GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301653/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301653GEOGSEfalseSingle-allele nanoscale mapping of regulatory variants [Micro-C]Millions of genetic variants are linked to human disease but identifying underlying mechanisms is challenging because most variants lie within the non-coding genome. We developed a Micro Capture-C variant-to-function platform (MCCv) based on analysis of single-allele chromatin structure. This can identify changes in nanoscale chromatin architecture and link variants in cis-regulatory elements to associated genes. Furthermore, MCCv can phase other heterozygous variants within a locus to link regulatory variants to allelically imbalanced gene expression and directly read out variant effects on chromatin interactions following genome editing. With this approach, we investigated 405 cis-regulatory elements linked to immune-mediated inflammatory disease in CD4+ T cells. We uncover a previously undescribed gain-of-function mechanism, which increases risk of autoimmunity through creation of a neo-CTCF motif that blocks super-enhancer contacts with the SESN3 promoter. We show SESN3 regulates mammalian target of rapamycin (mTOR) by sensing tryptophan and demonstrate its role in autoimmunity using mouse models.2026/07/26GSE301653GSM9086966GSM9086968GSM908696734281301653Homo sapiens