{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:36:17Z","timestamp":1790721377463,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01ES025435; R21CA216867"],"award-info":[{"award-number":["K01ES025435; R21CA216867"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spectrum Health-Michigan State University Alliance Corporation","award":["To CPB and ASB"],"award-info":[{"award-number":["To CPB and ASB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Ornithine decarboxylase 1 (ODC1 gene) has been linked through gain-of-function variants to a rare disease featuring developmental delay, alopecia, macrocephaly, and structural brain anomalies. ODC1 has been linked to additional diseases like cancer, with growing evidence for neurological contributions to schizophrenia, mood disorders, anxiety, epilepsy, learning, and suicidal behavior. The evidence of ODC1 connection to neural disorders highlights the need for a systematic analysis of ODC1 genotype-to-phenotype associations. An analysis of variants from ClinVar, Geno2MP, TOPMed, gnomAD, and COSMIC revealed an intellectual disability and seizure connected loss-of-function variant, ODC G84R (rs138359527, NC_000002.12:g.10444500C &gt; T). The missense variant is found in ~1% of South Asian individuals and results in 2.5-fold decrease in enzyme function. Expression quantitative trait loci (eQTLs) reveal multiple functionally annotated, non-coding variants regulating ODC1 that associate with psychiatric\/neurological phenotypes. Further dissection of RNA-Seq during fetal brain development and within cerebral organoids showed an association of ODC1 expression with cell proliferation of neural progenitor cells, suggesting gain-of-function variants with neural over-proliferation and loss-of-function variants with neural depletion. The linkage from the expression data of ODC1 in early neural progenitor proliferation to phenotypes of neurodevelopmental delay and to the connection of polyamine metabolites in brain function establish ODC1 as a bona fide neurodevelopmental disorder gene.<\/jats:p>","DOI":"10.3390\/genes12040470","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T14:51:12Z","timestamp":1616683872000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development"],"prefix":"10.3390","volume":"12","author":[{"given":"Jeremy W.","family":"Prokop","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Center for Research in Autism, Intellectual, and Other Neurodevelopmental Disabilities, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4255-0396","authenticated-orcid":false,"given":"Caleb P.","family":"Bupp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Spectrum Health Medical Genetics, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Frisch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-0714","authenticated-orcid":false,"given":"Stephanie M.","family":"Bilinovich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Center for Research in Autism, Intellectual, and Other Neurodevelopmental Disabilities, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Center for Research in Autism, Intellectual, and Other Neurodevelopmental Disabilities, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad R.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie L.","family":"Uhl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"VanSickle","sequence":"additional","affiliation":[{"name":"Spectrum Health Medical Genetics, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surender","family":"Rajasekaran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Pediatric Intensive Care Unit, Helen DeVos Children\u2019s Hospital, Grand Rapids, MI 49503, USA"},{"name":"Office of Research, Spectrum Health, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6510-8560","authenticated-orcid":false,"given":"Andr\u00e9 S.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1002\/iub.230","article-title":"Mammalian Polyamine Metabolism and Function","volume":"61","author":"Pegg","year":"2009","journal-title":"IUBMB Life"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14904","DOI":"10.1074\/jbc.R116.731661","article-title":"Functions of Polyamines in Mammals","volume":"291","author":"Pegg","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9735","DOI":"10.1158\/0008-5472.CAN-07-6866","article-title":"ODC1 Is a Critical Determinant of MYCN Oncogenesis and a Therapeutic Target in Neuroblastoma","volume":"68","author":"Hogarty","year":"2008","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bello-Fernandez, C., and Cleveland, J.L. (1992). C-Myc Transactivates the Ornithine Decarboxylase Gene. Mechanisms in B-Cell Neoplasia 1992, Springer.","DOI":"10.1007\/978-3-642-77633-5_56"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18757","DOI":"10.1074\/jbc.TM118.003336","article-title":"Polyamine Synthesis as a Target of MYC Oncogenes","volume":"293","author":"Bachmann","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1158\/1078-0432.CCR-09-0592","article-title":"Associations of a Polymorphism in the Ornithine Decarboxylase Gene with Colorectal Cancer Survival","volume":"15","author":"Zell","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7859","DOI":"10.1073\/pnas.1332465100","article-title":"Pronounced Reduction in Adenoma Recurrence Associated with Aspirin Use and a Polymorphism in the Ornithine Decarboxylase Gene","volume":"100","author":"Martinez","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s10120-014-0396-5","article-title":"Gene Polymorphisms in the Ornithine Decarboxylase-Polyamine Pathway Modify Gastric Cancer Risk by Interaction with Isoflavone Concentrations","volume":"18","author":"Cho","year":"2015","journal-title":"Gastric Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10689-009-9237-9","article-title":"Genetic Polymorphism in Ornithine Decarboxylase and Risk of Breast Cancer","volume":"8","author":"Brown","year":"2009","journal-title":"Fam. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1097\/01.ju.0000108384.74718.73","article-title":"Association among an Ornithine Decarboxylase Polymorphism, Androgen Receptor Gene (CAG) Repeat Length and Prostate Cancer Risk","volume":"171","author":"Visvanathan","year":"2004","journal-title":"J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nrd2243","article-title":"Targeting Polyamine Metabolism and Function in Cancer and Other Hyperproliferative Diseases","volume":"6","author":"Casero","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5606","DOI":"10.1038\/sj.onc.1208808","article-title":"Key Role for P27Kip1, Retinoblastoma Protein Rb, and MYCN in Polyamine Inhibitor-Induced G1 Cell Cycle Arrest in MYCN-Amplified Human Neuroblastoma Cells","volume":"24","author":"Wallick","year":"2005","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/1940-6207.CAPR-08-0042","article-title":"Difluoromethylornithine plus Sulindac for the Prevention of Sporadic Colorectal Adenomas: A Randomized Placebo-Controlled, Double-Blind Trial","volume":"1","author":"Meyskens","year":"2008","journal-title":"Cancer Prev. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sholler, G.L.S., Gerner, E.W., Bergendahl, G., MacArthur, R.B., VanderWerff, A., Ashikaga, T., Bond, J.P., Ferguson, W., Roberts, W., and Wada, R.K. (2015). A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed\/Refractory Neuroblastoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127246"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.1002\/ijc.33044","article-title":"A Subset Analysis of a Phase II Trial Evaluating the Use of DFMO as Maintenance Therapy for High-Risk Neuroblastoma","volume":"147","author":"Lewis","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1365-4632.2006.01231.x","article-title":"Alpha-Difluoromethylornithine, a Polyamine Inhibitor: Its Potential Role in Controlling Hair Growth and in Cancer Treatment and Chemo-Prevention","volume":"45","author":"Smith","year":"2006","journal-title":"Int. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jaad.2004.08.005","article-title":"Association of a Polymorphism in the Ornithine Decarboxylase Gene with Male Androgenetic Alopecia","volume":"52","author":"Garton","year":"2005","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/ng.3901","article-title":"Disease Model Discovery from 3,328 Gene Knockouts by The International Mouse Phenotyping Consortium","volume":"49","author":"Meehan","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D1056","DOI":"10.1093\/nar\/gky1133","article-title":"Open Targets Platform: New Developments and Updates Two Years On","volume":"47","author":"Pierleoni","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.aninu.2016.12.002","article-title":"Exploring Polyamines: Functions in Embryo\/Fetal Development","volume":"3","author":"Hussain","year":"2017","journal-title":"Anim. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/35056508","article-title":"Regulation of Cellular Polyamines by Antizyme","volume":"2","author":"Coffino","year":"2001","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/jcp.1041070206","article-title":"Cellular Control of Ornithine Decarboxylase Activity by Its Antizyme","volume":"107","author":"Heller","year":"1981","journal-title":"J. Cell Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.1073\/pnas.91.9.3959","article-title":"Polyamines Regulate the Expression of Ornithine Decarboxylase Antizyme in Vitro by Inducing Ribosomal Frame-Shifting","volume":"91","author":"Rom","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8930","DOI":"10.1073\/pnas.91.19.8930","article-title":"Antizyme Protects against Abnormal Accumulation and Toxicity of Polyamines in Ornithine Decarboxylase-Overproducing Cells","volume":"91","author":"Suzuki","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0968-0004(06)80024-1","article-title":"Ornithine Decarboxylase Antizyme: A Novel Type of Regulatory","volume":"21","author":"Hayashi","year":"1996","journal-title":"Protein Trends Biochem. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1042\/bj2040647","article-title":"A Macromolecular Inhibitor of the Antizyme to Ornithine Decarboxylase","volume":"204","author":"Fujita","year":"1982","journal-title":"Biochem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.1074\/jbc.271.7.3340","article-title":"Cloning of Antizyme Inhibitor, a Highly Homologous Protein to Ornithine Decarboxylase","volume":"271","author":"Murakami","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.neuroscience.2007.01.062","article-title":"Putrescine as an Important Source of GABA in the Postnatal Rat Subventricular Zone","volume":"146","author":"Sequerra","year":"2007","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/j.1460-9568.1993.tb00978.x","article-title":"Elevated Seizure Threshold and Impaired Spatial Learning in Transgenic Mice with Putrescine Overproduction in the Brain","volume":"5","author":"Halonen","year":"1993","journal-title":"Eur. J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ajhg.2018.12.017","article-title":"Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder","volume":"104","author":"Ganapathi","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1002\/ajmg.a.40523","article-title":"Novel de Novo Pathogenic Variant in the ODC1 Gene in a Girl with Developmental Delay, Alopecia, and Dysmorphic Features","volume":"176","author":"Bupp","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1002\/ajmg.a.60677","article-title":"Gain-of-Function Variants in the ODC1 Gene Cause a Syndromic Neurodevelopmental Disorder Associated with Macrocephaly, Alopecia, Dysmorphic Features, and Neuroimaging Abnormalities","volume":"176","author":"Rodan","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1042\/BCJ20190294","article-title":"Biochemical Features of Primary Cells from a Pediatric Patient with a Gain-of-Function ODC1 Genetic Mutation","volume":"476","author":"Schultz","year":"2019","journal-title":"Biochem. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/nprot.2013.084","article-title":"De Novo Transcript Sequence Reconstruction from RNA-Seq Using the Trinity Platform for Reference Generation and Analysis","volume":"8","author":"Haas","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X Version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00894-017-3258-3","article-title":"Molecular Modeling in the Age of Clinical Genomics, the Enterprise of the next Generation","volume":"23","author":"Prokop","year":"2017","journal-title":"J. Mol. Model."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Landrum, M.J., Lee, J.M., Riley, G.R., Jang, W., Rubinstein, W.S., Church, D.M., and Maglott, D.R. (2014). ClinVar: Public Archive of Relationships among Sequence Variation and Human Phenotype. Nucl. Acids Res., D980\u2013D985.","DOI":"10.1093\/nar\/gkt1113"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The Mutational Constraint Spectrum Quantified from Variation in 141,456 Humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D945","DOI":"10.1093\/nar\/gkq929","article-title":"COSMIC: Mining Complete Cancer Genomes in the Catalogue of Somatic Mutations in Cancer","volume":"39","author":"Forbes","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/prot.10104","article-title":"Increasing the Precision of Comparative Models with YASARA NOVA--a Self-Parameterizing Force Field","volume":"47","author":"Krieger","year":"2002","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/jcc.10349","article-title":"A Point-Charge Force Field for Molecular Mechanics Simulations of Proteins Based on Condensed-Phase Quantum Mechanical Calculations","volume":"24","author":"Duan","year":"2003","journal-title":"J. Comput. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W529","DOI":"10.1093\/nar\/gkq399","article-title":"ConSurf 2010: Calculating Evolutionary Conservation in Sequence and Structure of Proteins and Nucleic Acids","volume":"38","author":"Ashkenazy","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"GTEx Consortium, Laboratory, Data Analysis &Coordinating Center (LDACC)\u2014Analysis Working Group, Statistical Methods groups\u2014Analysis Working Group, Enhancing GTEx (eGTEx) Groups, NIH Common Fund, NIH\/NCI, NIH\/NHGRI, NIH\/NIMH, NIH\/NIDA, and Biospecimen Collection Source Site\u2014NDRI (2017). Genetic Effects on Gene Expression across Human Tissues. Nature, 550, 204\u2013213.","DOI":"10.1038\/nature24277"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/nbt1210-1248","article-title":"Towards a Knowledge-Based Human Protein Atlas","volume":"28","author":"Uhlen","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Franz\u00e9n, O., Gan, L.-M., and Bj\u00f6rkegren, J.L.M. (2019). PanglaoDB: A Web Server for Exploration of Mouse and Human Single-Cell RNA Sequencing Data. Database.","DOI":"10.1093\/database\/baz046"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tabula Muris Consortium, Overall coordination, Logistical coordination, Organ collection and processing, Library preparation and sequencing, Computational data analysis, Cell type annotation, Writing group, Supplemental text writing group, and Principal investigators (2018). Single-Cell Transcriptomics of 20 Mouse Organs Creates a Tabula Muris. Nature, 562, 367\u2013372.","DOI":"10.1038\/s41586-018-0590-4"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D996","DOI":"10.1093\/nar\/gks1042","article-title":"Allen Brain Atlas: An Integrated Spatio-Temporal Portal for Exploring the Central Nervous System","volume":"41","author":"Sunkin","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D808","DOI":"10.1093\/nar\/gks1094","article-title":"STRING v9.1: Protein-Protein Interaction Networks, with Increased Coverage and Integration","volume":"41","author":"Franceschini","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D552","DOI":"10.1093\/nar\/gkh029","article-title":"GenePaint.Org: An Atlas of Gene Expression Patterns in the Mouse Embryo","volume":"32","author":"Visel","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"W185","DOI":"10.1093\/nar\/gkaa420","article-title":"SNPnexus: A Web Server for Functional Annotation of Human Genome Sequence Variation (2020 Update)","volume":"48","author":"Oscanoa","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fishilevich, S., Nudel, R., Rappaport, N., Hadar, R., Plaschkes, I., Stein, T.I., Rosen, N., Kohn, A., Twik, M., and Safran, M. (2017). GeneHancer: Genome-Wide Integration of Enhancers and Target Genes in GeneCards. Database.","DOI":"10.1093\/database\/bax028"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1101\/gr.137323.112","article-title":"Annotation of Functional Variation in Personal Genomes Using RegulomeDB","volume":"22","author":"Boyle","year":"2012","journal-title":"Genome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D139","DOI":"10.1093\/nar\/gkw1064","article-title":"SNP2TFBS\u2013a Database of Regulatory SNPs Affecting Predicted Transcription Factor Binding Site Affinity","volume":"45","author":"Kumar","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_54","unstructured":"Bilinovich, S.M., Uhl, K.L., Lewis, K., Soehnlen, X., Williams, M., Vogt, D., Prokop, J.W., and Campbell, D.B. (2021). Integrated RNA Sequencing Reveals Epigenetic Impacts of Diesel Particulate Matter Exposure in Human Cerebral Organoids. Dev. Neurosci., 1\u201313."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13059-019-1670-y","article-title":"Alevin Efficiently Estimates Accurate Gene Abundances from DscRNA-Seq Data","volume":"20","author":"Srivastava","year":"2019","journal-title":"Genome Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1093\/emboj\/18.5.1214","article-title":"Translocation of Ornithine Decarboxylase to the Surface Membrane during Cell Activation and Transformation","volume":"18","author":"Heiskala","year":"1999","journal-title":"EMBO J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20959","DOI":"10.1074\/jbc.M314043200","article-title":"Proteasomes Begin Ornithine Decarboxylase Digestion at the C Terminus","volume":"279","author":"Zhang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1159\/000082134","article-title":"SOX2, a Persistent Marker for Multipotential Neural Stem Cells Derived from Embryonic Stem Cells, the Embryo or the Adult","volume":"26","author":"Ellis","year":"2004","journal-title":"Dev. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/360355a0","article-title":"Ornithine Decarboxylase Activity Is Critical for Cell Transformation","volume":"360","author":"Auvinen","year":"1992","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00726-013-1572-3","article-title":"Inflammation, Carcinogenesis and Neurodegeneration Studies in Transgenic Animal Models for Polyamine Research","volume":"46","author":"Cervelli","year":"2014","journal-title":"Amino Acids"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.tig.2008.07.005","article-title":"Oncogenes on My Mind: ERK and MTOR Signaling in Cognitive Diseases","volume":"24","author":"Krab","year":"2008","journal-title":"Trends Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/299640a0","article-title":"Differential Expression of Cellular Oncogenes during Pre- and Postnatal Development of the Mouse","volume":"299","author":"Slamon","year":"1982","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1046\/j.1471-4159.1998.71010288.x","article-title":"Ornithine Decarboxylase in Human Brain: Influence of Aging, Regional Distribution, and Alzheimer\u2019s Disease","volume":"71","author":"Morrison","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_65","first-page":"102","article-title":"Implication of the Polyamine System in Mental Disorders","volume":"33","author":"Fiori","year":"2008","journal-title":"J. Psychiatry. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1097\/00004647-200108000-00007","article-title":"Ornithine Decarboxylase Knockdown Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain","volume":"21","author":"Dogan","year":"2001","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1469-7610.2004.00349.x","article-title":"Foetal Testosterone, Social Relationships, and Restricted Interests in Children","volume":"46","author":"Knickmeyer","year":"2005","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1115455","article-title":"Sex Differences in the Brain: Implications for Explaining Autism","volume":"310","author":"Knickmeyer","year":"2005","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0167-4889(97)00011-6","article-title":"Catecholamines Are Required for Androgen-Induced ODC Expression but Not for Hypertrophy of Mouse Kidney","volume":"1356","author":"Peska","year":"1997","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1042\/BST0350386","article-title":"Nuclear and Membrane Receptor-Mediated Signalling Pathways Modulate Polyamine Biosynthesis and Interconversion","volume":"35","author":"Dudkowska","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1152\/physiolgenomics.00175.2005","article-title":"A Cross-Species Analysis of the Rodent Uterotrophic Program: Elucidation of Conserved Responses and Targets of Estrogen Signaling","volume":"23","author":"Kwekel","year":"2005","journal-title":"Physiol. Genom."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Prokop, J.W., Yeo, N.C., Ottmann, C., Chhetri, S.B., Florus, K.L., Ross, E.J., Sosonkina, N., Link, B.A., Freedman, B.I., and Coppola, C.J. (2018). Characterization of Coding\/Noncoding Variants ForSHROOM3in Patients with CKD. J. Am. Soc. Nephrol.","DOI":"10.1681\/ASN.2017080856"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/4\/470\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:41:03Z","timestamp":1760161263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/4\/470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":72,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["genes12040470"],"URL":"https:\/\/doi.org\/10.3390\/genes12040470","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]}}}