ABSTRACT Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential

components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney

failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the

glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome

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customer support SIMILAR CONTENT BEING VIEWED BY OTHERS KIF21A DEFICIENCY LEADS TO IMPAIRED GLOMERULAR FILTRATION BARRIER FUNCTION Article Open access 06 November 2023 DISTINCT FUNCTIONAL

REQUIREMENTS FOR PODOCALYXIN IN IMMATURE AND MATURE PODOCYTES REVEAL MECHANISMS OF HUMAN KIDNEY DISEASE Article Open access 10 June 2020 PODOCYTE-SPECIFIC CRB2 KNOCKOUT MICE DEVELOP FOCAL

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  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the family members for their participation in these studies and M.A. Arnaout for discussions about the manuscript.

This work was supported by grants from the US National Institutes of Health (M.R.P., P.M. and R.K.) as well as the Howard Hughes Medical Institute (P.L.S. and D.E.C.). J.R. was supported by

the KMD Foundation and the KUFA-ASN Research Grant. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medicine, Renal Unit, Massachusetts General Hospital and Harvard Medical

School, Boston, 02129, Massachusetts, USA Jochen Reiser, Clemens C Möller, Mehmet M Altintas & Changli Wei * Renal Division, Department of Medicine, Brigham and Women's Hospital and

Harvard Medical School, Boston, 02115, Massachusetts, USA Krishna R Polu, Peter Kenlan, Stephanie Herbert & Martin R Pollak * Department of Medicine, Mount Sinai School of Medicine, New

York, 10029, New York, USA Christian Faul & Peter Mundel * Renal Unit, Instituto del Riñon-Fresenius Medical Care, Colombia Ivan Villegas * Department of Pathology, Instituto Nacional

de Cardiologia Ignacio Chavez, Mexico, 14080, D.F., Mexico Carmen Avila-Casado * Program in Membrane Biology and Renal Unit, Massachusetts General Hospital and Harvard Medical School,

Boston, 02129, Massachusetts, USA Mary McGee & Dennis Brown * Department of Medicine, Center for Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston,

02115, Massachusetts, USA Hikaru Sugimoto & Raghu Kalluri * Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital, Boston, 02115, Massachusetts, USA Paula L

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Scholar CORRESPONDING AUTHORS Correspondence to Jochen Reiser or Martin R Pollak. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY

INFORMATION SUPPLEMENTARY FIG. 1 Summary of TRPC6 mutations. (PDF 99 kb) SUPPLEMENTARY TABLE 1 Primer sequences. (PDF 43 kb) SUPPLEMENTARY NOTE Clinical information. (PDF 40 kb) RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Reiser, J., Polu, K., Möller, C. _et al._ TRPC6 is a glomerular slit diaphragm-associated channel required for

normal renal function. _Nat Genet_ 37, 739–744 (2005). https://doi.org/10.1038/ng1592 Download citation * Received: 12 April 2005 * Accepted: 23 May 2005 * Published: 27 May 2005 * Issue

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