IBD & Mucosal Immunity

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

Rare NOD2 missense variant (Ser431Leu) that reduces NF-κB activation in response to bacterial muramyl dipeptide, independently associated with Crohn's disease risk; often co-inherited on a haplotype with the V793M variant

Rare NOD2 missense variant (Val793Met) identified in IBD deep-resequencing; contributes to Crohn's disease risk primarily in compound heterozygous state with other NOD2 variants

Rare NOD2 missense variant (Asn852Ser) that impairs innate immune sensing of bacterial peptidoglycan and is associated with Crohn's disease risk; markedly enriched in Ashkenazi Jewish populations (~1.6%)

Intronic IL23R variant in LD block 2 where the T allele is associated with increased susceptibility to Crohn's disease and ankylosing spondylitis while the C allele is protective — a signal distinct from the rs1004819/rs7517847 haplotype block

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

3' UTR and intronic IL23R variant disrupting Let-7e/Let-7f miRNA binding — the A allele elevates IL-23 receptor expression and is associated with ankylosing spondylitis, inflammatory bowel disease, and rheumatoid arthritis susceptibility; the C allele was independently associated with Graves' ophthalmopathy in a Caucasian cohort

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

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 IL23R variant whose minor T allele tags a protective haplotype that dampens IL-23/Th17 signalling, reducing susceptibility to Crohn's disease and ulcerative colitis

Intronic IL23R variant in strong linkage disequilibrium with the functional R381Q variant (rs11209026); the minor G allele tags the protective haplotype that dampens IL-23 receptor signalling, reducing risk for ankylosing spondylitis, Crohn's disease, ulcerative colitis, and psoriasis

Regulatory variant upstream of the IL-23 receptor gene more strongly associated with psoriatic arthritis than cutaneous psoriasis alone, implicating distinct Th17 signaling at the joint versus skin interface

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

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

Intronic IL23R variant whose minor A allele tags the protective haplotype for ankylosing spondylitis and Crohn's disease while representing an independent susceptibility signal for rheumatoid arthritis

Intergenic variant between IL23R and IL12RB2 on chromosome 1p31.3 associated with increased risk of ankylosing spondylitis, Behçet's disease, and Crohn's disease through IL-23 pathway dysregulation

Promoter variant in the beta-defensin 1 gene that reduces constitutive hBD-1 expression, altering mucosal antimicrobial defense and susceptibility to inflammatory and infectious conditions

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

The most important Crohn's disease risk variant worldwide — a frameshift insertion in NOD2 that abolishes bacterial muramyl dipeptide sensing; homozygotes face 20–40x elevated Crohn's risk

Near-gene regulatory variant that reduces MUC1 mucin expression on the gastric epithelium, impairing mucosal barrier defense and increasing susceptibility to diffuse-type gastric cancer

MTX1 intronic variant at 1q22 tagging a gastric cancer susceptibility locus that regulates mucosal integrity via the MUC1/UBAP2L axis

Intronic ATG16L1 variant in tight LD with the T300A coding variant; the G risk allele tags a haplotype that sensitizes the ATG16L1 protein to caspase-3-mediated degradation, impairing autophagy and Paneth cell antimicrobial function, raising risk for Crohn's disease

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

Regulatory variant in the PSCA 5′ UTR that recruits the repressor YY1 to the promoter, suppressing PSCA expression in gastric epithelium and increasing susceptibility to diffuse-type gastric cancer and gastric mucosal atrophy

Intronic variant in FGFR1OP (CEP43) at the RNASET2-FGFR1OP-CCR6 autoimmune susceptibility locus, with the T allele increasing risk for Crohn's disease, rheumatoid arthritis, and related autoimmune conditions

Promoter variant in SLC22A5 (OCTN2) that reduces carnitine transporter expression and forms part of the IBD5 two-locus TC haplotype strongly associated with Crohn's disease susceptibility

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

Intronic IL12RB2 variant associated with IL-12 signaling pathway variation and susceptibility to Th1-mediated autoimmune conditions including primary biliary cholangitis, allergic rhinitis, and endometriosis

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

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

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

A synonymous FUT2 proxy variant in strong LD with the W143X nonsense allele (rs601338), tagging secretor status and associated with Crohn's disease susceptibility, psoriasis risk, and gut microbiome composition; the G allele marks the secretor phenotype

Intronic IRGM variant that impairs autophagy-mediated clearance of intracellular bacteria, raising risk for Crohn's disease — particularly ileal disease and fistulizing complications

Intronic FUT2 proxy variant tagging secretor status — whether ABO blood group antigens are secreted into body fluids; influences human milk oligosaccharide composition, infant gut microbiome colonisation, and mucosal immunity

Intronic IL23R variant where the minor T allele is associated with increased ankylosing spondylitis susceptibility and the common C allele confers protection across several IL-23/Th17-driven inflammatory diseases in Asian populations

Promoter variant in the PTGS2/COX-2 gene that reduces baseline COX-2 expression, increasing susceptibility to ulcerative colitis and modifying colorectal cancer and cardiovascular risk

Intronic variant in CDKAL1, a tRNA methylthiotransferase gene; the C allele is associated with increased risk of Crohn's disease and shared pleiotropic risk for psoriasis through immune cell expression of CDKAL1

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

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

Missense variant in the IL-23 receptor that substitutes leucine for proline at position 310; the rare leucine allele (T) is associated with susceptibility to Graves' disease and rheumatoid arthritis through altered IL-23/Th17 immune signaling