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

Synonymous variant in TLR9 that increases receptor expression, amplifying innate immune responses to bacterial and viral DNA via CpG motif recognition

Near-gene variant tagging an IRF5 protective haplotype in the 5' promoter region that reduces type I interferon output and lowers susceptibility to lupus, rheumatoid arthritis, and related autoimmune conditions

Frameshift deletion eliminating filaggrin protein, the second most common European FLG null allele — causes ichthyosis vulgaris and atopic dermatitis, and together with R501X enables complete filaggrin deficiency in compound heterozygotes

Missense variant in Toll-like receptor 4 that co-segregates with Asp299Gly on the same haplotype, together reducing LPS-driven innate immune signaling and altering gram-negative bacterial recognition

Promoter variant in the IL-10 haplotype system — regulates IL-10 anti-inflammatory cytokine production capacity

Missense variant in TNF receptor 1 that causes low-penetrance TRAPS (recurrent fever syndrome) and independently raises multiple sclerosis risk ~1.6-fold via stronger TNF binding and altered receptor trafficking

Missense variant in TLR3 that halves dsRNA-binding capacity, reducing antiviral interferon responses and increasing susceptibility to several viral infections

Intronic variant in the IL-23 receptor gene associated with increased risk of psoriasis, psoriatic arthritis, Crohn's disease, and ankylosing spondylitis through altered IL-23 signaling and Th17 cell activation

Missense variant in complement component C2 forming a protective haplotype with CFB that reduces age-related macular degeneration risk by ~45-50%

Intronic variant in the HLA class III region near MSH5 associated with lupus susceptibility, IFN-α regulation, and epistatic interactions with IRF5 and CTLA4

Coding variant replacing isoleucine with serine at TLR1 position 602, disrupting a transmembrane trafficking motif and preventing TLR1 from reaching the cell surface — reducing TLR1/TLR2 heterodimer signaling in response to bacterial triacylated lipopeptides

BANK1 ankyrin-domain missense variant that amplifies B-cell receptor signaling through altered protein-protein interactions; the G allele (Ala383) confers risk for lupus, rheumatoid arthritis, and systemic sclerosis, with RA risk requiring epistatic co-presence of BLK rs13277113

Intergenic variant upstream of IFNL3 — second major IL28B locus predictor of hepatitis C spontaneous clearance and treatment response, with independent predictive value over rs12979860 in Asian populations

Missense variant (Arg127Pro) in ERAP1 that subtly alters ER peptide trimming kinetics, increasing autoimmune risk for psoriasis and ankylosing spondylitis particularly in individuals carrying HLA-C*06:02 or HLA-B27; association is strongest for disease onset in adolescence

Missense variant reducing ERAP1 aminopeptidase activity, increasing ankylosing spondylitis and psoriasis risk through altered MHC class I peptide trimming — effect contingent on HLA-B27 and HLA-C*06:02 carrier status

Synonymous variant in Toll-Like Receptor 2 affecting mRNA stability and splicing, associated with pulmonary tuberculosis susceptibility, cancer risk modification, and anti-TNF treatment response in inflammatory bowel disease

Intergenic eQTL near HLA-DQA1 that tags the DR15 haplotype (DRB1*15:01/DQA1*01:02/DQB1*06:02), the strongest genetic risk factor for multiple sclerosis, and is also associated with SLE and ulcerative colitis

Intronic CD58 variant in strong LD with rs2300747 (r²=0.929); the C allele drives MS susceptibility (OR 2.22 for CC) and predicts poor IFN-beta therapy response — the pharmacogenomic dimension absent from its LD partner

Kozak sequence variant at position −1 of the CD40 start codon — the C allele boosts translational efficiency, producing ~30% more CD40 protein and increasing susceptibility to Graves' disease; the T allele reduces CD40 expression and independently elevates risk for multiple sclerosis and Crohn's disease

Intronic variant in the TRAF3IP2 locus that lies within the antisense lncRNA TRAF3IP2-AS1 and amplifies IL-17 pathway dysregulation; the G allele is a gain-of-function mutation enhancing SRSF10 recruitment that suppresses IRF1-driven Act1 transcription; the G allele independently associates with psoriasis (OR=1.69) and co-occurs on a secondary risk haplotype (OR=1.8) alongside the primary risk haplotype carrying rs13210247_A (OR=2.7)

Missense variant in the IL-17 adaptor Act1 (Arg74Trp) that is the primary GWAS hit for psoriatic arthritis at the TRAF3IP2 locus (OR=1.83, P=8.56×10⁻¹⁷); in strong LD with the functional D10N variant but appears to tag a partially overlapping, PsA-enriched haplotype

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

Missense variant in the TLR2/TLR4 adaptor protein Mal that modulates innate immune signaling strength, conferring broad infectious disease protection in heterozygous carriers

Coding variant replacing serine with proline at TLR6 position 249, altering TLR2/TLR6 heterodimer signaling intensity for diacylated lipopeptides from bacteria and mycoplasma — Pro249 confers stronger NF-κB activation while Ser249 reduces TLR2/TLR6-mediated inflammation, with consequences for leprosy susceptibility, cardiovascular risk, and upper genital tract infections

Missense variant in the CTLA-4 leader peptide that reduces surface expression of this immune checkpoint receptor, increasing T cell activity and autoimmune disease risk

Intronic C2 variant forming the H7 protective haplotype with CFB R32Q, reducing classical complement activation and cutting AMD risk by roughly half

Intronic IL10 variant that reduces anti-inflammatory cytokine production, independently raising susceptibility to gut inflammation, H. pylori infection, and asthma severity

Intronic IL23R variant in which the T allele increases susceptibility to Crohn's disease, ulcerative colitis, and ankylosing spondylitis, while the G allele is protective — independent of the rs2201841 risk signal at the same locus

Intronic IL-23 receptor variant that increases susceptibility to ankylosing spondylitis and inflammatory bowel disease by enhancing IL-23/Th17 inflammatory signaling

Promoter variant that alters transcription factor binding and TLR9 expression, affecting innate immune responses to bacterial and viral CpG DNA across infections, autoimmunity, and transplant outcomes

Enhancer variant ~5 kb upstream of IRF5 that promotes ZBTB3-mediated chromatin looping to the IRF5 alternative promoter, driving overexpression of IRF5-short transcripts and increasing risk for lupus, Sjögren's syndrome, inflammatory bowel disease, and other autoimmune conditions; the leading causal candidate for the 5' IRF5 risk signal and a tag for the CGGGG promoter insertion that creates an extra Sp1 binding site

Frameshift deletion in the third filaggrin repeat domain — the third most common European FLG null allele, causing filaggrin haploinsufficiency in carriers and complete filaggrin deficiency in compound heterozygotes with R501X or 2282del4

Nonsense variant eliminating filaggrin protein — a minor European FLG null allele that acts as a compound heterozygote partner to the major European FLG mutations in atopic dermatitis and ichthyosis vulgaris

Promoter variant in Toll-Like Receptor 2 that increases TLR2 expression, associated with atopic dermatitis severity, psoriasis susceptibility, and modulated innate immune responses to bacterial and fungal ligands