{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:05:16Z","timestamp":1792199116381,"version":"4.4.0"},"reference-count":175,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>FAM20C is a gene coding for a protein kinase that targets S-X-E\/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.<\/jats:p>","DOI":"10.3390\/ijms22158039","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T22:35:02Z","timestamp":1627425302000},"page":"8039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes"],"prefix":"10.3390","volume":"22","author":[{"given":"Icela","family":"Palma-Lara","sequence":"first","affiliation":[{"name":"Laboratorio de Morfolog\u00eda Celular y Molecular, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Instituto Polit\u00e9cnico Nacional, Escuela Superior de Medicina, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-6586","authenticated-orcid":false,"given":"Monserrat","family":"P\u00e9rez-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratorio de Morfolog\u00eda Celular y Molecular, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Instituto Polit\u00e9cnico Nacional, Escuela Superior de Medicina, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Garc\u00eda Alonso-Themann","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Perinatolog\u00eda, Seguimiento Pedi\u00e1trico, Ciudad de M\u00e9xico 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3255-4051","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"Espinosa-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Cl\u00ednica, Hospital General de M\u00e9xico, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Godinez-Aguilar","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Investigaci\u00f3n, Hospital Ju\u00e1rez de M\u00e9xico, Ciudad de M\u00e9xico 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9690-1940","authenticated-orcid":false,"given":"Jos\u00e9","family":"Bonilla-Delgado","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Investigaci\u00f3n, Hospital Ju\u00e1rez de M\u00e9xico, Ciudad de M\u00e9xico 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"L\u00f3pez-Ornelas","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Investigaci\u00f3n, Hospital Ju\u00e1rez de M\u00e9xico, Ciudad de M\u00e9xico 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Victoria-Acosta","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Investigaci\u00f3n, Hospital Ju\u00e1rez de M\u00e9xico, Ciudad de M\u00e9xico 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-066X","authenticated-orcid":false,"given":"Mar\u00eda Guadalupe","family":"Olgu\u00edn-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro Dermatol\u00f3gico \u201cDr. Ladislao de la Pascua\u201d SSPCDMX, Departamento de Educaci\u00f3n e Investigaci\u00f3n, Ciudad de M\u00e9xico 06780, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-6087","authenticated-orcid":false,"given":"Jos\u00e9","family":"Moreno","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Investigaci\u00f3n, Hospital Ju\u00e1rez de M\u00e9xico, Ciudad de M\u00e9xico 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8392-859X","authenticated-orcid":false,"given":"Carmen","family":"Palacios-Reyes","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Investigaci\u00f3n, Hospital Ju\u00e1rez de M\u00e9xico, Ciudad de M\u00e9xico 07760, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1086\/522240","article-title":"Mutations in FAM20C Are Associated with Lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), Highlighting a Crucial Molecule in Bone Development","volume":"81","author":"Simpson","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.2044-8260.1989.tb00809.x","article-title":"Factors of schizoid personality","volume":"28","author":"Raine","year":"1989","journal-title":"Br. J. Clin. Psychol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.ejmg.2014.07.001","article-title":"Raine syndrome: An overview","volume":"57","author":"Faundes","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/ajmg.a.38598","article-title":"Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non-lethal form of Raine syndrome","volume":"176","author":"Tamai","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00198-018-4667-6","article-title":"A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee","volume":"30","author":"Rolvien","year":"2019","journal-title":"Osteoporos. Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sheth, J., Bhavsar, R., Gandhi, A., Sheth, F., and Pancholi, D. (2018). A case of Raine syndrome presenting with facial dysmorphy and review of literature. BMC Med. Genet., 19.","DOI":"10.1186\/s12881-018-0593-x"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/BF01957934","article-title":"Osteopetrosis: Brain ultrasound and computed tomography findings","volume":"151","author":"Patel","year":"1992","journal-title":"Eur. J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00401-001-0469-5","article-title":"Neuropathology of Raine syndrome","volume":"103","author":"Rickert","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1002\/ajmg.a.32022","article-title":"Raine syndrome: A rare lethal osteosclerotic bone dysplasia. Prenatal diagnosis, autopsy, and neuropathological findings","volume":"143","author":"Chitayat","year":"2007","journal-title":"Am. J. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1177\/8756479311409938","article-title":"Raine syndrome","volume":"27","author":"Michael","year":"2011","journal-title":"J. Diagn. Med. Sonogr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00247-010-1875-4","article-title":"Raine syndrome: Expanding the radiological spectrum","volume":"41","author":"Koob","year":"2011","journal-title":"Pediatr. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ishikawa, H.O., Xu, A., Ogura, E., Manning, G., and Irvine, K.D. (2012). The raine syndrome protein FAM20C is a golgi kinase that phosphorylates bio-mineralization proteins. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042988"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.cell.2015.05.028","article-title":"A Single Kinase Generates the Majority of the Secreted Phosphoproteome","volume":"161","author":"Tagliabracci","year":"2015","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1096\/fj.15-273607","article-title":"Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone","volume":"30","author":"Yang","year":"2016","journal-title":"FASEB J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.bbapap.2015.03.015","article-title":"The secretory pathway kinases","volume":"1854","author":"Sreelatha","year":"2015","journal-title":"Biochim. Biophys. Acta. Proteins Proteom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14085","DOI":"10.3390\/ijms140714085","article-title":"Presence of proNGF-Sortilin Signaling Complex in Nigral Dopamine Neurons and Its Variation in Relation to Aging, Lactacystin and 6-OHDA Insults","volume":"14","author":"Xia","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1002\/jcp.26200","article-title":"FAM20C regulates osteoblast behaviors and intracellular signaling pathways in a cell-autonomous manner","volume":"233","author":"Liu","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nalbant, D., Youn, H., Nalbant, S.I., Sharma, S., Cobos, E., Beale, E.G., Du, Y., and Williams, S.C. (2005). FAM20: An evolutionarily conserved family of secreted proteins expressed in hematopoietic cells. BMC Genom., 6.","DOI":"10.1186\/1471-2164-6-11"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ajmg.a.36187","article-title":"Enamel-renal-gingival syndrome and FAM20A mutations","volume":"164","author":"Kantaputra","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1042\/BJ20090474","article-title":"FAM20B is a kinase that phosphorylates xylose in the glycosaminoglycan-protein linkage region","volume":"421","author":"Koike","year":"2009","journal-title":"Biochem. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15723","DOI":"10.1073\/pnas.1417993111","article-title":"Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis","volume":"111","author":"Wen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1111\/febs.14984","article-title":"Bone and connective tissue disorders caused by defects in glycosaminoglycan biosynthesis: A panoramic view","volume":"286","author":"Paganini","year":"2019","journal-title":"FEBS J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/cge.13530","article-title":"A novel gene (FAM20B encoding glycosaminoglycan xylosylkinase) for neonatal short limb dysplasia resembling Desbuquois dysplasia","volume":"95","author":"Kuroda","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10574","DOI":"10.1073\/pnas.1309211110","article-title":"Crystal structure of the Golgi casein kinase","volume":"110","author":"Xiao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1126\/science.1217817","article-title":"Secreted kinase phosphorylates extracellular proteins that regulate biomineralization","volume":"336","author":"Tagliabracci","year":"2012","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1517\/14728222.2016.1091883","article-title":"Casein kinases as potential therapeutic targets","volume":"20","author":"Cozza","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.tibs.2012.11.008","article-title":"Secreted protein kinases","volume":"38","author":"Tagliabracci","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.1038\/s41598-017-03960-x","article-title":"Specific ablation of mouse Fam20C in cells expressing type i collagen leads to skeletal defects and hypophosphatemia","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.2174\/1871527313666141023151642","article-title":"The Implications of Sortilin\/Vps10p Domain Receptors in Neurological and Human Diseases","volume":"13","author":"Wilson","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0169-6009(08)80225-5","article-title":"Osteopontin-hydroxyapatite interactions in vitro: Inhibition of hydroxyapatite formation and growth in a gelatin-gel","volume":"22","author":"Boskey","year":"1993","journal-title":"Bone Miner."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/s41598-018-19253-w","article-title":"Biomolecular Regulation, Composition and Nanoarchitecture of Bone Mineral","volume":"8","author":"Poundarik","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00223-004-1288-1","article-title":"Importance of phosphorylation for osteopontin regulation of biomineralization","volume":"77","author":"Gericke","year":"2005","journal-title":"Calcif. Tissue Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1210\/en.2007-1205","article-title":"Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-Peptide(s) are directly responsible for defective mineralization in HYP","volume":"149","author":"Martin","year":"2008","journal-title":"Endocrinology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1042\/BJ20140702","article-title":"Osteopontin mediates mineralization and not osteogenic cell development in vitro","volume":"464","author":"Holm","year":"2014","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.clinbiochem.2018.07.003","article-title":"The multiple functions and mechanisms of osteopontin","volume":"59","author":"Icer","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1359\/jbmr.1998.13.7.1101","article-title":"Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro","volume":"13","author":"Rittling","year":"1998","journal-title":"J. Bone Miner. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1096\/fj.201900880R","article-title":"Fam20C-mediated phosphorylation of osteopontin is critical for its secretion but dispensable for its action as a cytokine in the activation of hepatic stellate cells in liver fibrogenesis","volume":"34","author":"Tibaldi","year":"2020","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1210\/en.2002-220996","article-title":"Osteopontin Deficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation","volume":"144","author":"Kitahara","year":"2003","journal-title":"Endocrinology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1177\/0022034510363250","article-title":"Different forms of DMP1 play distinct roles in mineralization","volume":"89","author":"Gericke","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.archoralbio.2012.03.005","article-title":"Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues","volume":"57","author":"Suzuki","year":"2012","journal-title":"Arch. Oral Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"34700","DOI":"10.1074\/jbc.M305315200","article-title":"Evidence for the proteolytic processing of dentin matrix protein 1: Identification and characterization of processed fragments and cleavage sites","volume":"278","author":"Qin","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/ng1905","article-title":"Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism","volume":"38","author":"Feng","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/jbmr.226","article-title":"The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa c-terminal fragment","volume":"26","author":"Lu","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bone.2008.10.040","article-title":"Molecular analysis of DMP1 mutants causing autosomal recessive hypophosphatemic rickets","volume":"44","author":"Farrow","year":"2009","journal-title":"Bone"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.1074\/jbc.M412911200","article-title":"Dmp1-deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype","volume":"280","author":"Ye","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3109\/03008207.2014.923414","article-title":"Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice","volume":"55","author":"Wang","year":"2014","journal-title":"Connect. Tissue Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1002\/jcb.25742","article-title":"Extracellular Phosphate Induces the Expression of Dentin Matrix Protein 1 Through the FGF Receptor in Osteoblasts","volume":"118","author":"Nishino","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00418-016-1490-z","article-title":"Immunohistochemical analysis of dentin matrix protein 1 (Dmp1) phosphorylation by Fam20C in bone: Implications for the induction of biomineralization","volume":"147","author":"Oya","year":"2017","journal-title":"Histochem. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e98699","DOI":"10.15252\/embj.201798699","article-title":"Secretory kinase Fam20C tunes endoplasmic reticulum redox state via phosphorylation of Ero1\u03b1","volume":"37","author":"Zhang","year":"2018","journal-title":"EMBO J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1210\/en.2009-0216","article-title":"Matrix extracellular phosphoglycoprotein (MEPE) is a new bone renal hormone and vascularization modulator","volume":"150","author":"David","year":"2009","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00418-004-0653-5","article-title":"Mepe is expressed during skeletal development and regeneration","volume":"121","author":"Lu","year":"2004","journal-title":"Histochem. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1359\/jbmr.070709","article-title":"Regulation of osteoclast differentiation and function by phosphate: Potential role of osteoclasts in the skeletal abnormalities in hypophosphatemic conditions","volume":"22","author":"Hayashibara","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1681\/ASN.2008030315","article-title":"Matrix extracellular phosphoglycoprotein inhibits phosphate transport","volume":"19","author":"Marks","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1074\/jbc.M203250200","article-title":"Targeted disruption of the osteoblast\/osteocyte factor 45 gene (Of45) results in increased bone formation and bone mass","volume":"278","author":"Gowen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/labinvest.2008.114","article-title":"Recent advances in the renal-skeletal-gut axis that controls phosphate homeostasis","volume":"89","author":"Kiela","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e10378","DOI":"10.1002\/jbm4.10378","article-title":"FAM20C-Mediated Phosphorylation of MEPE and Its Acidic Serine- and Aspartate-Rich Motif","volume":"4","author":"Christensen","year":"2020","journal-title":"JBMR Plus"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0006-291X(02)02125-3","article-title":"Inhibition of MEPE cleavage by Phex","volume":"297","author":"Guo","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1152\/ajprenal.00304.2010","article-title":"Asarm peptides: PHEX-dependent and -independent regulation of serum phosphate","volume":"300","author":"David","year":"2011","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1677\/joe.1.07059","article-title":"Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity","volume":"192","author":"Liu","year":"2007","journal-title":"J. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1177\/154411130401500503","article-title":"Fgf23, Mepe and Phex","volume":"15","author":"Rowe","year":"2004","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1359\/jbmr.090832","article-title":"Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage","volume":"25","author":"Addison","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bone.2004.09.015","article-title":"Surface plasmon resonance (SPR) confirms that MEPE binds to PHEX via the MEPE-ASARM motif: A model for impaired mineralization in X-linked rickets (HYP)","volume":"36","author":"Rowe","year":"2005","journal-title":"Bone"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1369\/0022155416635569","article-title":"MEPE Localization in the Craniofacial Complex and Function in Tooth Dentin Formation","volume":"64","author":"Gullard","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.bone.2015.05.030","article-title":"Age dependent regulation of bone-mass and renal function by the MEPE ASARM-MOTIF","volume":"79","author":"Zelenchuk","year":"2015","journal-title":"Bone"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.bbrc.2010.06.085","article-title":"Differentiation of odontoblasts is negatively regulated by MEPE via its C-terminal fragment","volume":"398","author":"Wang","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/s41436-018-0300-5","article-title":"Variants affecting diverse domains of MEPE are associated with two distinct bone disorders, a craniofacial bone defect and otosclerosis","volume":"21","author":"Schrauwen","year":"2019","journal-title":"Genet. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"18370","DOI":"10.1074\/jbc.M602469200","article-title":"Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis: Secretion of fibroblast growth factor 23 requires O-glycosylation","volume":"281","author":"Kato","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Xiao, Z., Huang, J., Cao, L., Liang, Y., Han, X., and Quarles, L.D. (2014). Osteocyte-specific deletion of Fgfr1 suppresses FGF23. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104154"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jmgm.2012.10.007","article-title":"A structural and functional model for human bone sialoprotein","volume":"39","author":"Vincent","year":"2013","journal-title":"J. Mol. Graph. Model."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1359\/jbmr.1997.12.8.1210","article-title":"Characterization of native and recombinant bone sialoprotein: Delineation of the mineral-binding and cell adhesion domains and structural analysis of the RGD domain","volume":"12","author":"Stubbs","year":"1997","journal-title":"J. Bone Miner. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1042\/BJ20091864","article-title":"Phosphorylation of Ser136 is critical for potent bone sialoprotein-mediated nucleation of hydroxyapatite crystals","volume":"428","author":"Baht","year":"2010","journal-title":"Biochem. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.bone.2007.04.191","article-title":"Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization In Vitro","volume":"41","author":"Gordon","year":"2007","journal-title":"Bone"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1002\/ajmg.a.61366","article-title":"Nosology and classification of genetic skeletal disorders: 2019 revision","volume":"179","author":"Mortier","year":"2019","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bouet, G., Bouleftour, W., Juignet, L., Linossier, M.-T., Thomas, M., Vanden-Bossche, A., Aubin, J.E., Vico, L., Marchat, D., and Malaval, L. (2015). The Impairment of Osteogenesis in Bone Sialoprotein (BSP) Knockout Calvaria Cell Cultures Is Cell Density Dependent. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117402"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Bouleftour, W., Boudiffa, M., Wade-Gueye, N.M., Bou\u00ebt, G., Cardelli, M., Laroche, N., Vanden-Bossche, A., Thomas, M., Bonnelye, E., and Aubin, J.E. (2014). Skeletal development of mice lacking Bone Sialoprotein (BSP)\u2014Impairment of long bone growth and progressive establishment of high trabecular bone mass. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095144"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1084\/jem.20071294","article-title":"Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis","volume":"205","author":"Malaval","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/0022034512469026","article-title":"Deficiency in acellular cementum and periodontal attachment in Bsp null mice","volume":"92","author":"Foster","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.bone.2009.09.007","article-title":"Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing","volume":"46","author":"Monfoulet","year":"2010","journal-title":"Bone"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.bone.2009.06.005","article-title":"Absence of bone sialoprotein (BSP) impairs cortical defect repair in mouse long bone","volume":"45","author":"Malaval","year":"2009","journal-title":"Bone"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.1073\/pnas.1402218111","article-title":"Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis","volume":"111","author":"Tagliabracci","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23","volume":"26","author":"White","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/jbmr.3195","article-title":"Klotho Lacks an FGF23-Independent Role in Mineral Homeostasis","volume":"32","author":"Andrukhova","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bone.2014.06.026","article-title":"Hypophosphatemic osteomalacia and bone sclerosis caused by a novel homozygous mutation of the FAM20C gene in an elderly man with a mild variant of raine syndrome","volume":"67","author":"Takeyari","year":"2014","journal-title":"Bone"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1073\/pnas.0712361105","article-title":"A translocation causing increased \u03b1-Klotho level results in hypophosphatemic rickets and hyperparathyroidism","volume":"105","author":"Brownstein","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","first-page":"4003","article-title":"The parathyroid is a target organ for FGF23 in rats","volume":"117","author":"Galitzer","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e125007","DOI":"10.1172\/jci.insight.125007","article-title":"A G protein-coupled, IP3\/protein kinase C pathway controlling the synthesis of phosphaturic hormone FGF23","volume":"4","author":"He","year":"2019","journal-title":"JCI Insight."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1210\/en.2016-1451","article-title":"C-terminal but not intact fibroblast growth factor 23 levels","volume":"158","author":"Knab","year":"2017","journal-title":"Endocrinology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.bbrc.2003.12.102","article-title":"FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa","volume":"314","author":"Shimada","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1210\/en.2003-1768","article-title":"Transgenic mice expressing fibroblast growth factor 23 under the control of the \u03b11(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis","volume":"145","author":"Larsson","year":"2004","journal-title":"Endocrinology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9843","DOI":"10.1074\/jbc.M210490200","article-title":"The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency","volume":"278","author":"Bai","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.1210\/en.2004-0233","article-title":"Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders","volume":"145","author":"Bai","year":"2004","journal-title":"Endocrinology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1210\/jcem.82.2.3765","article-title":"Autosomal dominant hypophosphatemic rickets\/osteomalacia: Clinical characterization of a novel renal phosphate-wasting disorder","volume":"82","author":"Econs","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Lysaght, A.C., Yuan, Q., Fan, Y., Kalwani, N., Caruso, P., Cunnane, M.B., Lanske, B., and Stankovic, K.M. (2014). FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107681"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1096\/fj.10-177816","article-title":"Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling","volume":"25","author":"Martin","year":"2011","journal-title":"FASEB J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/jbmr.2079","article-title":"Increased osteopontin contributes to inhibition of bone mineralization in FGF23-deficient mice","volume":"29","author":"Yuan","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1210\/en.2016-1642","article-title":"A mutation in the Dmp1 gene alters phosphate responsiveness in mice","volume":"158","author":"Ichikawa","year":"2017","journal-title":"Endocrinology"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Wang, X., Wang, S., Li, C., Gao, T., Liu, Y., Rangiani, A., Sun, Y., Hao, J., George, A., and Lu, Y. (2012). Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002708"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1074\/jbc.C500457200","article-title":"Regulation of fibroblast growth factor-23 signaling by Klotho","volume":"281","author":"Kurosu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1039\/C6MB00111D","article-title":"Systematic network-based discovery of a Fam20C inhibitor (FL-1607) with apoptosis modulation in triple-negative breast cancer","volume":"12","author":"Qin","year":"2016","journal-title":"Mol. Biosyst."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Yalak, G., Shiu, J.Y., Schoen, I., Mitsi, M., and Vogel, V. (2019). Phosphorylated fibronectin enhances cell attachment and upregulates mechanical cell functions. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218893"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1177\/0300985812453177","article-title":"Amelogenesis imperfecta and other biomineralization defects in Fam20a and Fam20c null mice","volume":"49","author":"Vogel","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e103841","DOI":"10.15252\/embj.2019103841","article-title":"Phosphorylation switches protein disulfide isomerase activity to maintain proteostasis and attenuate ER stress","volume":"39","author":"Yu","year":"2020","journal-title":"EMBO J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/jth.14426","article-title":"In vitro phosphorylation of von Willebrand factor by FAM20c enhances its ability to support platelet adhesion","volume":"17","author":"Da","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1161\/ATVBAHA.119.313247","article-title":"Ser-phosphorylation of PCSK9 (Proprotein Convertase Subtilisin-Kexin 9) by Fam20C (Family with Sequence Similarity 20, Member C) kinase enhances its ability to degrade the LDLR (Low-Density Lipoprotein Receptor)","volume":"39","author":"Gauthier","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1111\/febs.15212","article-title":"Proprotein convertase 7 (PCSK7) reduces apoA-V levels","volume":"287","author":"Ashraf","year":"2020","journal-title":"FEBS J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1172\/JCI80851","article-title":"Sortilin mediates vascular calcification via its recruitment into extracellular vesicles","volume":"126","author":"Goettsch","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"9098","DOI":"10.1073\/pnas.1706441114","article-title":"Phosphorylation of serine96 of histidine-rich calcium-binding protein by the Fam20C kinase functions to prevent cardiac arrhythmia","volume":"114","author":"Pollak","year":"2017","journal-title":"Proc. Natl. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12014-018-9205-1","article-title":"Phosphotyrosine profiling of human cerebrospinal fluid","volume":"15","author":"Sathe","year":"2018","journal-title":"Clin. Proteom."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1021\/pr100058r","article-title":"Motif analysis of phosphosites discloses a potential prominent role of the golgi casein kinase (GCK) in the generation of human plasma phospho-proteome","volume":"9","author":"Salvi","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s13361-018-1915-0","article-title":"Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles","volume":"29","author":"Lietz","year":"2018","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"11436","DOI":"10.1038\/ncomms11436","article-title":"Analytic framework for peptidomics applied to large-scale neuropeptide identification","volume":"7","author":"Secher","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fnana.2019.00031","article-title":"Regional and cellular mapping of sortilin immunoreactivity in adult human brain","volume":"13","author":"Xu","year":"2019","journal-title":"Front. Neuroanat."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"rs3","DOI":"10.1126\/scisignal.2001570","article-title":"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation","volume":"4","author":"Rigbolt","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.bone.2012.02.014","article-title":"Absence of bone sialoprotein (BSP) impairs primary bone formation and resorption: The marrow ablation model under PTH challenge","volume":"50","author":"Boudiffa","year":"2012","journal-title":"Bone"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1007\/s002470050473","article-title":"Intracranial calcification in Raine syndrome: Radiological pathological correlation","volume":"28","author":"McDonald","year":"1998","journal-title":"Pediatr. Radiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1084\/jem.20020911","article-title":"Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: Evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo","volume":"196","author":"Speer","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nrc2345","article-title":"Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): Multifunctional proteins in cancer","volume":"8","author":"Castronovo","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2001271","DOI":"10.1002\/adhm.202001271","article-title":"Multiple Pathways for Pathological Calcification in the Human Body","volume":"10","author":"Vidavsky","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nrn2516","article-title":"VPS10P-domain receptors\u2014Regulators of neuronal viability and function","volume":"9","author":"Willnow","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"12602","DOI":"10.1074\/jbc.M110.170217","article-title":"BACE1 retrograde trafficking is uniquely regulated by the cytoplasmic domain of sortilin","volume":"286","author":"Finan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fnana.2017.00045","article-title":"Sortilin fragments deposit at senile plaques in human cerebrum","volume":"11","author":"Hu","year":"2017","journal-title":"Front. Neuroanat."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1242\/jcs.183541","article-title":"Sortilin regulates sorting and secretion of Sonic hedgehog","volume":"129","author":"Campbell","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_123","first-page":"335.2","article-title":"FAM20C is Essential for Maintaining Brain Homeostasis","volume":"33","author":"Zhang","year":"2019","journal-title":"FASEB J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1093\/eurheartj\/ehn328","article-title":"The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy","volume":"29","author":"Arvanitis","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Amioka, M.I., Nakano, Y.I., Ochi, H., Onohara, Y., Sairaku, A., Tokuyama, T., Motoda, C., Matsumura, H., Tomomori, S., and Hironobe, N. (2019). Ser96Ala genetic variant of the human histidine-rich calcium-binding protein is a genetic predictor of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213208"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1161\/01.RES.77.4.735","article-title":"An isolated cardiac conduction disease maps to chromosome 19q","volume":"77","author":"Stephan","year":"1995","journal-title":"Circ. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1161\/01.CIR.91.6.1633","article-title":"Gene for progressive familial heart block type I maps to chromosome 19q13","volume":"91","author":"Brink","year":"1995","journal-title":"Circulation"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1161\/ATVBAHA.113.301743","article-title":"Profiling of atherosclerotic lesions by gene and tissue microarrays reveals pcsk6 as a novel protease in unstable carotid atherosclerosis","volume":"33","author":"Perisic","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"36610","DOI":"10.1074\/jbc.M113.453183","article-title":"Proprotein Convertase Subtilisin\/Kexin Type 7 (PCSK7) Is Essential for the Zebrafish Development and Bioavailability of Transforming Growth Factor \u03b21a (TGF\u03b21a)","volume":"288","author":"Turpeinen","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ajhg.2014.01.009","article-title":"Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks","volume":"94","author":"Peloso","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrd3699","article-title":"The biology and therapeutic targeting of the proprotein convertases","volume":"11","author":"Seidah","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/ng1161","article-title":"Mutations in PCSK9 cause autosomal dominant hypercholesterolemia","volume":"34","author":"Abifadel","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1056\/NEJMoa054013","article-title":"Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease","volume":"354","author":"Cohen","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_134","first-page":"2103","article-title":"Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice","volume":"43","author":"Miao","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/jbmr.3034","article-title":"Raine Syndrome (OMIM #259775), Caused By FAM20C Mutation, Is Congenital Sclerosing Osteomalacia with Cerebral Calcification (OMIM 259660)","volume":"32","author":"Whyte","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1399-0004.2008.01118.x","article-title":"Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia","volume":"75","author":"Simpson","year":"2009","journal-title":"Clin. Genet."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1002\/ajmg.a.36160","article-title":"Hereditary deletion of the entire FAM20C gene in a patient with Raine syndrome","volume":"161","author":"Ababneh","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/pd.5818","article-title":"Raine syndrome: Prenatal diagnosis based on recognizable fetal facial features and characteristic intracranial calcification","volume":"40","author":"Aboulghar","year":"2020","journal-title":"Prenat. Diagn."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Zavala, A., Cort\u00e9s-Camacho, F., Palma-Lara, I., God\u00ednez-Aguilar, R., Espinosa, A.M., P\u00e9rez-Dur\u00e1n, J., Villanueva-Ocampo, P., Ugarte-Briones, C., Serrano-Bello, C.A., and S\u00e1nchez-Santiago, P.J. (2020). Two novel FAM20C variants in a family with raine syndrome. Genes, 11.","DOI":"10.3390\/genes11020222"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13023-020-01373-0","article-title":"Natural history of non-lethal Raine syndrome during childhood","volume":"15","author":"Mameli","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Acevedo, A.C., Poulter, J.A., Alves, P.G., de Lima, C.L., Castro, L.C., Yamaguti, P.M., Paula, L.M., Parry, D.A., Logan, C.V., and Smith, C.E.L. (2015). Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations. BMC Med. Genet., 16.","DOI":"10.1186\/s12881-015-0154-5"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.ejmg.2016.09.018","article-title":"Non lethal Raine syndrome and differential diagnosis","volume":"59","author":"Elalaoui","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1002\/jbmr.1850","article-title":"Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification","volume":"28","author":"Rafaelsen","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1399-0004.2010.01516.x","article-title":"Osteosclerotic bone dysplasia in siblings with a Fam20C mutation","volume":"80","author":"Fradin","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/gim.2017.173","article-title":"Genomic study of severe fetal anomalies and discovery of GREB1L mutations in renal agenesis","volume":"20","author":"Boissel","year":"2018","journal-title":"Genet. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1002\/ajmg.a.61291","article-title":"A novel FAM20C mutation causes a rare form of neonatal lethal Raine syndrome","volume":"179","author":"Hung","year":"2019","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00223-019-00599-w","article-title":"Non-lethal Raine Syndrome in a Middle-Aged Woman Caused by a Novel FAM20C Mutation","volume":"105","author":"Mamedova","year":"2019","journal-title":"Calcif. Tissue Int."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.13070\/rs.en.1.890","article-title":"Raine syndrome: A review and a report of metabolic bone disease as a new link","volume":"1","author":"Mahmood","year":"2014","journal-title":"Research"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1002\/ajmg.a.37159","article-title":"Report of a case of Raine syndrome and literature review","volume":"167","author":"Seidahmed","year":"2015","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000513384","article-title":"Nonlethal Raine Syndrome in a Newborn Boy Caused by a Novel FAM20C Variant","volume":"12","author":"Eras","year":"2021","journal-title":"Mol. Syndromol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s00223-020-00694-3","article-title":"A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age","volume":"107","author":"Eltan","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/MCD.0b013e32833a22c5","article-title":"Raine syndrome: A clinical, radiographic and genetic investigation of a case from the Indian subcontinent","volume":"19","author":"Kochar","year":"2010","journal-title":"Clin. Dysmorphol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jum.15426","article-title":"Raine Syndrome, a Rare Lethal Osteosclerotic Bone Dysplasia: Prenatal Diagnosis with 3-Dimensional Ultrasound and a Postnatal Clinical Exome Evaluation","volume":"40","author":"Lulla","year":"2021","journal-title":"J. Ultrasound Med."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Bajaj, S., Nabi, F., Shah, J., and Sheth, H. (2021). Recurrent variant c.1680C>A in FAM20C gene and genotype-phenotype correlation in a patient with Raine syndrome: A case report. BMC Pediatr., 21.","DOI":"10.1186\/s12887-021-02582-7"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1083\/jcb.201906047","article-title":"Protein quality control in the secretory pathway","volume":"218","author":"Sun","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1136\/jmg.26.12.786","article-title":"Unknown syndrome: Microcephaly, hypoplastic nose, exophthalmos, gum hyperplasia, cleft palate, low set ears, and osteosclerosis","volume":"26","author":"Raine","year":"1989","journal-title":"J. Med. Genet."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF00193823","article-title":"A new lethal sclerosing bone dysplasia","volume":"20","author":"Kingston","year":"1991","journal-title":"Skeletal Radiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/ajmg.1320430522","article-title":"New distinct lethal osteosclerotic bone dysplasia (Raine syndrome)","volume":"43","author":"Kan","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF01403707","article-title":"Intracranial calcification in Raine syndrome","volume":"26","author":"Coates","year":"1996","journal-title":"Pediatr. Radiol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/(SICI)1096-8628(19980724)78:4<382::AID-AJMG17>3.0.CO;2-E","article-title":"Raine syndrome","volume":"78","author":"Rejjal","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/(SICI)1096-8628(19990917)86:3<274::AID-AJMG15>3.0.CO;2-R","article-title":"Osteosclerosis, hypoplastic nose, and proptosis (Raine syndrome): Further delineation","volume":"86","author":"Shalev","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00019605-200009020-00004","article-title":"Raine dysplasia: A Brazilian case with a mild radiological involvement","volume":"9","author":"Acosta","year":"2000","journal-title":"Clin. Dysmorphol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/00019605-200107000-00015","article-title":"Raine syndrome: Report of a case with hand and foot anomalies","volume":"10","author":"Mahafza","year":"2001","journal-title":"Clin. Dysmorphol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/01.mcd.0000080413.95344.60","article-title":"Raine syndrome: Report of a family with three affected sibs and further delineation of the syndrome","volume":"12","author":"Wieczorek","year":"2003","journal-title":"Clin. Dysmorphol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00019605-200304000-00003","article-title":"Further delineation of Raine syndrome","volume":"12","author":"Jehier","year":"2003","journal-title":"Clin. Dysmorphol."},{"key":"ref_166","first-page":"723","article-title":"Raine Syndrome","volume":"89","author":"Gaigi","year":"2011","journal-title":"Tunis Med."},{"key":"ref_167","unstructured":"Abu, A.J., Bystricka, A., Qadir, M., and Nikolay, M.K.J. (2014). Raine Syndrome: Clinical and Radiological Features of a Case from the United Arab Emirates, Swiss Society of Neonatology."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bone.2014.10.007","article-title":"Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization","volume":"71","author":"Holm","year":"2015","journal-title":"Bone"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jsb.2010.11.013","article-title":"Possible role of DMP1 in dentin mineralization","volume":"174","author":"Beniash","year":"2011","journal-title":"J. Struct. Biol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1177\/0022034513504588","article-title":"The specific role of FAM20C in amelogenesis","volume":"92","author":"Wang","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4103\/0971-6866.132761","article-title":"Raine syndrome","volume":"20","author":"Vishwanath","year":"2014","journal-title":"Indian J. Hum. Genet."},{"key":"ref_172","first-page":"3304","article-title":"Raine Syndrome: A rare case presentation","volume":"4","author":"Das","year":"2017","journal-title":"Int. J. Med. Sci. Clin. Invent."},{"key":"ref_173","first-page":"89","article-title":"Raine syndrome associated with cytomegalovirus infection","volume":"47","year":"2005","journal-title":"Turk. J. Pediatr."},{"key":"ref_174","first-page":"6637180","article-title":"Hypophosphataemic Rickets Secondary to Raine Syndrome: A Review of the Literature and Case Reports of Three Paediatric Patients\u2019 Dental Management","volume":"2021","author":"Hirst","year":"2021","journal-title":"Case Rep. Pediatr."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1177\/154405910708601202","article-title":"Dentin Matrix Protein 1 (DMP1): New and important roles for biomineralization and phosphate homeostasis","volume":"86","author":"Qin","year":"2007","journal-title":"J. Dent. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/8039\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:35:53Z","timestamp":1760164553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/8039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,27]]},"references-count":175,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22158039"],"URL":"https:\/\/doi.org\/10.3390\/ijms22158039","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,27]]}}}