{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:41:44Z","timestamp":1781113304457,"version":"3.54.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006356","name":"Syddansk Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004196","name":"Odense Universitetshospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Unexplained or idiopathic ketotic hypoglycemia (KH) is the most common type of hypoglycemia in children. The diagnosis is based on the exclusion of routine hormonal and metabolic causes of hypoglycemia. We aimed to identify novel genes that cause KH, as this may lead to a more targeted treatment. Deep phenotyping of ten preschool age at onset KH patients (boys, n\u2009=\u20095; girls, n\u2009=\u20095) was performed followed by trio exome sequencing and comprehensive bioinformatics analysis. Data analysis revealed four novel candidate genes: (1) <jats:italic>NCOR1<\/jats:italic> in a patient with KH, iron deficiency and loose stools; (2) <jats:italic>IGF2BP1<\/jats:italic> in a proband with KH, short stature and delayed bone age; (3) <jats:italic>SLC5A2<\/jats:italic> in a proband with KH, intermittent glucosuria and extremely elevated p-GLP-1; and (4) <jats:italic>NEK11<\/jats:italic> in a proband with ketotic hypoglycemia and liver affliction. These genes are associated with different metabolic processes, such as gluconeogenesis, translational regulation, and glucose transport. In conclusion, WES identified DNA variants in four different genes as potential novel causes of IKH, suggesting that IKH is a heterogeneous disorder that can be split into several novel diseases: NCOR1-KH, IGF2BP1-KH, SGLT2-KH or familial renal glucosuria KH, and NEK11-KH. Precision medicine treatment based on exome sequencing may lead to advances in the management of IKH.<\/jats:p>","DOI":"10.1038\/s41598-020-58845-3","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T11:03:42Z","timestamp":1581073422000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exome sequencing revealed DNA variants in NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes of ketotic hypoglycemia in children"],"prefix":"10.1038","volume":"10","author":[{"given":"Yazeid","family":"Alhaidan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4107-8771","authenticated-orcid":false,"given":"Martin J.","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders J\u00f8rgen","family":"Schou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria H.","family":"Stenlid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-0390","authenticated-orcid":false,"given":"Mohammed A.","family":"Al Balwi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Thybo","family":"Christesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Brusgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"key":"58845_CR1","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1542\/peds.105.5.1141","volume":"105","author":"M Cornblath","year":"2000","unstructured":"Cornblath, M. et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 105, 1141\u20131145 (2000).","journal-title":"Pediatrics"},{"key":"58845_CR2","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.jpeds.2015.03.057","volume":"167","author":"PS Thornton","year":"2015","unstructured":"Thornton, P. S. et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J. Pediatr. 167, 238\u2013245, https:\/\/doi.org\/10.1016\/j.jpeds.2015.03.057 (2015).","journal-title":"J. Pediatr."},{"key":"58845_CR3","first-page":"1681","volume":"157","author":"UM Andersen","year":"1995","unstructured":"Andersen, U. M. & Lund, H. T. [Hypoglycemia caused by growth hormone deficiency. Two cases in children with cerebral paresis]. Ugeskr. Laeger 157, 1681\u20131682 (1995).","journal-title":"Two cases in children with cerebral paresis]. Ugeskr. Laeger"},{"key":"58845_CR4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ymgme.2004.02.004","volume":"82","author":"MJ Bennett","year":"2004","unstructured":"Bennett, M. J., Boriack, R. L., Narayan, S., Rutledge, S. L. & Raff, M. L. Novel mutations in CPT 1A define molecular heterogeneity of hepatic carnitine palmitoyltransferase I deficiency. Mol. Genet. Metab. 82, 59\u201363, https:\/\/doi.org\/10.1016\/j.ymgme.2004.02.004 (2004).","journal-title":"Mol. Genet. Metab."},{"key":"58845_CR5","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/humu.20085","volume":"24","author":"V Iacobazzi","year":"2004","unstructured":"Iacobazzi, V. et al. Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency. Hum. Mutat. 24, 312\u2013320, https:\/\/doi.org\/10.1002\/humu.20085 (2004).","journal-title":"Hum. Mutat."},{"key":"58845_CR6","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.3748\/wjg.v13.i18.2541","volume":"13","author":"H Ozen","year":"2007","unstructured":"Ozen, H. Glycogen storage diseases: new perspectives. World J. Gastroenterol. 13, 2541\u20132553, https:\/\/doi.org\/10.3748\/wjg.v13.i18.2541 (2007).","journal-title":"World J. Gastroenterol."},{"key":"58845_CR7","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.pcl.2017.11.005","volume":"65","author":"DA Weinstein","year":"2018","unstructured":"Weinstein, D. A., Steuerwald, U., De Souza, C. F. M. & Derks, T. G. J. Inborn Errors of Metabolism with Hypoglycemia: Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis. Pediatr. Clin. North Am. 65, 247\u2013265, https:\/\/doi.org\/10.1016\/j.pcl.2017.11.005 (2018).","journal-title":"Pediatr. Clin. North Am."},{"key":"58845_CR8","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1258\/acb.2011.011012","volume":"48","author":"TF Lang","year":"2011","unstructured":"Lang, T. F. Update on investigating hypoglycaemia in childhood. Ann. Clin. Biochem. 48, 200\u2013211, https:\/\/doi.org\/10.1258\/acb.2011.011012 (2011).","journal-title":"Ann. Clin. Biochem."},{"key":"58845_CR9","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0300-595X(82)80041-8","volume":"11","author":"A Aynsley-Green","year":"1982","unstructured":"Aynsley-Green, A. Hypoglycaemia in infants and children. Clin. Endocrinol. Metab. 11, 159\u2013194 (1982).","journal-title":"Clin. Endocrinol. Metab."},{"key":"58845_CR10","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/0736-4679(93)90306-R","volume":"11","author":"ES Pollack","year":"1993","unstructured":"Pollack, E. S. & Pollack, C. V. Jr. Ketotic hypoglycemia: a case report. J. Emerg. Med. 11, 531\u2013534 (1993).","journal-title":"J. Emerg. Med."},{"key":"58845_CR11","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0736-4679(03)00100-8","volume":"25","author":"LP Daly","year":"2003","unstructured":"Daly, L. P., Osterhoudt, K. C. & Weinzimer, S. A. Presenting features of idiopathic ketotic hypoglycemia. J. Emerg. Med. 25, 39\u201343 (2003).","journal-title":"J. Emerg. Med."},{"key":"58845_CR12","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/S0022-3476(64)80611-9","volume":"64","author":"E Colle","year":"1964","unstructured":"Colle, E. & Ulstrom, R. A. Ketotic hypoglycemia. The Journal of Pediatrics 64, 632\u2013651, https:\/\/doi.org\/10.1016\/S0022-3476(64)80611-9 (1964).","journal-title":"The Journal of Pediatrics"},{"key":"58845_CR13","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s00431-007-0598-5","volume":"167","author":"HH Huidekoper","year":"2008","unstructured":"Huidekoper, H. H. et al. Fasting adaptation in idiopathic ketotic hypoglycemia: a mismatch between glucose production and demand. Eur. J. Pediatr. 167, 859\u2013865, https:\/\/doi.org\/10.1007\/s00431-007-0598-5 (2008).","journal-title":"Eur. J. Pediatr."},{"key":"58845_CR14","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/S0300-595X(83)80051-6","volume":"12","author":"MW Haymond","year":"1983","unstructured":"Haymond, M. W. & Pagliara, A. S. Ketotic hypoglycaemia. Clin. Endocrinol. Metab. 12, 447\u2013462 (1983).","journal-title":"Clin. Endocrinol. Metab."},{"key":"58845_CR15","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1097\/00006565-199808000-00006","volume":"14","author":"J Pershad","year":"1998","unstructured":"Pershad, J., Monroe, K. & Atchison, J. Childhood hypoglycemia in an urban emergency department: epidemiology and a diagnostic approach to the problem. Pediatr. Emerg. Care 14, 268\u2013271 (1998).","journal-title":"Pediatr. Emerg. Care"},{"issue":"1","key":"58845_CR16","doi-asserted-by":"publisher","first-page":"nrs.08001","DOI":"10.1621\/nrs.08001","volume":"8","author":"Lei Yin","year":"2010","unstructured":"Yin, L., Wu, N. & Lazar, M. A. Nuclear receptor Rev-erb\u03b1: a heme receptor that coordinates circadian rhythm and metabolism. Nuclear Receptor Signaling 8, https:\/\/doi.org\/10.1621\/nrs.08001 (2010).","journal-title":"Nuclear Receptor Signaling"},{"key":"58845_CR17","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/S0092-8674(00)00064-7","volume":"102","author":"K Jepsen","year":"2000","unstructured":"Jepsen, K. et al. Combinatorial roles of the nuclear receptor corepressor in transcription and development. Cell 102, 753\u2013763 (2000).","journal-title":"Cell"},{"key":"58845_CR18","doi-asserted-by":"publisher","first-page":"7202","DOI":"10.1073\/pnas.97.13.7202","volume":"97","author":"YD Wen","year":"2000","unstructured":"Wen, Y. D. et al. The histone deacetylase-3 complex contains nuclear receptor corepressors. Proc. Natl. Acad. Sci. USA 97, 7202\u20137207 (2000).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"58845_CR19","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1126\/science.1150179","volume":"318","author":"L Yin","year":"2007","unstructured":"Yin, L. et al. Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science 318, 1786\u20131789, https:\/\/doi.org\/10.1126\/science.1150179 (2007).","journal-title":"Science"},{"key":"58845_CR20","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.cell.2009.06.049","volume":"138","author":"Z Wang","year":"2009","unstructured":"Wang, Z. et al. Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138, 1019\u20131031, https:\/\/doi.org\/10.1016\/j.cell.2009.06.049 (2009).","journal-title":"Cell"},{"key":"58845_CR21","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.cell.2011.03.043","volume":"145","author":"MM Mihaylova","year":"2011","unstructured":"Mihaylova, M. M. et al. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell 145, 607\u2013621, https:\/\/doi.org\/10.1016\/j.cell.2011.03.043 (2011).","journal-title":"Cell"},{"key":"58845_CR22","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/nature07541","volume":"456","author":"T Alenghat","year":"2008","unstructured":"Alenghat, T. et al. Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology. Nature 456, 997\u20131000, https:\/\/doi.org\/10.1038\/nature07541 (2008).","journal-title":"Nature"},{"key":"58845_CR23","doi-asserted-by":"publisher","unstructured":"Pasricha, S. R. et al. Hepcidin is regulated by promoter-associated histone acetylation and HDAC3. Nature Communications 8, https:\/\/doi.org\/10.1038\/s41467-017-00500-z (2017).","DOI":"10.1038\/s41467-017-00500-z"},{"key":"58845_CR24","doi-asserted-by":"publisher","first-page":"4596","DOI":"10.1073\/pnas.072632499","volume":"99","author":"G Nicolas","year":"2002","unstructured":"Nicolas, G. et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc. Natl. Acad. Sci. USA 99, 4596\u20134601, https:\/\/doi.org\/10.1073\/pnas.072632499 (2002).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"58845_CR25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1006\/mgme.2000.3066","volume":"71","author":"J Vockley","year":"2000","unstructured":"Vockley, J., Rinaldo, P., Bennett, M. J., Matern, D. & Vladutiu, G. D. Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways. Mol. Genet. Metab. 71, 10\u201318, https:\/\/doi.org\/10.1006\/mgme.2000.3066 (2000).","journal-title":"Mol. Genet. Metab."},{"key":"58845_CR26","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2015.06.018","volume":"53","author":"M Almuqbil","year":"2015","unstructured":"Almuqbil, M. et al. New Paradigm for the Treatment of Glucose Transporter 1 Deficiency Syndrome: Low Glycemic Index Diet and Modified High Amylopectin Cornstarch. Pediatr. Neurol. 53, 243\u2013246, https:\/\/doi.org\/10.1016\/j.pediatrneurol.2015.06.018 (2015).","journal-title":"Pediatr. Neurol."},{"key":"58845_CR27","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1101\/gad.1862910","volume":"24","author":"JA Chao","year":"2010","unstructured":"Chao, J. A. et al. ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes Dev. 24, 148\u2013158, https:\/\/doi.org\/10.1101\/gad.1862910 (2010).","journal-title":"Genes Dev."},{"key":"58845_CR28","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1128\/MCB.19.2.1262","volume":"19","author":"J Nielsen","year":"1999","unstructured":"Nielsen, J. et al. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol. Cell. Biol. 19, 1262\u20131270 (1999).","journal-title":"Mol. Cell. Biol."},{"key":"58845_CR29","doi-asserted-by":"publisher","first-page":"4368","DOI":"10.1093\/nar\/gkh754","volume":"32","author":"J Nielsen","year":"2004","unstructured":"Nielsen, J., Kristensen, M. A., Willemoes, M., Nielsen, F. C. & Christiansen, J. Sequential dimerization of human zipcode-binding protein IMP1 on RNA: a cooperative mechanism providing RNP stability. Nucleic Acids Res. 32, 4368\u20134376, https:\/\/doi.org\/10.1093\/nar\/gkh754 (2004).","journal-title":"Nucleic Acids Res."},{"key":"58845_CR30","doi-asserted-by":"publisher","first-page":"3777","DOI":"10.1073\/pnas.94.8.3777","volume":"94","author":"A Morrione","year":"1997","unstructured":"Morrione, A. et al. Insulin-like growth factor II stimulates cell proliferation through the insulin receptor. Proc. Natl. Acad. Sci. USA 94, 3777\u20133782 (1997).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"58845_CR31","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1006\/dbio.1997.8666","volume":"189","author":"A Louvi","year":"1997","unstructured":"Louvi, A., Accili, D. & Efstratiadis, A. Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development. Dev. Biol. 189, 33\u201348, https:\/\/doi.org\/10.1006\/dbio.1997.8666 (1997).","journal-title":"Dev. Biol."},{"key":"58845_CR32","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1111\/j.1365-2796.1993.tb01012.x","volume":"234","author":"J Zapf","year":"1993","unstructured":"Zapf, J. Role of insulin-like growth factor (IGF) II and IGF binding proteins in extrapancreatic tumour hypoglycaemia. J. Intern. Med. 234, 543\u2013552 (1993).","journal-title":"J. Intern. Med."},{"key":"58845_CR33","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1172\/jci115803","volume":"89","author":"RC Eastman","year":"1992","unstructured":"Eastman, R. C. et al. Glucose utilization in a patient with hepatoma and hypoglycemia. Assessment by a positron emission tomography. J. Clin. Invest. 89, 1958\u20131963, https:\/\/doi.org\/10.1172\/jci115803 (1992).","journal-title":"Assessment by a positron emission tomography. J. Clin. Invest."},{"key":"58845_CR34","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/BF00404019","volume":"34","author":"N Moller","year":"1991","unstructured":"Moller, N. et al. Basal and insulin stimulated substrate metabolism in tumour induced hypoglycaemia; evidence for increased muscle glucose uptake. Diabetologia 34, 17\u201320 (1991).","journal-title":"Diabetologia"},{"key":"58845_CR35","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1172\/jci114619","volume":"85","author":"ET Shapiro","year":"1990","unstructured":"Shapiro, E. T. et al. Tumor hypoglycemia: relationship to high molecular weight insulin-like growth factor-II. J. Clin. Invest. 85, 1672\u20131679, https:\/\/doi.org\/10.1172\/jci114619 (1990).","journal-title":"J. Clin. Invest."},{"key":"58845_CR36","doi-asserted-by":"publisher","first-page":"4448","DOI":"10.1128\/mcb.24.10.4448-4464.2004","volume":"24","author":"TVO Hansen","year":"2004","unstructured":"Hansen, T. V. O. et al. Dwarfism and Impaired Gut Development in Insulin-Like Growth Factor II mRNA-Binding Protein 1-Deficient Mice. Mol. Cell. Biol. 24, 4448\u20134464, https:\/\/doi.org\/10.1128\/mcb.24.10.4448-4464.2004 (2004).","journal-title":"Mol. Cell. Biol."},{"issue":"1","key":"58845_CR37","doi-asserted-by":"publisher","first-page":"e0146114","DOI":"10.1371\/journal.pone.0146114","volume":"11","author":"Emilia Ottosson-Laakso","year":"2016","unstructured":"Ottosson-Laakso, E. et al. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time. PLoS One 11, https:\/\/doi.org\/10.1371\/journal.pone.0146114 (2016).","journal-title":"PLOS ONE"},{"key":"58845_CR38","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1097\/01.ASN.0000092790.89332.D2","volume":"14","author":"R Santer","year":"2003","unstructured":"Santer, R. et al. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J. Am. Soc. Nephrol. 14, 2873\u20132882 (2003).","journal-title":"J. Am. Soc. Nephrol."},{"key":"58845_CR39","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s00439-010-0927-z","volume":"129","author":"L Yu","year":"2011","unstructured":"Yu, L. et al. Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients. Hum. Genet. 129, 335\u2013344, https:\/\/doi.org\/10.1007\/s00439-010-0927-z (2011).","journal-title":"Hum. Genet."},{"key":"58845_CR40","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nm.3828","volume":"21","author":"C Bonner","year":"2015","unstructured":"Bonner, C. et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat. Med. 21, 512\u2013517, https:\/\/doi.org\/10.1038\/nm.3828 (2015).","journal-title":"Nat. Med."},{"key":"58845_CR41","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1530\/joe-11-0094","volume":"211","author":"NM Whalley","year":"2011","unstructured":"Whalley, N. M., Pritchard, L. E., Smith, D. M. & White, A. Processing of proglucagon to GLP-1 in pancreatic alpha-cells: is this a paracrine mechanism enabling GLP-1 to act on beta-cells? J. Endocrinol. 211, 99\u2013106, https:\/\/doi.org\/10.1530\/joe-11-0094 (2011).","journal-title":"J. Endocrinol."},{"key":"58845_CR42","doi-asserted-by":"publisher","first-page":"e0187836","DOI":"10.1371\/journal.pone.0187836","volume":"12","author":"V Sancho","year":"2017","unstructured":"Sancho, V. et al. Metabolic regulation of GLP-1 and PC1\/3 in pancreatic alpha-cell line. PLoS One 12, e0187836, https:\/\/doi.org\/10.1371\/journal.pone.0187836 (2017).","journal-title":"PLoS One"},{"key":"58845_CR43","doi-asserted-by":"publisher","first-page":"39655","DOI":"10.1074\/jbc.M204599200","volume":"277","author":"K Noguchi","year":"2002","unstructured":"Noguchi, K., Fukazawa, H., Murakami, Y. & Uehara, Y. Nek11, a new member of the NIMA family of kinases, involved in DNA replication and genotoxic stress responses. J. Biol. Chem. 277, 39655\u201339665, https:\/\/doi.org\/10.1074\/jbc.M204599200 (2002).","journal-title":"J. Biol. Chem."},{"key":"58845_CR44","doi-asserted-by":"publisher","first-page":"D802","DOI":"10.1093\/nar\/gkt977","volume":"42","author":"G Koscielny","year":"2014","unstructured":"Koscielny, G. et al. The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data. Nucleic Acids Res. 42, D802\u2013809, https:\/\/doi.org\/10.1093\/nar\/gkt977 (2014).","journal-title":"Nucleic Acids Res."},{"key":"58845_CR45","doi-asserted-by":"publisher","unstructured":"Karczewski, K. J. et al. Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv, 531210, https:\/\/doi.org\/10.1101\/531210 (2019).","DOI":"10.1101\/531210"},{"issue":"7616","key":"58845_CR46","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature19057","volume":"536","author":"Monkol Lek","year":"2016","unstructured":"Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285, https:\/\/doi.org\/10.1038\/nature19057, https:\/\/www.nature.com\/articles\/nature19057#supplementary-information (2016).","journal-title":"Nature"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58845-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58845-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58845-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T06:36:18Z","timestamp":1670308578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-58845-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,7]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["58845"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-58845-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,7]]},"assertion":[{"value":"16 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2114"}}