{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:31:59Z","timestamp":1786991519808,"version":"build-2736575974"},"reference-count":47,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005685","name":"Department of Genetics, University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005685","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002382","name":"King Faisal Specialist Hospital and Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP 2020\/38"],"award-info":[{"award-number":["RSP 2020\/38"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["FCC\/1\/1976-25"],"award-info":[{"award-number":["FCC\/1\/1976-25"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["REI\/1\/4446-01"],"award-info":[{"award-number":["REI\/1\/4446-01"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019345","name":"King Salman Center for Disability Research","doi-asserted-by":"publisher","award":["RAC# 2180-004"],"award-info":[{"award-number":["RAC# 2180-004"]}],"id":[{"id":"10.13039\/501100019345","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2022,7]]},"DOI":"10.1016\/j.jbc.2022.102018","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T04:47:11Z","timestamp":1651812431000},"page":"102018","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical, genetic, and functional characterization of the glycine receptor \u03b2-subunit A455P variant in a family affected by hyperekplexia syndrome"],"prefix":"10.1016","volume":"298","author":[{"given":"Ghada I.","family":"Aboheimed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha M.","family":"AlRasheed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultan","family":"Almudimeegh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-994X","authenticated-orcid":false,"given":"Karla A.","family":"Pe\u00f1a-Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly J.","family":"Cardona-Londo\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa A.","family":"Salih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Z.","family":"Seidahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futwan","family":"Al-Mohanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"Colak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan T.","family":"Arold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-7507","authenticated-orcid":false,"given":"Namik","family":"Kaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud J.","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2022.102018_bib1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1756-6606-7-2","article-title":"The impact of human hyperekplexia mutations on glycine receptor structure and function","volume":"7","author":"Bode","year":"2014","journal-title":"Mol. Brain"},{"key":"10.1016\/j.jbc.2022.102018_bib2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.tig.2008.06.005","article-title":"The genetics of hyperekplexia: more than startle","volume":"24","author":"Harvey","year":"2008","journal-title":"Trends Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ana.410380115","article-title":"Mutational analysis of familial and sporadic hyperekplexia","volume":"38","author":"Shiang","year":"1995","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.jbc.2022.102018_bib4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/ng1293-351","article-title":"Mutations in the \u03b11-subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia","volume":"5","author":"Shiang","year":"1993","journal-title":"Nat. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib5","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/ng1814","article-title":"Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease","volume":"38","author":"Rees","year":"2006","journal-title":"Nat. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib6","doi-asserted-by":"crossref","first-page":"9612","DOI":"10.1523\/JNEUROSCI.1763-10.2010","article-title":"Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia","volume":"30","author":"Chung","year":"2010","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib7","doi-asserted-by":"crossref","first-page":"28975","DOI":"10.1074\/jbc.M112.372094","article-title":"Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease","volume":"287","author":"Carta","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.102018_bib8","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1046\/j.1460-9568.2002.02054.x","article-title":"Functional characterization of compound heterozygosity for GlyR \u03b11 mutations in the startle disease hyperekplexia","volume":"16","author":"Rea","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib9","doi-asserted-by":"crossref","first-page":"7394","DOI":"10.1073\/pnas.85.19.7394","article-title":"Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer","volume":"85","author":"Langosch","year":"1988","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2022.102018_bib10","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/0896-6273(93)90218-G","article-title":"Assembly of the inhibitory glycine receptor: identification of amino acid sequence motifs governing subunit stoichiometry","volume":"11","author":"Kuhse","year":"1993","journal-title":"Neuron"},{"key":"10.1016\/j.jbc.2022.102018_bib11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3389\/fnmol.2018.00317","article-title":"Structure-function relationships of glycine and GABAA receptors and their interplay with the scaffolding protein gephyrin","volume":"11","author":"Kasaragod","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib12","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/s41586-021-04022-z","article-title":"Architecture and assembly mechanism of native glycine receptors","volume":"599","author":"Zhu","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2022.102018_bib13","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1016\/j.neuron.2021.08.019","article-title":"Characterization of the subunit composition and structure of adult human glycine receptors","volume":"109","author":"Yu","year":"2021","journal-title":"Neuron"},{"key":"10.1016\/j.jbc.2022.102018_bib14","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1152\/physrev.00042.2003","article-title":"Molecular structure and function of the glycine receptor chloride channel","volume":"84","author":"Lynch","year":"2004","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.jbc.2022.102018_bib15","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1136\/jmg.33.5.435","article-title":"Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis","volume":"33","author":"Elmslie","year":"1996","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fnmol.2018.00167","article-title":"Functional consequences of the postnatal switch from neonatal to mutant adult glycine receptor \u03b11 subunits in the shaky mouse model of startle disease","volume":"11","author":"Schaefer","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib17","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1523\/JNEUROSCI.4346-11.2012","article-title":"The \u03b11K276E startle disease mutation reveals multiple intermediate states in the gating of glycine receptors","volume":"32","author":"Lape","year":"2012","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib18","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1113\/JP279803","article-title":"The startle disease mutation \u03b11S270T predicts shortening of glycinergic synaptic currents","volume":"598","author":"Wu","year":"2020","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.jbc.2022.102018_bib19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1469-7793.1998.025bu.x","article-title":"Properties of human glycine receptors containing the hyperekplexia mutation \u03b11(K276E), expressed in Xenopus oocytes","volume":"507","author":"Lewis","year":"1998","journal-title":"J.\u00a0Physiol."},{"key":"10.1016\/j.jbc.2022.102018_bib20","doi-asserted-by":"crossref","first-page":"33745","DOI":"10.1074\/jbc.M113.509240","article-title":"New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms","volume":"288","author":"Bode","year":"2013","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2022.102018_bib21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.parkreldis.2020.08.016","article-title":"A new family with GLRB-related hyperekplexia showing chorea in homo- and heterozygous variant carriers","volume":"79","author":"Estevez-Fraga","year":"2020","journal-title":"Parkinsonism Relat. Disord."},{"key":"10.1016\/j.jbc.2022.102018_bib22","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/hmg\/11.7.853","article-title":"Hyperekplexia associated with compound heterozygote mutations in the \u03b2-subunit of the human inhibitory glycine receptor (GLRB)","volume":"11","author":"Rees","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1399-0004.2011.01661.x","article-title":"Novel mutation in GLRB in a large family with hereditary hyperekplexia","volume":"81","author":"Al-Owain","year":"2012","journal-title":"Clin. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib24","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/hmg\/dds498","article-title":"GLRB is the third major gene of effect in hyperekplexia","volume":"22","author":"Chung","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1177\/0883073812441058","article-title":"Clinical features and genetic analysis of children with hyperekplexia in Korea","volume":"28","author":"Lee","year":"2013","journal-title":"J.\u00a0Child Neurol."},{"key":"10.1016\/j.jbc.2022.102018_bib26","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/85099","article-title":"Fast and reversible trapping of surface glycine receptors by gephyrin","volume":"4","author":"Meier","year":"2001","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib27","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.neuron.2005.01.028","article-title":"The \u03b2 subunit determines the ligand binding properties of synaptic glycine receptors","volume":"45","author":"Grudzinska","year":"2005","journal-title":"Neuron"},{"key":"10.1016\/j.jbc.2022.102018_bib28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.nbd.2012.12.001","article-title":"Novel missense mutations in the glycine receptor \u03b2 subunit gene (GLRB) in startle disease","volume":"52","author":"James","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.jbc.2022.102018_bib29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3389\/fnmol.2018.00291","article-title":"Impaired Glycine receptor trafficking in neurological diseases","volume":"11","author":"Schaefer","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib30","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s00439-013-1344-x","article-title":"The application of next-generation sequencing in the autozygosity mapping of human recessive diseases","volume":"132","author":"Alkuraya","year":"2013","journal-title":"Hum. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib31","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/cge.12131","article-title":"Impact of new genomic tools on the practice of clinical genetics in consanguineous populations: the Saudi experience","volume":"84","author":"Alkuraya","year":"2013","journal-title":"Clin. Genet."},{"key":"10.1016\/j.jbc.2022.102018_bib32","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1002\/j.1460-2075.1992.tb05529.x","article-title":"The atypical M2 segment of the \u03b2 subunit confers picrotoxinin resistance to inhibitory glycine receptor channels","volume":"11","author":"Pribilla","year":"1992","journal-title":"EMBO J."},{"key":"10.1016\/j.jbc.2022.102018_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0028105","article-title":"\u03b2 Subunit M2-M3 loop conformational changes are uncoupled from \u03b11\u03b2 glycine receptor channel gating: implications for human hereditary hyperekplexia","volume":"6","author":"Shan","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2022.102018_bib47","doi-asserted-by":"crossref","first-page":"745275","DOI":"10.3389\/fnmol.2021.745275","article-title":"Novel functional properties of missense mutations in the glycine receptor \u03b2 subunit in startle disease","volume":"14","author":"Piro","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.jbc.2022.102018_bib34","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/ene.14082","article-title":"Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination","volume":"27","author":"Chelban","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"10.1016\/j.jbc.2022.102018_bib35","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/brain\/awaa459","article-title":"Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking","volume":"144","author":"Sanderson","year":"2021","journal-title":"Brain"},{"key":"10.1016\/j.jbc.2022.102018_bib36","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/nprot.2013.075","article-title":"Sub-millisecond ligand probing of cell receptors with multiple solution exchange","volume":"8","author":"Sylantyev","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.jbc.2022.102018_bib37","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.jbc.2022.102018_bib38","doi-asserted-by":"crossref","first-page":"W430","DOI":"10.1093\/nar\/gkw306","article-title":"RaptorX-property: a web server for protein structure property prediction","volume":"44","author":"Wang","year":"2016","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.jbc.2022.102018_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1007112","article-title":"Pathogenicity and functional impact of non-frameshifting insertion\/deletion variation in the human genome","volume":"15","author":"Pagel","year":"2019","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.jbc.2022.102018_bib40","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A\u00a0method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jbc.2022.102018_bib41","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":"Nucl. Acids Res."},{"key":"10.1016\/j.jbc.2022.102018_bib42","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1093\/bioinformatics\/btw222","article-title":"PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation","volume":"32","author":"Tang","year":"2016","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jbc.2022.102018_bib43","doi-asserted-by":"crossref","first-page":"R232","DOI":"10.1186\/gb-2007-8-11-r232","article-title":"Determinants of protein function revealed by combinatorial entropy optimization","volume":"8","author":"Reva","year":"2007","journal-title":"Genome Biol."},{"key":"10.1016\/j.jbc.2022.102018_bib44","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucl. Acids Res."},{"key":"10.1016\/j.jbc.2022.102018_bib45","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nmeth0810-575","article-title":"MutationTaster evaluates disease-causing potential of sequence alterations","volume":"7","author":"Schwarz","year":"2010","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jbc.2022.102018_bib46","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat. Methods"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925822004586?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925822004586?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:32:38Z","timestamp":1762187558000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925822004586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":47,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["S0021925822004586"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2022.102018","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Clinical, genetic, and functional characterization of the glycine receptor \u03b2-subunit A455P variant in a family affected by hyperekplexia syndrome","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2022.102018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"102018"}}