{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:25:48Z","timestamp":1764577548916,"version":"3.46.0"},"reference-count":52,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["SCOPES IZ73Z0_152347\/1"],"award-info":[{"award-number":["SCOPES IZ73Z0_152347\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004742","name":"National Academy of Sciences of Ukraine","doi-asserted-by":"publisher","award":["0121U110054"],"award-info":[{"award-number":["0121U110054"]}],"id":[{"id":"10.13039\/501100004742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["1290589"],"award-info":[{"award-number":["1290589"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>46,XY gonadal dysgenesis, characterised by absent or defective testicular development in individuals with a 46,XY karyotype, results from disruptions in the genetic programme governing testis determination and differentiation during embryogenesis. While monogenic causes explain approximately 50% of cases, emerging evidence suggests an oligogenic basis in some patients. However, many cases remain without a definitive molecular diagnosis. In this study, we investigated a patient with 46,XY gonadal dysgenesis to explore the underlying genetic aetiology. Whole-exome sequencing in the patient did not reveal any pathogenic variants in genes previously associated with this condition. Instead, it detected rare variants in STARD9 and CDK5RAP2, which encode centrosomal proteins known to interact with each other. Gene expression analysis of embryonic gonads revealed that STARD9 is sexually dimorphic, with the highest expression in testis-specific Sertoli cells, while CDK5RAP2 is ubiquitously expressed, including in Sertoli cells. These findings suggest a role for both genes in Sertoli cell development, implicating them in the pathogenesis of 46,XY gonadal dysgenesis. To evaluate the functional relevance of the identified variants, we performed molecular dynamics simulations, which suggest that these variants may impair the individual and\/or combined functions of STARD9 and CDK5RAP2 proteins. This study is the first to propose a role for STARD9 and CDK5RAP2 genes in human Sertoli cell development and highlights their potential contribution to 46,XY gonadal dysgenesis.<\/jats:p>","DOI":"10.3390\/ijms262311575","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"11575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["STARD9 and CDK5RAP2\u2014Novel Candidate Genes for 46,XY Complete Gonadal Dysgenesis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-9120","authenticated-orcid":false,"given":"Dmytro","family":"Sirokha","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7596-6294","authenticated-orcid":false,"given":"Alexey","family":"Rayevsky","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03143 Kyiv, Ukraine"},{"name":"Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine, 04123 Kyiv, Ukraine"},{"name":"Department of Molecular Modeling, Enamine Ltd., 02094 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-3567","authenticated-orcid":false,"given":"Vitalii","family":"Kalynovskyi","sequence":"additional","affiliation":[{"name":"Educational and Scientific Centre \u201cInstitute of Biology and Medicine\u201d, Taras Shevchenko National University of Kyiv, 03022 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4632-5447","authenticated-orcid":false,"given":"Mykola","family":"Khalangot","sequence":"additional","affiliation":[{"name":"Endocrine Department, Shupyk National Healthcare University of Ukraine, 04112 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8449-4279","authenticated-orcid":false,"given":"Oksana","family":"Samson","sequence":"additional","affiliation":[{"name":"Endocrine Department, Shupyk National Healthcare University of Ukraine, 04112 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-8804","authenticated-orcid":false,"given":"Olexandra","family":"Gorodna","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1782-4749","authenticated-orcid":false,"given":"Krystyna","family":"Kwiatkowska","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 61-479 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-4886","authenticated-orcid":false,"given":"Chloe","family":"Mayere","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1733-0589","authenticated-orcid":false,"given":"Zaneta","family":"Lemanska","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 61-479 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6708-6482","authenticated-orcid":false,"given":"Amanda","family":"Kunik","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 61-479 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5462-0676","authenticated-orcid":false,"given":"Serge","family":"Nef","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva Medical School, 1206 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-1193","authenticated-orcid":false,"given":"Kamila","family":"Kusz-Zamelczyk","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 61-479 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-3964","authenticated-orcid":false,"given":"Ludmila","family":"Livshits","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03143 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41574-018-0010-8","article-title":"Caring for individuals with a difference of sex development (DSD): A Consensus Statement","volume":"14","author":"Cools","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101633","DOI":"10.1016\/j.beem.2022.101633","article-title":"Genetics of 46,XY gonadal dysgenesis","volume":"36","author":"Elzaiat","year":"2022","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000521381","article-title":"Monogenic Forms of DSD: An Update","volume":"96","author":"McElreavey","year":"2023","journal-title":"Horm. Res. Paediatr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Camats, N., Fluck, C.E., and Audi, L. (2020). Oligogenic Origin of Differences of Sex Development in Humans. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051809"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000519691","article-title":"Oligogenic Causes of Human Differences of Sex Development: Facing the Challenge of Genetic Complexity","volume":"96","author":"Kouri","year":"2023","journal-title":"Horm. Res. Paediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000445983","article-title":"Identification of NR5A1 Mutations and Possible Digenic Inheritance in 46,XY Gonadal Dysgenesis","volume":"10","author":"Mazen","year":"2016","journal-title":"Sex. Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1399-0004.2012.01879.x","article-title":"Targeted massively parallel sequencing provides comprehensive genetic diagnosis for patients with disorders of sex development","volume":"83","author":"Arboleda","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Barseghyan, H., Symon, A., Zadikyan, M., Almalvez, M., Segura, E.E., Eskin, A., Bramble, M.S., Arboleda, V.A., Baxter, R., and Nelson, S.F. (2018). Identification of novel candidate genes for 46,XY disorders of sex development (DSD) using a C57BL\/6J-YPOS mouse model. Biol. Sex Differ., 9.","DOI":"10.1186\/s13293-018-0167-9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E333","DOI":"10.1210\/jc.2014-2605","article-title":"Exome sequencing for the diagnosis of 46,XY disorders of sex development","volume":"100","author":"Baxter","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Eggers, S., Sadedin, S., van den Bergen, J.A., Robevska, G., Ohnesorg, T., Hewitt, J., Lambeth, L., Bouty, A., Knarston, I.M., and Tan, T.Y. (2016). Disorders of sex development: Insights from targeted gene sequencing of a large international patient cohort. Genome Biol., 17.","DOI":"10.1186\/s13059-016-1105-y"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/adc.2006.098319","article-title":"Consensus statement on management of intersex disorders","volume":"91","author":"Hughes","year":"2006","journal-title":"Arch. Dis. Child."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1159\/000489692","article-title":"A Case of Two Sisters Suffering from 46,XY Gonadal Dysgenesis and Carrying a Mutation of a Novel Candidate Sex-Determining Gene STARD8 on the X Chromosome","volume":"12","author":"Ilaslan","year":"2018","journal-title":"Sex. Dev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ilaslan, E., Markosyan, R., Sproll, P., Stevenson, B.J., Sajek, M., Sajek, M.P., Hayrapetyan, H., Sarkisian, T., Livshits, L., and Nef, S. (2020). The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218403"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1042\/CS20150579","article-title":"Molecular mechanisms associated with 46,XX disorders of sex development","volume":"130","author":"Knarston","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1159\/000537877","article-title":"Mutations in STARD8 (DLC3) May Cause 46,XY Gonadal Dysgenesis","volume":"17","author":"Sirokha","year":"2023","journal-title":"Sex. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.bpobgyn.2017.11.005","article-title":"Disorders of sex development","volume":"48","author":"Witchel","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1038\/s41467-023-39040-0","article-title":"Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects","volume":"14","author":"Ayers","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e82343","DOI":"10.7554\/eLife.82343","article-title":"A conserved function of Human DLC3 and Drosophila Cv-c in testis development","volume":"11","author":"Sotillos","year":"2022","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e70188","DOI":"10.1096\/fj.202401541R","article-title":"Roles of Cep215\/Cdk5rap2 in establishing testicular architecture for mouse male germ cell development","volume":"38","author":"Kang","year":"2024","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.devcel.2010.05.017","article-title":"CDK5RAP2 regulates centriole engagement and cohesion in mice","volume":"18","author":"Barrera","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.cell.2011.11.020","article-title":"The STARD9\/Kif16a kinesin associates with mitotic microtubules and regulates spindle pole assembly","volume":"147","author":"Torres","year":"2011","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.cell.2005.08.029","article-title":"A human protein-protein interaction network: A resource for annotating the proteome","volume":"122","author":"Stelzl","year":"2005","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Arai, M., Suetaka, S., and Ooka, K. (2024). Dynamics and interactions of intrinsically disordered proteins. Curr. Opin. Struct. Biol., 84.","DOI":"10.1016\/j.sbi.2023.102734"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chakrabarti, P., and Chakravarty, D. (2022). Intrinsically disordered proteins\/regions and insight into their biomolecular interactions. Biophys. Chem., 283.","DOI":"10.1016\/j.bpc.2022.106769"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41586-022-04918-4","article-title":"Single-cell roadmap of human gonadal development","volume":"607","author":"Lorenzi","year":"2022","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eabm0972","DOI":"10.1126\/sciadv.abm0972","article-title":"Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad","volume":"8","author":"Mayere","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_27","first-page":"170","article-title":"Potential Effect of Post-Transcriptional Substitutions of Tyrosine for Cysteine Residues on Transformation of Amyloidogenic Proteins","volume":"87","author":"Muronetz","year":"2022","journal-title":"Biochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10128","DOI":"10.1074\/jbc.M307563200","article-title":"Tyrosine-to-cysteine modification of human alpha-synuclein enhances protein aggregation and cellular toxicity","volume":"279","author":"Zhou","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1080\/15384101.2018.1513764","article-title":"A centrosomal protein STARD9 promotes microtubule stability and regulates spindle microtubule dynamics","volume":"17","author":"Srivastava","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1016\/j.devcel.2024.09.001","article-title":"CDK5RAP2 activates microtubule nucleator gammaTuRC by facilitating template formation and actin release","volume":"59","author":"Serna","year":"2024","journal-title":"Dev. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1002\/ajmg.a.38391","article-title":"A novel genetic syndrome with STARD9 mutation and abnormal spindle morphology","volume":"173","author":"Okamoto","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1017\/S0016672318000046","article-title":"Comprehensive review on the molecular genetics of autosomal recessive primary microcephaly (MCPH)","volume":"100","author":"Naveed","year":"2018","journal-title":"Genet. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.tjog.2023.03.015","article-title":"A novel missense variant in CDK5RAP2 associated with non-obstructive azoospermia","volume":"62","author":"Rahimian","year":"2023","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"770782","DOI":"10.3389\/fendo.2021.770782","article-title":"Disorders of Sex Development of Adrenal Origin","volume":"12","author":"Finkielstain","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6573","DOI":"10.1021\/bi012159+","article-title":"Intrinsic disorder and protein function","volume":"41","author":"Dunker","year":"2002","journal-title":"Biochemistry"},{"key":"ref_36","first-page":"rs1","article-title":"Proteome-wide discovery of evolutionary conserved sequences in disordered regions","volume":"5","author":"Yeh","year":"2012","journal-title":"Sci. Signal"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S1093-3263(00)00138-8","article-title":"Intrinsically disordered protein","volume":"19","author":"Dunker","year":"2001","journal-title":"J. Mol. Graph. Model."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1006\/jmbi.1994.1545","article-title":"Helix-stabilizing interaction between tyrosine and leucine or valine when the spacing is i,i + 4","volume":"241","author":"Padmanabhan","year":"1994","journal-title":"J. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1021\/ar300087y","article-title":"Aromatic-proline interactions: Electronically tunable CH\/pi interactions","volume":"46","author":"Zondlo","year":"2013","journal-title":"Acc. Chem. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.bpj.2017.02.029","article-title":"The Role of Evolutionary Selection in the Dynamics of Protein Structure Evolution","volume":"112","author":"Gilson","year":"2017","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1093\/bioinformatics\/bti537","article-title":"FoldIndex: A simple tool to predict whether a given protein sequence is intrinsically unfolded","volume":"21","author":"Prilusky","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1093\/nar\/gkg515","article-title":"NORSp: Predictions of long regions without regular secondary structure","volume":"31","author":"Liu","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1093\/nar\/gkg519","article-title":"GlobPlot: Exploring protein sequences for globularity and disorder","volume":"31","author":"Linding","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcc.23354","article-title":"CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data","volume":"34","author":"Huang","year":"2013","journal-title":"J. Comput. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"W297","DOI":"10.1093\/nar\/gkab408","article-title":"IUPred3: Prediction of protein disorder enhanced with unambiguous experimental annotation and visualization of evolutionary conservation","volume":"49","author":"Erdos","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1093\/bioinformatics\/btm349","article-title":"Natively unstructured regions in proteins identified from contact predictions","volume":"23","author":"Schlessinger","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1093\/bioinformatics\/btl504","article-title":"FoldUnfold: Web server for the prediction of disordered regions in protein chain","volume":"22","author":"Galzitskaya","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1021\/acs.jctc.9b00006","article-title":"The SIRAH 2.0 Force Field: Altius, Fortius, Citius","volume":"15","author":"Machado","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1021\/acs.jcim.3c01344","article-title":"DSSP in GROMACS: Tool for Defining Secondary Structures of Proteins in Trajectories","volume":"64","author":"Gorelov","year":"2024","journal-title":"J. Chem. Inf. Model."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1471-2105-15-S17-S4","article-title":"Improving protein order-disorder classification using charge-hydropathy plots","volume":"15","author":"Huang","year":"2014","journal-title":"BMC Bioinform."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11575\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:23:40Z","timestamp":1764577420000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":52,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311575"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311575","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]}}}