Research ArticleKidney Disease

Kidney disease genetic risk variants alter lysosomal beta-mannosidase (MANBA) expression and disease severity

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Science Translational Medicine  13 Jan 2021:
Vol. 13, Issue 576, eaaz1458
DOI: 10.1126/scitranslmed.aaz1458

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A glycosidase and kidney disease

Genetic variants on chromosome 4 have been linked to kidney disease by previous genome-wide association studies. Gu et al. now show these loci alter beta mannosidase (MANBA) expression and modulate of chronic kidney disease (CKD) risk. Genetic and phenotypic analyses showed that MANBA loss of function associated with CKD risk and severity in humans. Mouse models with heterozygous and homozygous loss of MANBA functionally validated the role of Manba in kidney disease susceptibility. Mechanistically, reducing Manba expression in kidney tubule cells affected lysosomal structure and function and induced inflammation and fibrosis, suggesting that lysosomal dysfunction plays a role in CKD.

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