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

Author:

Gu Xiangchen12ORCID,Yang Hongliu13ORCID,Sheng Xin1ORCID,Ko Yi-An1,Qiu Chengxiang1ORCID,Park Jihwan1ORCID,Huang Shizheng1ORCID,Kember Rachel4ORCID,Judy Renae L.5,Park Joseph46ORCID,Damrauer Scott M.57,Nadkarni Girish8910,Loos Ruth J. F.9ORCID,My Vy Thi Ha9ORCID,Chaudhary Kumardeep9ORCID,Bottinger Erwin P.910ORCID,Paranjpe Ishan9ORCID,Saha Aparna9ORCID,Brown Christopher6ORCID,Akilesh Shreeram11ORCID,Hung Adriana M.1213ORCID,Palmer Matthew14,Baras Aris15,Overton John D.15ORCID,Reid Jeffrey15ORCID,Ritchie Marylyn46ORCID,Rader Daniel J.146,Susztak Katalin16ORCID

Affiliation:

1. Department of Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2. Division of Nephrology, Yueyang Hospital of Integrative Traditional Chinese and Western Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.

3. Division of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China.

4. Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

5. Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

6. Department of Genetics Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

7. Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA.

8. Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

9. The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

10. The Hasso Plattner Institute of Digital Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

11. Department of Pathology, University of Washington, Seattle, WA 98195, USA.

12. Nashville VA Medical Center, Nashville, TN 37212, USA.

13. Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

14. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

15. Regeneron Genetics Center (RGC), 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.

Abstract

MANBA is a kidney disease risk gene that alters tubular endolysosomal function, inducing inflammasome activation and fibrosis.

Funder

National Institutes of Health

Shanghai Pujiang Program

National Center for Advancing Translational Sciences of the National Institutes of Health

US Department of Veterans Affairs award

MVP

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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