{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:06:00Z","timestamp":1791327960585,"version":"4.3.1"},"reference-count":95,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T00:00:00Z","timestamp":1374019200000},"content-version":"vor","delay-in-days":808,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell"],"published-print":{"date-parts":[[2011,5]]},"DOI":"10.1016\/j.cell.2011.04.019","type":"journal-article","created":{"date-parts":[[2011,5,21]],"date-time":"2011-05-21T00:28:31Z","timestamp":1305937711000},"page":"513-528","source":"Crossref","is-referenced-by-count":612,"title":["Mapping the NPHP-JBTS-MKS Protein Network Reveals Ciliopathy Disease Genes and Pathways"],"prefix":"10.1016","volume":"145","author":[{"given":"Liyun","family":"Sang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie\u00a0J.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin\u00a0C.","family":"Corbit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel\u00a0H.","family":"Giles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew\u00a0J.","family":"Brauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar\u00a0A.","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa\u00a0M.","family":"Baye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzie\u00a0J.","family":"Scales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik\u00a0G.","family":"Huntzicker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindan\u00a0K.","family":"Sfakianos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Sandoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u00a0Fernando","family":"Bazan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc\u00a0R.","family":"Garcia-Gonzalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen\u00a0D.","family":"Seol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u00a0F.","family":"O'Toole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Held","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko\u00a0M.","family":"Reutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u00a0S.","family":"Lane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad\u00a0Arshad","family":"Rafiq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Noor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ansar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akella\u00a0Radha\u00a0Rama","family":"Devi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00a0C.","family":"Sheffield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane\u00a0C.","family":"Slusarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u00a0B.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u00a0A.","family":"Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedhelm","family":"Hildebrandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy\u00a0F.","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u00a0K.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cell.2011.04.019_bib1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1086\/519494","article-title":"Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome","volume":"81","author":"Baala","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib2","doi-asserted-by":"crossref","first-page":"9784","DOI":"10.1073\/pnas.171269898","article-title":"Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2","volume":"98","author":"Benzing","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.cell.2011.04.019_bib3","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1242\/jcs.028621","article-title":"Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins","volume":"122","author":"Bialas","year":"2009","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.cell.2011.04.019_bib4","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1093\/hmg\/ddl107","article-title":"In-frame deletion in a novel centrosomal\/ciliary protein CEP290\/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse","volume":"15","author":"Chang","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib5","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nature04117","article-title":"Vertebrate Smoothened functions at the primary cilium","volume":"437","author":"Corbit","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.cell.2011.04.019_bib6","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1083\/jcb.201006105","article-title":"CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content","volume":"190","author":"Craige","year":"2010","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.cell.2011.04.019_bib7","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.cub.2007.08.034","article-title":"Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease","volume":"17","author":"Davenport","year":"2007","journal-title":"Curr. Biol."},{"key":"10.1016\/j.cell.2011.04.019_bib8","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.1093\/hmg\/ddp434","article-title":"Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1\/PATJ and Par6","volume":"18","author":"Delous","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib9","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1006\/excr.2000.4822","article-title":"Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells","volume":"256","author":"Donaldson","year":"2000","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.cell.2011.04.019_bib10","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1242\/dev.01663","article-title":"Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut","volume":"132","author":"Essner","year":"2005","journal-title":"Development"},{"key":"10.1016\/j.cell.2011.04.019_bib11","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1681\/ASN.2005121351","article-title":"Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia and photoreceptor connecting cilia","volume":"17","author":"Fliegauf","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.cell.2011.04.019_bib12","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.1073\/pnas.0701361104","article-title":"The human disease network","volume":"104","author":"Goh","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.cell.2011.04.019_bib13","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1681\/ASN.2008050456","article-title":"Nephronophthisis: disease mechanisms of a ciliopathy","volume":"20","author":"Hildebrandt","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.cell.2011.04.019_bib14","doi-asserted-by":"crossref","first-page":"e1000353","DOI":"10.1371\/journal.pgen.1000353","article-title":"A\u00a0systematic approach to mapping recessive disease genes in individuals from outbred populations","volume":"5","author":"Hildebrandt","year":"2009","journal-title":"PLoS Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib15","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature02061","article-title":"Hedgehog signalling in the mouse requires intraflagellar transport proteins","volume":"426","author":"Huangfu","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.cell.2011.04.019_bib16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.nbd.2009.12.022","article-title":"The role of primary cilia in neuronal function","volume":"38","author":"Lee","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.cell.2011.04.019_bib17","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.cell.2006.03.032","article-title":"A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration","volume":"125","author":"Lim","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.cell.2011.04.019_bib18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/79911","article-title":"Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10","volume":"26","author":"Matsuura","year":"2000","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib19","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/ng996","article-title":"The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin","volume":"32","author":"Mollet","year":"2002","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib20","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/hmg\/ddi061","article-title":"Characterization of the nephrocystin\/nephrocystin-4 complex and subcellular localization of nephrocystin-4 to primary cilia and centrosomes","volume":"14","author":"Mollet","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib21","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1002\/humu.21116","article-title":"CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation","volume":"30","author":"Mougou-Zerelli","year":"2009","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.cell.2011.04.019_bib22","first-page":"1373","article-title":"Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinas","volume":"16","author":"Murga-Zamalloa","year":"2010","journal-title":"Mol. Vis."},{"key":"10.1016\/j.cell.2011.04.019_bib23","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cell.2007.03.053","article-title":"A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis","volume":"129","author":"Nachury","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.cell.2011.04.019_bib24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/ng1216","article-title":"Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis","volume":"34","author":"Olbrich","year":"2003","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib25","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/ng1217","article-title":"Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination","volume":"34","author":"Otto","year":"2003","journal-title":"Nat. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib26","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1242\/dev.022228","article-title":"Origin and shaping of the laterality organ in zebrafish","volume":"135","author":"Ote\u00edza","year":"2008","journal-title":"Development"},{"key":"10.1016\/j.cell.2011.04.019_bib27","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/sj.ejhg.5201648","article-title":"Joubert syndrome (and related disorders) (OMIM 213300)","volume":"15","author":"Parisi","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib28","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1083\/jcb.151.3.709","article-title":"Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella","volume":"151","author":"Pazour","year":"2000","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.cell.2011.04.019_bib29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1101\/gad.1363606","article-title":"Tectonic, a novel regulator of the Hedgehog pathway required for both activation and inhibition","volume":"20","author":"Reiter","year":"2006","journal-title":"Genes Dev."},{"key":"10.1016\/j.cell.2011.04.019_bib30","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrm952","article-title":"Intraflagellar transport","volume":"3","author":"Rosenbaum","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cell.2011.04.019_bib31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1136\/jmg.35.6.497","article-title":"Meckel syndrome","volume":"35","author":"Salonen","year":"1998","journal-title":"J. Med. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0092-8674(94)90176-7","article-title":"HNF-3 beta as a regulator of floor plate development","volume":"76","author":"Sasaki","year":"1994","journal-title":"Cell"},{"key":"10.1016\/j.cell.2011.04.019_bib33","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1093\/hmg\/ddn260","article-title":"Genetic and physical interaction between the NPHP5 and NPHP6 gene products","volume":"17","author":"Sch\u00e4fer","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib34","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"10.1016\/j.cell.2011.04.019_bib35","unstructured":"Scholtens, D. (2004). apComplex: Estimate protein complex membership using AP-MS protein data. R package version 2.14.0."},{"key":"10.1016\/j.cell.2011.04.019_bib36","doi-asserted-by":"crossref","first-page":"3548","DOI":"10.1093\/bioinformatics\/bti567","article-title":"Local modeling of global interactome networks","volume":"21","author":"Scholtens","year":"2005","journal-title":"Bioinformatics"},{"key":"10.1016\/j.cell.2011.04.019_bib37","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/cm.20428","article-title":"Inv acts as a molecular anchor for Nphp3 and Nek8 in the proximal segment of primary cilia","volume":"67","author":"Shiba","year":"2010","journal-title":"Cytoskeleton (Hoboken)"},{"key":"10.1016\/j.cell.2011.04.019_bib38","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.cell.2009.04.042","article-title":"Defining the human deubiquitinating enzyme interaction landscape","volume":"138","author":"Sowa","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.cell.2011.04.019_bib39","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.ajhg.2008.05.004","article-title":"Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle","volume":"82","author":"Tallila","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib40","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1002\/pmic.200800873","article-title":"High-throughput generation of tagged stable cell lines for proteomic analysis","volume":"9","author":"Torres","year":"2009","journal-title":"Proteomics"},{"key":"10.1016\/j.cell.2011.04.019_bib41","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/jnr.20807","article-title":"Ataxin 10 induces neuritogenesis via interaction with G-protein beta2 subunit","volume":"83","author":"Waragai","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.cell.2011.04.019_bib42","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1093\/hmg\/ddp422","article-title":"A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling","volume":"18","author":"Weatherbee","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.cell.2011.04.019_bib43","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1091\/mbc.E07-10-1070","article-title":"Functional redundancy of the B9 proteins and nephrocystins in Caenorhabditis elegans ciliogenesis","volume":"19","author":"Williams","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.cell.2011.04.019_bib44","doi-asserted-by":"crossref","first-page":"5575","DOI":"10.1242\/jcs.02665","article-title":"The C. elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception","volume":"118","author":"Winkelbauer","year":"2005","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.cell.2011.04.019_bib45","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1172\/JCI37041","article-title":"Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy","volume":"119","author":"Zaghloul","year":"2009","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.cell.2011.04.019_bib46","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1091\/mbc.E08-07-0772","article-title":"The exocyst protein Sec10 is necessary for primary ciliogenesis and cystogenesis in\u00a0vitro","volume":"20","author":"Zuo","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.cell.2011.04.019_bib47","unstructured":"Alexa A., Rahnenfuhrer J. (2009). topGO: Enrichment analysis for Gene Ontology. R package version 1.16.2."},{"key":"10.1016\/j.cell.2011.04.019_bib48","doi-asserted-by":"crossref","unstructured":"Arts, H.H., Doherty, D., van Beersum, S.E., Parisi, M.A., Letteboer, S.J., Gorden, N.T., Peters, T.A., M\u00e4rker, T., Voesenek, K., Kartono, A., et\u00a0al. (2007). Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome. Nat. Genet. 39, 882\u2013888.","DOI":"10.1038\/ng2069"},{"key":"10.1016\/j.cell.2011.04.019_bib49","doi-asserted-by":"crossref","unstructured":"Attanasio, M., Uhlenhaut, N.H., Sousa, V.H., O'Toole, J.F., Otto, E., Anlag, K., Klugmann, C., Treier, A.C., Helou, J., Sayer, J.A., et\u00a0al. (2007). Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. Nat. Genet. 39, 1018\u20131024.","DOI":"10.1038\/ng2072"},{"key":"10.1016\/j.cell.2011.04.019_bib50","doi-asserted-by":"crossref","unstructured":"Bergmann, C., Fliegauf, M., Br\u00fcchle, N.O., Frank, V., Olbrich, H., Kirschner, J., Schermer, B., Schmedding, I., Kispert, A., Kr\u00e4nzlin, B., et\u00a0al. (2008). Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. Am. J. Hum. Genet. 82, 959\u2013970.","DOI":"10.1016\/j.ajhg.2008.02.017"},{"key":"10.1016\/j.cell.2011.04.019_bib51","doi-asserted-by":"crossref","unstructured":"Bielas, S.L., Silhavy, J.L., Brancati, F., Kisseleva, M.V., Al-Gazali, L., Sztriha, L., Bayoumi, R.A., Zaki, M.S., Abdel-Aleem, A., Rosti, R.O., et\u00a0al. (2009). Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat. Genet. 41, 1032\u20131036.","DOI":"10.1038\/ng.423"},{"key":"10.1016\/j.cell.2011.04.019_bib52","doi-asserted-by":"crossref","unstructured":"Bisgrove, B.W., and Yost, H.J. (2006). The roles of cilia in developmental disorders and disease. Development 133, 4131\u20134143.","DOI":"10.1242\/dev.02595"},{"key":"10.1016\/j.cell.2011.04.019_bib53","doi-asserted-by":"crossref","unstructured":"Boxem, M., Maliga, Z., Klitgord, N., Li, N., Lemmens, I., Mana, M., de Lichtervelde, L., Mul, J.D., van de Peut, D., Devos, M., et\u00a0al. (2008). A protein domain-based interactome network for C. elegans early embryogenesis. Cell 134, 534\u2013545.","DOI":"10.1016\/j.cell.2008.07.009"},{"key":"10.1016\/j.cell.2011.04.019_bib54","doi-asserted-by":"crossref","unstructured":"Briscoe, J., Sussel, L., Serup, P., Hartigan-O'Connor, D., Jessell, T.M., Rubenstein, J.L., and Ericson, J. (1999). Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398, 622\u2013627.","DOI":"10.1038\/19315"},{"key":"10.1016\/j.cell.2011.04.019_bib55","doi-asserted-by":"crossref","unstructured":"Cantagrel, V., Silhavy, J.L., Bielas, S.L., Swistun, D., Marsh, S.E., Bertrand, J.Y., Audollent, S., Atti\u00e9-Bitach, T., Holden, K.R., Dobyns, W.B., et\u00a0al; International Joubert Syndrome Related Disorders Study Group. (2008). Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome. Am. J. Hum. Genet. 83, 170\u2013179.","DOI":"10.1016\/j.ajhg.2008.06.023"},{"key":"10.1016\/j.cell.2011.04.019_bib56","doi-asserted-by":"crossref","unstructured":"Corbit, K.C., Shyer, A.E., Dowdle, W.E., Gaulden, J., Singla, V., Chen, M.H., Chuang, P.T., and Reiter, J.F. (2008). Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat. Cell Biol. 10, 70\u201376.","DOI":"10.1038\/ncb1670"},{"key":"10.1016\/j.cell.2011.04.019_bib57","doi-asserted-by":"crossref","unstructured":"Davis, E.E., Brueckner, M., and Katsanis, N. (2006). The emerging complexity of the vertebrate cilium: new functional roles for an ancient organelle. Dev. Cell 11, 9\u201319.","DOI":"10.1016\/j.devcel.2006.06.009"},{"key":"10.1016\/j.cell.2011.04.019_bib58","doi-asserted-by":"crossref","unstructured":"Dessaud, E., McMahon, A.P., and Briscoe, J. (2008). Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network. Development 135, 2489\u20132503.","DOI":"10.1242\/dev.009324"},{"key":"10.1016\/j.cell.2011.04.019_bib59","doi-asserted-by":"crossref","unstructured":"Dixon-Salazar, T., Silhavy, J.L., Marsh, S.E., Louie, C.M., Scott, L.C., Gururaj, A., Al-Gazali, L., Al-Tawari, A.A., Kayserili, H., Sztriha, L., and Gleeson, J.G. (2004). Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. Am. J. Hum. Genet. 75, 979\u2013987.","DOI":"10.1086\/425985"},{"key":"10.1016\/j.cell.2011.04.019_bib60","doi-asserted-by":"crossref","unstructured":"Donaldson, J.C., Dise, R.S., Ritchie, M.D., and Hanks, S.K. (2002). Nephrocystin-conserved domains involved in targeting to epithelial cell-cell junctions, interaction with filamins, and establishing cell polarity. J. Biol. Chem. 277, 29028\u201329035.","DOI":"10.1074\/jbc.M111697200"},{"key":"10.1016\/j.cell.2011.04.019_bib61","doi-asserted-by":"crossref","unstructured":"Ericson, J., Rashbass, P., Schedl, A., Brenner-Morton, S., Kawakami, A., van Heyningen, V., Jessell, T.M., and Briscoe, J. (1997). Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90, 169\u2013180.","DOI":"10.1016\/S0092-8674(00)80323-2"},{"key":"10.1016\/j.cell.2011.04.019_bib62","doi-asserted-by":"crossref","unstructured":"Evangelista, M., Lim, T.Y., Lee, J., Parker, L., Ashique, A., Peterson, A.S., Ye, W., Davis, D.P., and de Sauvage, F.J. (2008). Kinome siRNA screen identifies regulators of ciliogenesis and hedgehog signal transduction. Sci. Signal. 1, ra7.","DOI":"10.1126\/scisignal.1162925"},{"key":"10.1016\/j.cell.2011.04.019_bib63","doi-asserted-by":"crossref","unstructured":"Frank-Kamenetsky, M., Zhang, X.M., Bottega, S., Guicherit, O., Wichterle, H., Dudek, H., Bumcrot, D., Wang, F.Y., Jones, S., Shulok, J., et\u00a0al. (2002). Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists. J. Biol. 1, 10.","DOI":"10.1186\/1475-4924-1-10"},{"key":"10.1016\/j.cell.2011.04.019_bib64","doi-asserted-by":"crossref","unstructured":"Gorden, N.T., Arts, H.H., Parisi, M.A., Coene, K.L.M., Letteboer, S.J.F., van Beersum, S.E.C., Mans, D.A., Hikida, A., Eckert, M., Knutzen, D., et\u00a0al. (2008). CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. Am. J. Hum. Genet. 83, 559\u2013571.","DOI":"10.1016\/j.ajhg.2008.10.002"},{"key":"10.1016\/j.cell.2011.04.019_bib65","doi-asserted-by":"crossref","unstructured":"Hildebrandt, F., Heeringa, S.F., R\u00fcschendorf, F., Attanasio, M., N\u00fcrnberg, G., Becker, C., Seelow, D., Huebner, N., Chernin, G., Vlangos, C.N., et\u00a0al. (2009). A systematic approach to mapping recessive disease genes in individuals from outbred populations. PLoS Genet. 5, e1000353.","DOI":"10.1371\/journal.pgen.1000353"},{"key":"10.1016\/j.cell.2011.04.019_bib66","doi-asserted-by":"crossref","unstructured":"Hildebrandt, F., and Otto, E. (2005). Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat. Rev. Genet. 6, 928\u2013940.","DOI":"10.1038\/nrg1727"},{"key":"10.1016\/j.cell.2011.04.019_bib67","doi-asserted-by":"crossref","unstructured":"Hildebrandt, F., Otto, E., Rensing, C., Nothwang, H.G., Vollmer, M., Adolphs, J., Hanusch, H., and Brandis, M. (1997). A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nat. Genet. 17, 149\u2013153.","DOI":"10.1038\/ng1097-149"},{"key":"10.1016\/j.cell.2011.04.019_bib68","doi-asserted-by":"crossref","unstructured":"Hildebrandt, F., and Zhou, W. (2007). Nephronophthisis-associated ciliopathies. J. Am. Soc. Nephrol. 18, 1855\u20131871.","DOI":"10.1681\/ASN.2006121344"},{"key":"10.1016\/j.cell.2011.04.019_bib69","doi-asserted-by":"crossref","unstructured":"Jacoby, M., Cox, J.J., Gayral, S., Hampshire, D.J., Ayub, M., Blockmans, M., Pernot, E., Kisseleva, M.V., Comp\u00e8re, P., Schiffmann, S.N., et\u00a0al. (2009). INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat. Genet. 41, 1027\u20131031.","DOI":"10.1038\/ng.427"},{"key":"10.1016\/j.cell.2011.04.019_bib70","doi-asserted-by":"crossref","unstructured":"Kytt\u00e4l\u00e4, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., and Kestil\u00e4, M. (2006). MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome. Nat. Genet. 38, 155\u2013157.","DOI":"10.1038\/ng1714"},{"key":"10.1016\/j.cell.2011.04.019_bib71","doi-asserted-by":"crossref","unstructured":"Lancaster, M.A., Louie, C.M., Silhavy, J.L., Sintasath, L., Decambre, M., Nigam, S.K., Willert, K., and Gleeson, J.G. (2009). Impaired Wnt-beta-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy. Nat. Med. 15, 1046\u20131054.","DOI":"10.1038\/nm.2010"},{"key":"10.1016\/j.cell.2011.04.019_bib72","doi-asserted-by":"crossref","unstructured":"Letunic, I., Doerks, T., and Bork, P. (2009). SMART 6: recent updates and new developments. Nucleic Acids Res. 37 (Database issue), D229\u2013D232.","DOI":"10.1093\/nar\/gkn808"},{"key":"10.1016\/j.cell.2011.04.019_bib73","doi-asserted-by":"crossref","unstructured":"McGuffin, L.J., Bryson, K., and Jones, D.T. (2000). The PSIPRED protein structure prediction server. Bioinformatics 16, 404\u2013405.","DOI":"10.1093\/bioinformatics\/16.4.404"},{"key":"10.1016\/j.cell.2011.04.019_bib74","doi-asserted-by":"crossref","unstructured":"Novick, P., Field, C., and Schekman, R. (1980). Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21, 205\u2013215.","DOI":"10.1016\/0092-8674(80)90128-2"},{"key":"10.1016\/j.cell.2011.04.019_bib75","doi-asserted-by":"crossref","unstructured":"O'Brien, L.E., Zegers, M.M., and Mostov, K.E. (2002). Opinion: Building epithelial architecture: insights from three-dimensional culture models. Nat. Rev. Mol. Cell Biol. 3, 531\u2013537.","DOI":"10.1038\/nrm859"},{"key":"10.1016\/j.cell.2011.04.019_bib76","doi-asserted-by":"crossref","unstructured":"Otto, E., Hoefele, J., Ruf, R., Mueller, A.M., Hiller, K.S., Wolf, M.T., Schuermann, M.J., Becker, A., Birkenh\u00e4ger, R., Sudbrak, R., et\u00a0al. (2002). A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. Am. J. Hum. Genet. 71, 1161\u20131167.","DOI":"10.1086\/344395"},{"key":"10.1016\/j.cell.2011.04.019_bib77","doi-asserted-by":"crossref","unstructured":"Otto, E.A., Loeys, B., Khanna, H., Hellemans, J., Sudbrak, R., Fan, S., Muerb, U., O'Toole, J.F., Helou, J., Attanasio, M., et\u00a0al. (2005). Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Nat. Genet. 37, 282\u2013288.","DOI":"10.1038\/ng1520"},{"key":"10.1016\/j.cell.2011.04.019_bib78","doi-asserted-by":"crossref","unstructured":"Otto, E.A., Trapp, M.L., Schultheiss, U.T., Helou, J., Quarmby, L.M., and Hildebrandt, F. (2008). NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. J. Am. Soc. Nephrol. 19, 587\u2013592.","DOI":"10.1681\/ASN.2007040490"},{"key":"10.1016\/j.cell.2011.04.019_bib79","doi-asserted-by":"crossref","unstructured":"Parisi, M.A., Bennett, C.L., Eckert, M.L., Dobyns, W.B., Gleeson, J.G., Shaw, D.W., McDonald, R., Eddy, A., Chance, P.F., and Glass, I.A. (2004). The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome. Am. J. Hum. Genet. 75, 82\u201391.","DOI":"10.1086\/421846"},{"key":"10.1016\/j.cell.2011.04.019_bib80","doi-asserted-by":"crossref","unstructured":"Praetorius, H.A., and Spring, K.R. (2003). The renal cell primary cilium functions as a flow sensor. Curr. Opin. Nephrol. Hypertens. 12, 517\u2013520.","DOI":"10.1097\/00041552-200309000-00006"},{"key":"10.1016\/j.cell.2011.04.019_bib81","doi-asserted-by":"crossref","unstructured":"Ross, A.J., May-Simera, H., Eichers, E.R., Kai, M., Hill, J., Jagger, D.J., Leitch, C.C., Chapple, J.P., Munro, P.M., Fisher, S., et\u00a0al. (2005). Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat. Genet. 37, 1135\u20131140.","DOI":"10.1038\/ng1644"},{"key":"10.1016\/j.cell.2011.04.019_bib82","doi-asserted-by":"crossref","unstructured":"Rual, J.F., Venkatesan, K., Hao, T., Hirozane-Kishikawa, T., Dricot, A., Li, N., Berriz, G.F., Gibbons, F.D., Dreze, M., Ayivi-Guedehoussou, N., et\u00a0al. (2005). Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173\u20131178.","DOI":"10.1038\/nature04209"},{"key":"10.1016\/j.cell.2011.04.019_bib83","doi-asserted-by":"crossref","unstructured":"Sayer, J.A., Otto, E.A., O'Toole, J.F., Nurnberg, G., Kennedy, M.A., Becker, C., Hennies, H.C., Helou, J., Attanasio, M., Fausett, B.V., et\u00a0al. (2006). The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat. Genet. 38, 674\u2013681.","DOI":"10.1038\/ng1786"},{"key":"10.1016\/j.cell.2011.04.019_bib84","doi-asserted-by":"crossref","unstructured":"Simons, M., Gloy, J., Ganner, A., Bullerkotte, A., Bashkurov, M., Kr\u00f6nig, C., Schermer, B., Benzing, T., Cabello, O.A., Jenny, A., et\u00a0al. (2005). Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat. Genet. 37, 537\u2013543.","DOI":"10.1038\/ng1552"},{"key":"10.1016\/j.cell.2011.04.019_bib85","doi-asserted-by":"crossref","unstructured":"Smith, U.M., Consugar, M., Tee, L.J., McKee, B.M., Maina, E.N., Whelan, S., Morgan, N.V., Goranson, E., Gissen, P., Lilliquist, S., et\u00a0al. (2006). The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat. Genet. 38, 191\u2013196.","DOI":"10.1038\/ng1713"},{"key":"10.1016\/j.cell.2011.04.019_bib86","doi-asserted-by":"crossref","unstructured":"S\u00f6ding, J. (2005). Protein homology detection by HMM-HMM comparison. Bioinformatics 21, 951\u2013960.","DOI":"10.1093\/bioinformatics\/bti125"},{"key":"10.1016\/j.cell.2011.04.019_bib87","doi-asserted-by":"crossref","unstructured":"Spektor, A., Tsang, W.Y., Khoo, D., and Dynlacht, B.D. (2007). Cep97 and CP110 suppress a cilia assembly program. Cell 130, 678\u2013690.","DOI":"10.1016\/j.cell.2007.06.027"},{"key":"10.1016\/j.cell.2011.04.019_bib88","doi-asserted-by":"crossref","unstructured":"Tanabe, Y., Roelink, H., and Jessell, T.M. (1995). Induction of motor neurons by Sonic hedgehog is independent of floor plate differentiation. Curr. Biol. 5, 651\u2013658.","DOI":"10.1016\/S0960-9822(95)00130-8"},{"key":"10.1016\/j.cell.2011.04.019_bib89","doi-asserted-by":"crossref","unstructured":"Torres, J.Z., Miller, J.J., and Jackson, P.K. (2009). High-throughput generation of tagged stable cell lines for proteomic analysis. Proteomics 9, 2888\u20132891.","DOI":"10.1002\/pmic.200800873"},{"key":"10.1016\/j.cell.2011.04.019_bib90","doi-asserted-by":"crossref","unstructured":"Tsang, W.Y., Bossard, C., Khanna, H., Per\u00e4nen, J., Swaroop, A., Malhotra, V., and Dynlacht, B.D. (2008). CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Dev. Cell 15, 187\u2013197.","DOI":"10.1016\/j.devcel.2008.07.004"},{"key":"10.1016\/j.cell.2011.04.019_bib91","doi-asserted-by":"crossref","unstructured":"Valente, E.M., Logan, C.V., Mougou-Zerelli, S., Lee, J.H., Silhavy, J.L., Brancati, F., Iannicelli, M., Travaglini, L., Romani, S., Illi, B., et\u00a0al. (2010). Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat. Genet. 42, 619\u2013625.","DOI":"10.1038\/ng.594"},{"key":"10.1016\/j.cell.2011.04.019_bib92","doi-asserted-by":"crossref","unstructured":"Wang, B., Fallon, J.F., and Beachy, P.A. (2000). Hedgehog-regulated processing of Gli3 produces an anterior\/posterior repressor gradient in the developing vertebrate limb. Cell 100, 423\u2013434.","DOI":"10.1016\/S0092-8674(00)80678-9"},{"key":"10.1016\/j.cell.2011.04.019_bib93","doi-asserted-by":"crossref","unstructured":"Wolfrum, U., and Schmitt, A. (2000). Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells. Cell Motil. Cytoskeleton 46, 95\u2013107.","DOI":"10.1002\/1097-0169(200006)46:2<95::AID-CM2>3.0.CO;2-Q"},{"key":"10.1016\/j.cell.2011.04.019_bib94","doi-asserted-by":"crossref","unstructured":"Wu, S., and Zhang, Y. (2008). MUSTER: Improving protein sequence profile-profile alignments by using multiple sources of structure information. Proteins 72, 547\u2013556.","DOI":"10.1002\/prot.21945"},{"key":"10.1016\/j.cell.2011.04.019_bib95","doi-asserted-by":"crossref","unstructured":"Zhou, W., Dai, J., Attanasio, M., and Hildebrandt, F. (2010). Nephrocystin-3 is required for ciliary function in zebrafish embryos. Am. J. Physiol. Renal Physiol. 299, F55\u2013F62.","DOI":"10.1152\/ajprenal.00043.2010"}],"container-title":["Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867411004776?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867411004776?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T18:57:43Z","timestamp":1712429863000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0092867411004776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":95,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["S0092867411004776"],"URL":"https:\/\/doi.org\/10.1016\/j.cell.2011.04.019","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.11146956.12119055","asserted-by":"object"}]},"ISSN":["0092-8674"],"issn-type":[{"value":"0092-8674","type":"print"}],"subject":[],"published":{"date-parts":[[2011,5]]}}}