple sclerosis susceptibility

Causal frameshift polymorphism controlling IFNL4 protein production; the ΔG allele creates functional interferon lambda 4 which paradoxically impairs hepatitis C clearance

Regulatory variant in the 5' UTR of DDX39B (RNA helicase/mRNA export factor) that reduces DDX39B translation, impairing IL7R exon 6 inclusion and increasing soluble IL7R — the strongest known epistatic interaction in MS genetics

Regulatory variant upstream of BLK that reduces B-lymphoid tyrosine kinase expression, impairing B-cell tolerance and raising risk for SLE, Sjögren's syndrome, systemic sclerosis, and rheumatoid arthritis

Missense variant in IFNL4 exon 2 that reduces IFN-λ4 protein activity; the Ser70 form (A allele) produces weaker antiviral signalling and is associated with better hepatitis C clearance among ΔG carriers