{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:40:47Z","timestamp":1791038447504,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,1,13]],"date-time":"2010-01-13T00:00:00Z","timestamp":1263340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Familial hypercholesterolaemia (FH) is a human inherited disorder of metabolism characterised by increased serum low\u2010density lipoprotein (LDL) cholesterol. It is caused by defects in the LDL\u2010receptor pathway that impair normal uptake and clearance of LDL by the liver. The commonest cause of FH is mutations in <jats:italic>LDLR<\/jats:italic>, the gene for the LDL receptor, but defects also occur in <jats:italic>APOB<\/jats:italic> that encodes its major protein ligand. More recently, defects in two other genes, <jats:italic>LDLRAP1<\/jats:italic> and <jats:italic>PCSK9<\/jats:italic>, have been found in patients with FH and investigation of these has shed new light on the functioning and complexity of the LDL receptor pathway. Cells from patients with autosomal recessive hypercholesterolaemia (ARH) fail to internalise the LDL receptor because they carry two defective alleles of LDLRAP1, a gene that encodes a specific clathrin adaptor protein. PCSK9 encodes proprotein convertase subtilisin kexin type 9, a secreted protein that binds to the LDL receptor and promotes its degradation. Gain\u2010of function mutations in <jats:italic>PCSK9<\/jats:italic> are autosomal dominant and cause hypercholesterolaemia because they increase the affinity of PCSK9 protein for the LDL receptor, whereas loss\u2010of\u2010function mutations reduce serum cholesterol because LDL\u2010receptor protein is exposed to reduced PCSK9\u2010mediated degradation. Thus, PCSK9 has become a new target for cholesterol\u2010lowering drug therapy. \u00a9 2010 IUBMB IUBMB Life, 62(2): 125\u2013131, 2010<\/jats:p>","DOI":"10.1002\/iub.299","type":"journal-article","created":{"date-parts":[[2010,1,13]],"date-time":"2010-01-13T16:32:41Z","timestamp":1263400361000},"page":"125-131","source":"Crossref","is-referenced-by-count":20,"title":["Rare genetic causes of autosomal dominant or recessive hypercholesterolaemia"],"prefix":"10.1002","volume":"62","author":[{"given":"Anne K.","family":"Soutar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,1,13]]},"reference":[{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0836"},{"key":"e_1_2_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn422"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.a2423"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.14.7.1066"},{"key":"e_1_2_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2006.09.030"},{"key":"e_1_2_4_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_2_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)42605-7"},{"key":"e_1_2_4_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00219339"},{"key":"e_1_2_4_10_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.1999.550507.x"},{"key":"e_1_2_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2006.10.003"},{"key":"e_1_2_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2008.00436.x"},{"key":"e_1_2_4_13_2","doi-asserted-by":"publisher","DOI":"10.1258\/096914106778440617"},{"key":"e_1_2_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(64)90196-2"},{"key":"e_1_2_4_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6677"},{"key":"e_1_2_4_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/318795"},{"key":"e_1_2_4_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216445"},{"key":"e_1_2_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm232"},{"key":"e_1_2_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1161"},{"key":"e_1_2_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000190668.94752.ab"},{"key":"e_1_2_4_21_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300203-JLR200"},{"key":"e_1_2_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1534923100"},{"key":"e_1_2_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402133101"},{"key":"e_1_2_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501652102"},{"key":"e_1_2_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1509"},{"key":"e_1_2_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000134621.14315.43"},{"key":"e_1_2_4_27_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800091-JLR200"},{"key":"e_1_2_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1235"},{"key":"e_1_2_4_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C700095200"},{"key":"e_1_2_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20882"},{"key":"e_1_2_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi128"},{"key":"e_1_2_4_32_2","unstructured":"Herbert B. Patel D. Waddington S. Eden E. R. McALeenan A. Sun X.\u2010M. andSoutar A. K.Increased secretion of triglyceride\u2010rich lipoproteins by transgenic mice expressing human D374Y PCSK9 under physiological genetic control. Unpublished observation."},{"key":"e_1_2_4_33_2","doi-asserted-by":"publisher","DOI":"10.1086\/507488"},{"key":"e_1_2_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2006.08.039"},{"key":"e_1_2_4_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22911"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fiub.299","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T16:58:49Z","timestamp":1700585929000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,13]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,2]]}},"alternative-id":["10.1002\/iub.299"],"URL":"https:\/\/doi.org\/10.1002\/iub.299","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1,13]]}}}