Uromodulin (UMOD) is unusual among monogenic kidney disease genes defined to date in that genetic variation causes both rare, Mendelian phenotypes as well as contributing to common, complex phenotypes. Coding variants in UMOD cause autosomal dominant lubulointerstitial kidney disease ADTKD-UMOD; also called medullary cystic kidney disease type 2 (MCKD2). ADTKD-UMOD presents with slowly progressive kidney dysfunction, often accompanied by hyperuri-cemia and gout, that culminates in end-stage renal disease (ESRD). Noncoding mutations in the UMOD promoter are the most consistently replicated associations from genome-wide association studies of overall renal function in chronic kidney disease (1,5, 8).
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