{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:24:56Z","timestamp":1792092296426,"version":"4.4.0"},"reference-count":25,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5729","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2005,6,17]]},"abstract":"<jats:p>\n                    Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the\n                    <jats:italic>TRPC6<\/jats:italic>\n                    gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.\n                  <\/jats:p>","DOI":"10.1126\/science.1106215","type":"journal-article","created":{"date-parts":[[2005,5,6]],"date-time":"2005-05-06T20:39:24Z","timestamp":1115411964000},"page":"1801-1804","source":"Crossref","is-referenced-by-count":968,"title":["A Mutation in the\n                    <i>TRPC6<\/i>\n                    Cation Channel Causes Familial Focal Segmental Glomerulosclerosis"],"prefix":"10.1126","volume":"308","author":[{"given":"Michelle P.","family":"Winn","sequence":"first","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Conlon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin L.","family":"Lynn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merry Kay","family":"Farrington","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Creazzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April F.","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu Ying","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Ebersviller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Burchette","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Pericak-Vance","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Howell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery M.","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA."},{"name":"Department of Nephrology, Beaumont Hospital, Dublin, Ireland."},{"name":"Department of Nephrology, Christchurch Hospital, Christchurch, New Zealand. 5Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004670050555"},{"key":"e_1_3_1_3_2","first-page":"325","volume":"53","year":"2000","unstructured":"A. Hurtado et al., Clin. Nephrol.53, 325 (2000).","journal-title":"Clin. Nephrol."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(96)90098-0"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80057-X"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/74166"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/73456"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00384.x"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5828"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00527-2"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7458"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00727.x"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00338.2003"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000039661.06947.FD"},{"key":"e_1_3_1_15_2","unstructured":"The HEK 293 cell line was originally derived from human embryonic kidney tissue and its morphological features bear little or no resemblance to those of mature renal cell lineages. Thus the absence of TRPC6 expression in HEK cells probably has little bearing on whether the protein is actually expressed in mature kidney tissue. Examples of this phenomenon are the angiotensin receptors which are not expressed in HEK cells but are expressed throughout the kidney."},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/16711"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00031.x"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.3109\/07435809809032613"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.07.010"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1150"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.7962"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64357-X"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17988"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112849"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00438-5"},{"key":"e_1_3_1_26_2","unstructured":"We thank the members of the family described here the Center for Human Genetics core facilities for assistance J. Burch for technical assistance and R. S. Williams for helpful discussions. Supported in part by grants from NIH."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1106215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:32:58Z","timestamp":1704843178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1106215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,17]]},"references-count":25,"journal-issue":{"issue":"5729","published-print":{"date-parts":[[2005,6,17]]}},"alternative-id":["10.1126\/science.1106215"],"URL":"https:\/\/doi.org\/10.1126\/science.1106215","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1009827.325219","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1009827.325412","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,17]]}}}