{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T18:47:53Z","timestamp":1778611673217,"version":"3.51.4"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82071462"],"award-info":[{"award-number":["82071462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004761","name":"the Natural Science Foundation of Hunan Province","doi-asserted-by":"crossref","award":["2022SK2026"],"award-info":[{"award-number":["2022SK2026"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-92027-3","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T14:37:06Z","timestamp":1741012626000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The phenotypic and genetic spectrum of AKT3-related neurodevelopmental condition"],"prefix":"10.1038","volume":"15","author":[{"given":"Xiaole","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-6962","authenticated-orcid":false,"given":"Jing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"92027_CR1","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","volume":"28","author":"K Sun","year":"2020","unstructured":"Sun, K. et al. The PI3K\/AKT\/mTOR signaling pathway in osteoarthritis: a narrative review. Osteoarthritis Cartilage 28, 400\u2013409. https:\/\/doi.org\/10.1016\/j.joca.2020.02.027 (2020).","journal-title":"Osteoarthritis Cartilage"},{"key":"92027_CR2","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.ctrv.2014.03.004","volume":"40","author":"EM Ciruelos Gil","year":"2014","unstructured":"Ciruelos Gil, E. M. Targeting the PI3K\/AKT\/mTOR pathway in estrogen receptor-positive breast cancer. Cancer Treat Rev. 40, 862\u2013871. https:\/\/doi.org\/10.1016\/j.ctrv.2014.03.004 (2014).","journal-title":"Cancer Treat Rev."},{"key":"92027_CR3","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.1093\/brain\/awx203","volume":"140","author":"D Alcantara","year":"2017","unstructured":"Alcantara, D. et al. Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly. Brain 140, 2610\u20132622. https:\/\/doi.org\/10.1093\/brain\/awx203 (2017).","journal-title":"Brain"},{"key":"92027_CR4","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1093\/brain\/awab376","volume":"145","author":"F Pirozzi","year":"2022","unstructured":"Pirozzi, F. et al. Profiling PI3K-AKT-MTOR variants in focal brain malformations reveals new insights for diagnostic care. Brain 145, 925\u2013938. https:\/\/doi.org\/10.1093\/brain\/awab376 (2022).","journal-title":"Brain"},{"key":"92027_CR5","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/uog.23715","volume":"59","author":"N Bourgon","year":"2022","unstructured":"Bourgon, N. et al. Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K-AKT-mTOR signaling pathway. Ultrasound. Obstet. Gynecol. 59, 532\u2013542. https:\/\/doi.org\/10.1002\/uog.23715 (2022).","journal-title":"Ultrasound. Obstet. Gynecol."},{"key":"92027_CR6","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1002\/ajmg.c.31736","volume":"181","author":"WB Dobyns","year":"2019","unstructured":"Dobyns, W. B. & Mirzaa, G. M. Megalencephaly syndromes associated with mutations of core components of the PI3K-AKT-MTOR pathway: PIK3CA, PIK3R2, AKT3, and MTOR. Am. J. Med. Genet. C Semin. Med. Genet. 181, 582\u2013590. https:\/\/doi.org\/10.1002\/ajmg.c.31736 (2019).","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"92027_CR7","doi-asserted-by":"publisher","first-page":"4215","DOI":"10.1182\/blood-2010-12-323204","volume":"118","author":"KA O'Brien","year":"2011","unstructured":"O\u2019Brien, K. A., Stojanovic-Terpo, A., Hay, N. & Du, X. An important role for Akt3 in platelet activation and thrombosis. Blood 118, 4215\u20134223. https:\/\/doi.org\/10.1182\/blood-2010-12-323204 (2011).","journal-title":"Blood"},{"key":"92027_CR8","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/s0955-0674(98)80149-x","volume":"10","author":"J Downward","year":"1998","unstructured":"Downward, J. Mechanisms and consequences of activation of protein kinase B\/Akt. Curr. Opin. Cell Biol. 10, 262\u2013267. https:\/\/doi.org\/10.1016\/s0955-0674(98)80149-x (1998).","journal-title":"Curr. Opin. Cell Biol."},{"key":"92027_CR9","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1074\/mcp.M113.035600","volume":"13","author":"L Fagerberg","year":"2014","unstructured":"Fagerberg, L. et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol. Cell Proteomics 13, 397\u2013406. https:\/\/doi.org\/10.1074\/mcp.M113.035600 (2014).","journal-title":"Mol. Cell Proteomics"},{"key":"92027_CR10","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1128\/MCB.25.5.1869-1878.2005","volume":"25","author":"RM Easton","year":"2005","unstructured":"Easton, R. M. et al. Role for Akt3\/protein kinase Bgamma in attainment of normal brain size. Mol. Cell Biol. 25, 1869\u20131878. https:\/\/doi.org\/10.1128\/MCB.25.5.1869-1878.2005 (2005).","journal-title":"Mol. Cell Biol."},{"key":"92027_CR11","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.1242\/dev.01864","volume":"132","author":"O Tschopp","year":"2005","unstructured":"Tschopp, O. et al. Essential role of protein kinase B gamma (PKB gamma\/Akt3) in postnatal brain development but not in glucose homeostasis. Development 132, 2943\u20132954. https:\/\/doi.org\/10.1242\/dev.01864 (2005).","journal-title":"Development"},{"key":"92027_CR12","unstructured":"Mirzaa, G. in GeneReviews((R)) (eds M. P. Adam et al.) (1993)."},{"key":"92027_CR13","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.23188","author":"M Luca","year":"2023","unstructured":"Luca, M. et al. The somatic p. T81dup variant in AKT3 gene underlies a mild cerebral phenotype and expands the spectrum including capillary malformation and lateralized overgrowth. Genes Chromosomes Cancer https:\/\/doi.org\/10.1002\/gcc.23188 (2023).","journal-title":"Genes Chromosomes Cancer"},{"key":"92027_CR14","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000006521","author":"B Aleksiuniene","year":"2017","unstructured":"Aleksiuniene, B. et al. Opposite chromosome constitutions due to a familial translocation t(1;21)(q43;q22) in 2 cousins with development delay and congenital anomalies: A case report. Medicine (Baltimore) https:\/\/doi.org\/10.1097\/MD.0000000000006521 (2017).","journal-title":"Medicine (Baltimore)"},{"key":"92027_CR15","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3389\/fgene.2019.00058","volume":"10","author":"F Lopes","year":"2019","unstructured":"Lopes, F. et al. The Role of AKT3 Copy number changes in brain abnormalities and neurodevelopmental disorders: four new cases and literature review. Front. Genet. 10, 58. https:\/\/doi.org\/10.3389\/fgene.2019.00058 (2019).","journal-title":"Front. Genet."},{"key":"92027_CR16","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1086\/519999","volume":"81","author":"E Boland","year":"2007","unstructured":"Boland, E. et al. Mapping of deletion and translocation breakpoints in 1q44 implicates the serine\/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum. Am. J. Hum. Genet. 81, 292\u2013303. https:\/\/doi.org\/10.1086\/519999 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"92027_CR17","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13039-022-00620-2","volume":"15","author":"B Khadija","year":"2022","unstructured":"Khadija, B. et al. Clinical and molecular characterization of 1q43q44 deletion and corpus callosum malformations: 2 new cases and literature review. Mol. Cytogenet. 15, 42. https:\/\/doi.org\/10.1186\/s13039-022-00620-2 (2022).","journal-title":"Mol. Cytogenet."},{"key":"92027_CR18","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/ng.2331","volume":"44","author":"JB Riviere","year":"2012","unstructured":"Riviere, J. B. et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat. Genet. 44, 934\u2013940. https:\/\/doi.org\/10.1038\/ng.2331 (2012).","journal-title":"Nat. Genet."},{"key":"92027_CR19","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/ng.2329","volume":"44","author":"JH Lee","year":"2012","unstructured":"Lee, J. H. et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. 44, 941\u2013945. https:\/\/doi.org\/10.1038\/ng.2329 (2012).","journal-title":"Nat. Genet."},{"key":"92027_CR20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.neuron.2012.03.010","volume":"74","author":"A Poduri","year":"2012","unstructured":"Poduri, A. et al. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron 74, 41\u201348. https:\/\/doi.org\/10.1016\/j.neuron.2012.03.010 (2012).","journal-title":"Neuron"},{"key":"92027_CR21","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1056\/NEJMoa1314432","volume":"371","author":"SS Jamuar","year":"2014","unstructured":"Jamuar, S. S. et al. Somatic mutations in cerebral cortical malformations. N. Engl. J. Med. 371, 733\u2013743. https:\/\/doi.org\/10.1056\/NEJMoa1314432 (2014).","journal-title":"N. Engl. J. Med."},{"key":"92027_CR22","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/cge.12188","volume":"85","author":"K Nakamura","year":"2014","unstructured":"Nakamura, K. et al. AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. Clin. Genet. 85, 396\u2013398. https:\/\/doi.org\/10.1111\/cge.12188 (2014).","journal-title":"Clin. Genet."},{"key":"92027_CR23","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s00381-014-2589-y","volume":"31","author":"A Harada","year":"2015","unstructured":"Harada, A. et al. Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3. Childs Nerv. Syst. 31, 465\u2013471. https:\/\/doi.org\/10.1007\/s00381-014-2589-y (2015).","journal-title":"Childs Nerv. Syst."},{"key":"92027_CR24","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1093\/brain\/awv045","volume":"138","author":"LA Jansen","year":"2015","unstructured":"Jansen, L. A. et al. PI3K\/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. Brain 138, 1613\u20131628. https:\/\/doi.org\/10.1093\/brain\/awv045 (2015).","journal-title":"Brain"},{"key":"92027_CR25","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.ymgme.2014.11.018","volume":"114","author":"M Nellist","year":"2015","unstructured":"Nellist, M. et al. Germline activating AKT3 mutation associated with megalencephaly, polymicrogyria, epilepsy and hypoglycemia. Mol. Genet. Metab. 114, 467\u2013473. https:\/\/doi.org\/10.1016\/j.ymgme.2014.11.018 (2015).","journal-title":"Mol. Genet. Metab."},{"key":"92027_CR26","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1002\/ajmg.a.38099","volume":"173","author":"M Takagi","year":"2017","unstructured":"Takagi, M. et al. A novel de novo germline mutation Glu40Lys in AKT3 causes megalencephaly with growth hormone deficiency. Am. J. Med. Genet. A 173, 1071\u20131076. https:\/\/doi.org\/10.1002\/ajmg.a.38099 (2017).","journal-title":"Am. J. Med. Genet. A"},{"key":"92027_CR27","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12881-016-0363-6","volume":"18","author":"Y Negishi","year":"2017","unstructured":"Negishi, Y. et al. A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly. BMC Med. Genet. 18, 4. https:\/\/doi.org\/10.1186\/s12881-016-0363-6 (2017).","journal-title":"BMC Med. Genet."},{"key":"92027_CR28","unstructured":"(!!! INVALID CITATION !!! )."},{"key":"92027_CR29","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1186\/s13023-020-01599-y","volume":"15","author":"L Lin","year":"2020","unstructured":"Lin, L. et al. Clinical and genetic characteristics and prenatal diagnosis of patients presented GDD\/ID with rare monogenic causes. Orphanet. J. Rare Dis. 15, 317. https:\/\/doi.org\/10.1186\/s13023-020-01599-y (2020).","journal-title":"Orphanet. J. Rare Dis."},{"key":"92027_CR30","doi-asserted-by":"publisher","first-page":"e16132","DOI":"10.7759\/cureus.16132","volume":"13","author":"JF Ortiz","year":"2021","unstructured":"Ortiz, J. F. et al. Megalencephaly polymicrogyria polydactyly hydrocephalus (MPPH): A case report and review of literature. Cureus 13, e16132. https:\/\/doi.org\/10.7759\/cureus.16132 (2021).","journal-title":"Cureus"},{"key":"92027_CR31","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63585","author":"E Renard","year":"2024","unstructured":"Renard, E. et al. Megalencephaly secondary to a novel germline missense variant p Asp322Tyr in AKT3 associated with growth hormone deficiency and central hypothyroidism: A case report. Am J Med Genet A https:\/\/doi.org\/10.1002\/ajmg.a.63585 (2024).","journal-title":"Am J Med Genet A"},{"key":"92027_CR32","doi-asserted-by":"publisher","first-page":"e63551","DOI":"10.1002\/ajmg.a.63551","volume":"194","author":"M De Bortoli","year":"2024","unstructured":"De Bortoli, M. et al. Epilepsy with faint capillary malformation or reticulated telangiectasia associated with mosaic AKT3 pathogenic variants. Am. J. Med. Genet. A 194, e63551. https:\/\/doi.org\/10.1002\/ajmg.a.63551 (2024).","journal-title":"Am. J. Med. Genet. A"},{"key":"92027_CR33","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad174","author":"R Checri","year":"2023","unstructured":"Checri, R. et al. Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup. Brain Commun. https:\/\/doi.org\/10.1093\/braincomms\/fcad174 (2023).","journal-title":"Brain Commun."},{"key":"92027_CR34","doi-asserted-by":"publisher","first-page":"293","DOI":"10.4103\/aian.aian_92_23","volume":"26","author":"C Gunay","year":"2023","unstructured":"Gunay, C., Kurul, S. H. & Yis, U. Bilateral sensorineural hearing loss in akt3 mutation: a case report and brief review of the literature. Ann. Indian Acad.Neurol. 26, 293\u2013296. https:\/\/doi.org\/10.4103\/aian.aian_92_23 (2023).","journal-title":"Ann. Indian Acad.Neurol."},{"key":"92027_CR35","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.jmoldx.2023.04.003","volume":"25","author":"SH Kim","year":"2023","unstructured":"Kim, S. H. et al. Detecting low-variant allele frequency mosaic pathogenic variants of NF1, TSC2, and AKT3 genes from blood in patients with neurodevelopmental disorders. J. Mol. Diagn. 25, 583\u2013591. https:\/\/doi.org\/10.1016\/j.jmoldx.2023.04.003 (2023).","journal-title":"J. Mol. Diagn."},{"key":"92027_CR36","doi-asserted-by":"publisher","first-page":"e2086","DOI":"10.1002\/mgg3.2086","volume":"10","author":"Y Xu","year":"2022","unstructured":"Xu, Y. et al. Identification of genetic characteristics in pediatric epilepsy with focal cortical dysplasia type 2 using deep whole-exome sequencing. Mol Genet Genomic Med 10, e2086. https:\/\/doi.org\/10.1002\/mgg3.2086 (2022).","journal-title":"Mol Genet Genomic Med"},{"key":"92027_CR37","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.jaad.2021.06.877","volume":"87","author":"OMT Davies","year":"2022","unstructured":"Davies, O. M. T. et al. Cutaneous vascular anomalies associated with a mosaic variant of AKT3: Genetic analysis continues to refine the diagnosis, nomenclature, and classification of vascular anomalies. J. Am. Acad. Dermatol. 87, 162\u2013164. https:\/\/doi.org\/10.1016\/j.jaad.2021.06.877 (2022).","journal-title":"J. Am. Acad. Dermatol."},{"key":"92027_CR38","doi-asserted-by":"publisher","first-page":"104471","DOI":"10.1016\/j.yexmp.2020.104471","volume":"115","author":"R Szalai","year":"2020","unstructured":"Szalai, R. et al. Maternal mosaicism underlies the inheritance of a rare germline AKT3 variant which is responsible for megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome in two Roma half-siblings. Exp. Mol. Pathol. 115, 104471. https:\/\/doi.org\/10.1016\/j.yexmp.2020.104471 (2020).","journal-title":"Exp. Mol. Pathol."},{"key":"92027_CR39","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1007\/s00401-019-02061-5","volume":"138","author":"S Baldassari","year":"2019","unstructured":"Baldassari, S. et al. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta. Neuropathol. 138, 885\u2013900. https:\/\/doi.org\/10.1007\/s00401-019-02061-5 (2019).","journal-title":"Acta. Neuropathol."},{"key":"92027_CR40","doi-asserted-by":"publisher","first-page":"7873","DOI":"10.1007\/s00018-021-03993-6","volume":"78","author":"M Sharma","year":"2021","unstructured":"Sharma, M. & Dey, C. S. Role of Akt isoforms in neuronal insulin signaling and resistance. Cell Mol. Life Sci. 78, 7873\u20137898. https:\/\/doi.org\/10.1007\/s00018-021-03993-6 (2021).","journal-title":"Cell Mol. Life Sci."},{"key":"92027_CR41","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1002\/ajmg.a.35999","volume":"161A","author":"D Wang","year":"2013","unstructured":"Wang, D., Zeesman, S., Tarnopolsky, M. A. & Nowaczyk, M. J. Duplication of AKT3 as a cause of macrocephaly in duplication 1q43q44. Am. J. Med. Genet. A 161A, 2016\u20132019. https:\/\/doi.org\/10.1002\/ajmg.a.35999 (2013).","journal-title":"Am. J. Med. Genet. A"},{"key":"92027_CR42","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1002\/ajmg.a.31776","volume":"143A","author":"AD Hill","year":"2007","unstructured":"Hill, A. D. et al. A 2-Mb critical region implicated in the microcephaly associated with terminal 1q deletion syndrome. Am. J. Med. Genet. A 143A, 1692\u20131698. https:\/\/doi.org\/10.1002\/ajmg.a.31776 (2007).","journal-title":"Am. J. Med. Genet. A"},{"key":"92027_CR43","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1136\/jmg.2007.055830","volume":"45","author":"BW van Bon","year":"2008","unstructured":"van Bon, B. W. et al. Clinical and molecular characteristics of 1qter microdeletion syndrome: delineating a critical region for corpus callosum agenesis\/hypogenesis. J. Med. Genet. 45, 346\u2013354. https:\/\/doi.org\/10.1136\/jmg.2007.055830 (2008).","journal-title":"J. Med. Genet."},{"key":"92027_CR44","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/ejhg.2011.171","volume":"20","author":"SC Nagamani","year":"2012","unstructured":"Nagamani, S. C. et al. Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44. Eur. J. Hum. Genet. 20, 176\u2013179. https:\/\/doi.org\/10.1038\/ejhg.2011.171 (2012).","journal-title":"Eur. J. Hum. Genet."},{"key":"92027_CR45","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00439-017-1772-0","volume":"136","author":"C Depienne","year":"2017","unstructured":"Depienne, C. et al. Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU. Hum. Genet. 136, 463\u2013479. https:\/\/doi.org\/10.1007\/s00439-017-1772-0 (2017).","journal-title":"Hum. Genet."},{"key":"92027_CR46","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13167","author":"T Zhang","year":"2019","unstructured":"Zhang, T. et al. Akt3 deletion in mice impairs spatial cognition and hippocampal CA1 long long-term potentiation through downregulation of mTOR. Acta. Physiol. (Oxf) https:\/\/doi.org\/10.1111\/apha.13167 (2019).","journal-title":"Acta. Physiol. (Oxf)"},{"key":"92027_CR47","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1080\/14728222.2017.1279147","volume":"21","author":"SV Madhunapantula","year":"2017","unstructured":"Madhunapantula, S. V. & Robertson, G. P. Targeting protein kinase-b3 (akt3) signaling in melanoma. Expert Opin. Ther. Targets 21, 273\u2013290. https:\/\/doi.org\/10.1080\/14728222.2017.1279147 (2017).","journal-title":"Expert Opin. Ther. Targets"},{"key":"92027_CR48","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","volume":"22","author":"A Glaviano","year":"2023","unstructured":"Glaviano, A. et al. PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer. Mol. Cancer. 22, 138. https:\/\/doi.org\/10.1186\/s12943-023-01827-6 (2023).","journal-title":"Mol. Cancer."},{"key":"92027_CR49","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/cns.12869","volume":"25","author":"J Peng","year":"2019","unstructured":"Peng, J. et al. Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy. CNS Neurosci. Ther. 25, 14\u201320. https:\/\/doi.org\/10.1111\/cns.12869 (2019).","journal-title":"CNS Neurosci. Ther."},{"key":"92027_CR50","doi-asserted-by":"publisher","first-page":"D1478","DOI":"10.1093\/nar\/gkad1061","volume":"52","author":"Z Wang","year":"2024","unstructured":"Wang, Z. et al. VarCards2: an integrated genetic and clinical database for ACMG-AMP variant-interpretation guidelines in the human whole genome. Nucleic Acids Res. 52, D1478\u2013D1489. https:\/\/doi.org\/10.1093\/nar\/gkad1061 (2024).","journal-title":"Nucleic Acids Res."},{"key":"92027_CR51","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet. Med. 17, 405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30 (2015).","journal-title":"Genet. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92027-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92027-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92027-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T14:37:10Z","timestamp":1741012630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92027-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,3]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["92027"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-92027-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,3]]},"assertion":[{"value":"9 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was approved by the Ethics Committee of Xiangya Hospital of Central South University (Human Study\/Protocol #202310892) and was conducted in accordance with the ethical standards outlines in the Declaration of Helsinki. Written informed consent was obtained from the participants\u2019 legal guardian.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We obtained the written consent for publication from the guardian of the patient.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}}],"article-number":"7484"}}