| Chromosomal Locus | Gene(s) | Function/Role | Evidence Source |
|---|---|---|---|
| 5q22 | **TSLP**, **WDR36** | **TSLP** encodes thymic stromal lymphopoietin, an epithelial alarmin that promotes allergic/Th2 polarization, activates dendritic cells and ILC2s, and is strongly implicated in EoE initiation; **WDR36** is co-localized at the susceptibility locus and repeatedly recovered in GWAS/OpenTargets associations. This is one of the most reproducible EoE loci. | Established locus in GWAS and reviews (pqac-00000002, pqac-00000003, pqac-00000004, pqac-00000005, pqac-00000000) |
| 2p23 | **CAPN14** | Encodes calpain-14, an esophagus-enriched protease induced by IL-13; contributes to epithelial barrier dysfunction, desmosomal destabilization, and EoE-specific epithelial remodeling. One of the most disease-specific EoE loci. | Established locus in GWAS and mechanistic studies (pqac-00000002, pqac-00000003, pqac-00000004, pqac-00000005, pqac-00000000) |
| 11q13 | **LRRC32**, **C11orf30/EMSY** | Associated with epithelial and immune regulation; repeatedly identified across EoE genetic studies and also linked to broader atopic susceptibility. Often cited as a reproducible shared atopy/EoE locus. | Established locus in GWAS/meta-analysis (pqac-00000002, pqac-00000003, pqac-00000005) |
| 12q13 | **STAT6** | Central transcription factor downstream of IL-4/IL-13 signaling; regulates Th2 effector programs and eosinophilic inflammation. Variants may also influence treatment-related phenotypes such as PPI response. | Established locus and functional relevance in EoE (pqac-00000002, pqac-00000004) |
| 16p13 | **CLEC16A**, **DEXI** | Reproducible susceptibility region identified in more recent genetic studies/meta-analyses; likely contributes to immune regulation and shared atopic disease architecture rather than being EoE-exclusive. | Reproducible susceptibility locus in recent reviews/meta-analysis (pqac-00000003, pqac-00000007) |
| 15q23 | **SMAD3** | Encodes a key mediator of TGF-β signaling, linking genetic susceptibility to remodeling/fibrostenotic biology and tissue fibrosis in EoE. | Additional genome-wide significant locus from newer GWAS/meta-analysis (pqac-00000003, pqac-00000004) |
| Additional validated/implicated loci | **DSG1**, **DSP**, **FLG** and other barrier genes | Not always the lead GWAS locus in summary tables, but repeatedly implicated as susceptibility or familial-risk genes affecting epithelial integrity, allergen penetration, and barrier failure. | Barrier-gene evidence from human genetics and mechanistic reviews (pqac-00000005, pqac-00000006) |
| Recent GWAS expansion | 8 risk loci with 11 independent variants in EoE GWAS | Newer analyses expanded the map beyond the classic loci, identifying additional signals including loci near **GATA3** and **IL4R**, reinforcing overlap with type 2 immunity and atopic disease genetics. | Expanded GWAS findings (pqac-00000007, pqac-00000008) |
| Recent MTAG expansion | 24 loci; ~90 candidate genes | Multi-trait analysis with related atopic diseases substantially expanded susceptibility architecture to **24 loci** with **90 candidate genes**, showing shared genetic basis with asthma, allergic rhinitis, and atopic dermatitis, and supporting polygenic risk modeling. | MTAG expansion/preprint summary (pqac-00000007, pqac-00000008) |


*Table: This table summarizes the main established and newly expanded genetic susceptibility loci for eosinophilic esophagitis, emphasizing how classic barrier and type 2 immunity genes have been extended by recent GWAS/MTAG analyses to a broader polygenic architecture.*