{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:10:01Z","timestamp":1790716201065,"version":"4.1.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"18","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["FF66\/028"],"award-info":[{"award-number":["FF66\/028"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021186","name":"Office of National Higher Education Science Research and Innovation Policy Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021186","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Heliyon"],"published-print":{"date-parts":[[2024,9]]},"DOI":"10.1016\/j.heliyon.2024.e38020","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T05:22:58Z","timestamp":1726636978000},"page":"e38020","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic modifications of EGLN1 reactivate HbF production in \u03b20-thalassemia\/HbE"],"prefix":"10.1016","volume":"10","author":[{"given":"Varit","family":"Jan-ngam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siriraj","family":"Boontha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Tubsuwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somsakul Pop","family":"Wongpalee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanda","family":"Fanhchaksai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adisak","family":"Tantiworawit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimlak","family":"Charoenkwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-6272","authenticated-orcid":false,"given":"Pinyaphat","family":"Khamphikham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"D1","key":"10.1016\/j.heliyon.2024.e38020_bib1","doi-asserted-by":"crossref","first-page":"D1192","DOI":"10.1093\/nar\/gkaa959","article-title":"Clinically relevant updates of the HbVar database of human hemoglobin variants and thalassemia mutations","volume":"49","author":"Giardine","year":"2021","journal-title":"Nucleic Acids Res."},{"issue":"22","key":"10.1016\/j.heliyon.2024.e38020_bib2","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1182\/blood-2010-01-251348","article-title":"The inherited diseases of hemoglobin are an emerging global health burden","volume":"115","author":"Weatherall","year":"2010","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.heliyon.2024.e38020_bib3","first-page":"522","article-title":"Hb E\/beta-thalassaemia: a common & clinically diverse disorder","volume":"134","author":"Olivieri","year":"2011","journal-title":"Indian J. Med. Res."},{"issue":"8","key":"10.1016\/j.heliyon.2024.e38020_bib4","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a011734","article-title":"The hemoglobin E thalassemias","volume":"2","author":"Fucharoen","year":"2012","journal-title":"Cold Spring Harb Perspect Med."},{"issue":"6","key":"10.1016\/j.heliyon.2024.e38020_bib5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/00043426-200011000-00026","article-title":"Genetic factors affecting clinical severity in beta-thalassemia syndromes","volume":"22","author":"Winichagoon","year":"2000","journal-title":"J. Pediatr. Hematol. Oncol."},{"issue":"5","key":"10.1016\/j.heliyon.2024.e38020_bib6","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1073\/pnas.0711566105","article-title":"Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia","volume":"105","author":"Uda","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"3","key":"10.1016\/j.heliyon.2024.e38020_bib7","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00439-009-0770-2","article-title":"A genome-wide association identified the common genetic variants influence disease severity in beta0-thalassemia\/hemoglobin E","volume":"127","author":"Nuinoon","year":"2010","journal-title":"Hum. Genet."},{"issue":"9","key":"10.1016\/j.heliyon.2024.e38020_bib8","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1056\/NEJMoa1103070","article-title":"A functional element necessary for fetal hemoglobin silencing","volume":"365","author":"Sankaran","year":"2011","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"10.1016\/j.heliyon.2024.e38020_bib9","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1182\/blood-2014-03-561779","article-title":"KLF1 mutations are relatively more common in a thalassemia endemic region and ameliorate the severity of beta-thalassemia","volume":"124","author":"Liu","year":"2014","journal-title":"Blood"},{"issue":"5909","key":"10.1016\/j.heliyon.2024.e38020_bib10","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1126\/science.1165409","article-title":"Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A","volume":"322","author":"Sankaran","year":"2008","journal-title":"Science"},{"issue":"7577","key":"10.1016\/j.heliyon.2024.e38020_bib11","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nature15521","article-title":"BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis","volume":"527","author":"Canver","year":"2015","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.heliyon.2024.e38020_bib12","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2029392","article-title":"Post-transcriptional genetic silencing of BCL11A to treat sickle cell disease","volume":"384","author":"Esrick","year":"2021","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.heliyon.2024.e38020_bib13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 gene editing for sickle cell disease and beta-thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N. Engl. J. Med."},{"issue":"9","key":"10.1016\/j.heliyon.2024.e38020_bib14","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1056\/NEJMoa2215643","article-title":"CRISPR-Cas9 editing of the HBG1 and HBG2 promoters to treat sickle cell disease","volume":"389","author":"Sharma","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.heliyon.2024.e38020_bib15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1182\/blood-2023-179331","article-title":"Targeted degradation of the wiz transcription factor for gamma globin de-repression","volume":"142","author":"Ting","year":"2023","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.heliyon.2024.e38020_bib16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/MOH.0b013e3280de2bf1","article-title":"Molecular insights into stress erythropoiesis","volume":"14","author":"Socolovsky","year":"2007","journal-title":"Curr. Opin. Hematol."},{"issue":"3","key":"10.1016\/j.heliyon.2024.e38020_bib17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/MOH.0b013e32834521c8","article-title":"Stress erythropoiesis: new signals and new stress progenitor cells","volume":"18","author":"Paulson","year":"2011","journal-title":"Curr. Opin. Hematol."},{"key":"10.1016\/j.heliyon.2024.e38020_bib18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.exphem.2020.07.011","article-title":"Stress erythropoiesis: definitions and models for its study","volume":"89","author":"Paulson","year":"2020","journal-title":"Exp. Hematol."},{"issue":"5516","key":"10.1016\/j.heliyon.2024.e38020_bib19","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"issue":"5516","key":"10.1016\/j.heliyon.2024.e38020_bib20","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1059796","article-title":"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation","volume":"292","author":"Jaakkola","year":"2001","journal-title":"Science."},{"issue":"407","key":"10.1016\/j.heliyon.2024.e38020_bib21","doi-asserted-by":"crossref","DOI":"10.1126\/stke.4072007cm8","article-title":"Hypoxia-inducible factor 1 (HIF-1) pathway","volume":"2007","author":"Semenza","year":"2007","journal-title":"Sci. STKE"},{"issue":"4","key":"10.1016\/j.heliyon.2024.e38020_bib22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2008.04.009","article-title":"Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway","volume":"30","author":"Kaelin","year":"2008","journal-title":"Mol. Cell."},{"issue":"6","key":"10.1016\/j.heliyon.2024.e38020_bib23","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1182\/blood-2007-02-073254","article-title":"HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques","volume":"110","author":"Hsieh","year":"2007","journal-title":"Blood"},{"issue":"7933","key":"10.1016\/j.heliyon.2024.e38020_bib24","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/s41586-022-05312-w","article-title":"Activation of gamma-globin expression by hypoxia-inducible factor 1alpha","volume":"610","author":"Feng","year":"2022","journal-title":"Nature"},{"issue":"11","key":"10.1016\/j.heliyon.2024.e38020_bib25","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1182\/bloodadvances.2021006802","article-title":"Identification of novel gamma-globin inducers among all potential erythroid druggable targets","volume":"6","author":"Yu","year":"2022","journal-title":"Blood Adv"},{"issue":"37","key":"10.1016\/j.heliyon.2024.e38020_bib26","doi-asserted-by":"crossref","first-page":"38458","DOI":"10.1074\/jbc.M406026200","article-title":"Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor","volume":"279","author":"Appelhoff","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"4","key":"10.1016\/j.heliyon.2024.e38020_bib27","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/cdd.2008.10","article-title":"Role and regulation of prolyl hydroxylase domain proteins","volume":"15","author":"Fong","year":"2008","journal-title":"Cell Death Differ."},{"issue":"47","key":"10.1016\/j.heliyon.2024.e38020_bib28","doi-asserted-by":"crossref","first-page":"33571","DOI":"10.1074\/jbc.M113.482364","article-title":"A knock-in mouse model of human PHD2 gene-associated erythrocytosis establishes a haploinsufficiency mechanism","volume":"288","author":"Arsenault","year":"2013","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.heliyon.2024.e38020_bib29","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1002\/ajh.21130","article-title":"A scoring system for the classification of beta-thalassemia\/Hb E disease severity","volume":"83","author":"Sripichai","year":"2008","journal-title":"Am. J. Hematol."},{"issue":"4","key":"10.1016\/j.heliyon.2024.e38020_bib30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"issue":"Web Server issue","key":"10.1016\/j.heliyon.2024.e38020_bib31","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT web server: predicting effects of amino acid substitutions on proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res."},{"issue":"16","key":"10.1016\/j.heliyon.2024.e38020_bib32","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels","volume":"31","author":"Choi","year":"2015","journal-title":"Bioinformatics"},{"issue":"5","key":"10.1016\/j.heliyon.2024.e38020_bib33","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41591-019-0401-y","article-title":"Highly efficient therapeutic gene editing of human hematopoietic stem cells","volume":"25","author":"Wu","year":"2019","journal-title":"Nat. Med."},{"issue":"1","key":"10.1016\/j.heliyon.2024.e38020_bib34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1089\/crispr.2021.0113","article-title":"Inference of CRISPR Edits from sanger trace data","volume":"5","author":"Conant","year":"2022","journal-title":"CRISPR J."},{"issue":"4","key":"10.1016\/j.heliyon.2024.e38020_bib35","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/ng1019","article-title":"Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia","volume":"32","author":"Ang","year":"2002","journal-title":"Nat. Genet."},{"issue":"2","key":"10.1016\/j.heliyon.2024.e38020_bib36","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMoa073123","article-title":"A gain-of-function mutation in the HIF2A gene in familial erythrocytosis","volume":"358","author":"Percy","year":"2008","journal-title":"N. Engl. J. Med."},{"issue":"25","key":"10.1016\/j.heliyon.2024.e38020_bib37","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1056\/NEJMoa0806277","article-title":"PHD2 mutation and congenital erythrocytosis with paraganglioma","volume":"359","author":"Ladroue","year":"2008","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.heliyon.2024.e38020_bib38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3324\/haematol.2011.044644","article-title":"Distinct deregulation of the hypoxia inducible factor by PHD2 mutants identified in germline DNA of patients with polycythemia","volume":"97","author":"Ladroue","year":"2012","journal-title":"Haematologica"},{"issue":"8","key":"10.1016\/j.heliyon.2024.e38020_bib39","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1002\/ajh.25150","article-title":"Genotype-phenotype correlation of hereditary erythrocytosis mutations, a single center experience","volume":"93","author":"Oliveira","year":"2018","journal-title":"Am. J. Hematol."},{"issue":"9","key":"10.1016\/j.heliyon.2024.e38020_bib40","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/ng.3067","article-title":"A genetic mechanism for Tibetan high-altitude adaptation","volume":"46","author":"Lorenzo","year":"2014","journal-title":"Nat. Genet."},{"issue":"8","key":"10.1016\/j.heliyon.2024.e38020_bib41","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/s41588-021-00904-0","article-title":"Activation of gamma-globin gene expression by GATA1 and NF-Y in hereditary persistence of fetal hemoglobin","volume":"53","author":"Doerfler","year":"2021","journal-title":"Nat. Genet."},{"issue":"3","key":"10.1016\/j.heliyon.2024.e38020_bib42","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1073\/pnas.0508423103","article-title":"A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis","volume":"103","author":"Percy","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.heliyon.2024.e38020_bib43","doi-asserted-by":"crossref","DOI":"10.1038\/srep18716","article-title":"Computational analysis of prolyl hydroxylase domain-containing protein 2 (PHD2) mutations promoting polycythemia insurgence in humans","volume":"6","author":"Minervini","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.heliyon.2024.e38020_bib44","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms12673","article-title":"Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases","volume":"7","author":"Chowdhury","year":"2016","journal-title":"Nat. Commun."}],"container-title":["Heliyon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405844024140510?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405844024140510?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:19:19Z","timestamp":1790713159000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2405844024140510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":44,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["S2405844024140510"],"URL":"https:\/\/doi.org\/10.1016\/j.heliyon.2024.e38020","relation":{},"ISSN":["2405-8440"],"issn-type":[{"value":"2405-8440","type":"print"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genetic modifications of EGLN1 reactivate HbF production in \u03b20-thalassemia\/HbE","name":"articletitle","label":"Article Title"},{"value":"Heliyon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.heliyon.2024.e38020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"e38020"}}