STXBP1 References : Key Publications

Basic Biology/Function of STXBP1
Dulubova I, Sugita S, Hill S, et al. A conformational switch in syntaxin during exocytosis: role of munc18. EMBO J. 1999;18(16):4372-4382.10449403
Verhage M, Maia AS, Plomp JJ, et al. Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion. Science. 2000;287(5454):864-869.10657302
Toonen RFG, Wierda K, Sons, MS, et al. Munc18-1 Expression Levels Control Synapse Recovery by Regulating Readily Releasable Pool Size. Proc Natl Acad Sci.006;103(48):18332-18337.17119441
Dulubova I, Khvotchev M, Liu S, Huryeva I, Südhof TC, Rizo J. Munc18-1 binds directly to the neuronal SNARE complex. Proc Natl Acad Sci. 2007;104(8):2697-2702.17301226
Shen J, Tareste DC, Paumet F, Rothman JE, Melia TJ. Selective Activation of Cognate SNAREpins by Sec1/Munc18 Proteins. Cell. 2007;128(1):183-195.17218264
Toonen RFG, Verhage M. Munc18-1 in Secretion: Lonely Munc Joins SNARE Team and Takes Control. Trends Neurosci. 2007;30(11):564-572.17956762
Rizo J, Rosenmund C. Synaptic vesicle fusion. Nat Struct Mol Biol. 2008;15(7):665-674.18618940
Deak F, Xu Y, Chang WP, et al. Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. J Cell Biol. 2009;184(5):751-764.19255244
Han GA, Malintan NT, Saw NMN, et al. Munc18-1 domain-1 controls vesicle docking and secretion by interacting with syntaxin-1 and chaperoning it to the plasma membrane. Mol Biol Cell. 2011;22(21):4134-4149.21900502
Sudhof TC, Rizo J. Synaptic Vesicle Exocytosis. Cold Spring Harb Perspect Biol. 2011;3(12):a005637.22026965
Parisotto D, Pfau M, Scheutzow A, et al. An extended helical conformation in domain 3a of Munc18-1 provides a template for SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex assembly. J Biol Chem. 2014;289(14):9639-9650.24532794
Meijer M, Cijsouw T, Toonen RF, Verhage M. Synaptic Effects of Munc18-1 Alternative Splicing in Excitatory Hippocampal Neurons. Cousin MA, ed. PLOS ONE. 2015;10(9):e0138950.26407320
Rizo J, Xu J. The Synaptic Vesicle Release Machinery. Annu Rev Biophys. 2015;44:339-367.26098518
Shen C, Rathore SS, Yu H, et al. The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis. Nat Commun. 2015;6:8852.26572858
Chai YJ, Sierecki E, Tomatis VM, et al. Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation. J Cell Biol. 2016;214(6):705-718.27597756
Hamada N, Iwamoto I, Tabata H, Nagat KI. MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through defective cortical architecture during brain development. Acta Neuropathol Commun. 2017;5(1):9229191246
He E, Wierda K, van Westen R, et al. Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles. Nat Commun. 2017;8:1591528635948
Kovacevic J, Maroteaux G, Schut D, et al. Protein Instability, Haploinsufficiency, and Cortical Hyper-excitability Underlie STXBP1 Encephalopathy. Brain.2018;141(5)1350-1374.29538625
Campbell JR, Martchenko A, Sweeney ME, et al. Essential Role of Syntaxin-Binding Protein-1 in the Regulation of Glucagon-Like Peptide-1 Secretion. Endocrinology. 2020;161(5):bqaa039.32141504
Berkel AA, Santos TC, Shaweis H, Weering JRT, Toonen RF, Verhage M. Loss of MUNC18‐1 leads to retrograde transport defects in neurons. J Neurochem. 2021;157(3):450-466.33259669
Puntman DC, Arora S, Farina M, Toonen RF, Verhage M. Munc18-1 Is Essential for Neuropeptide Secretion in Neurons. J Neurosci. 2021;41(28):5980-5993.34103363
Van Berkel AA, Koopmans F, Gonzalez-Lozano MA, et al. Dysregulation of Synaptic and Developmental Transcriptomic/Proteomic Profiles upon Depletion of MUNC18-1. eneuro. 2022;9(6):ENEURO.0186-22.2022.36257704
Lammertse HCA, Mora A, Saarloos I, Toonen RF, Verhage M. Reduced Dynamin-I Levels in Neurons lacking MUNC18-1. J Cell Sci. 2022;135(22):jcs260132.36245272
Feninga FM, van Berkel AA, Nair A, Verhage M. An atypical, staged cell death pathway induced by depletion of SNARE-proteins MUNC18-1 of Syntaxin-1. J Neurosci. 2023;43(3):347-358.36517239
Taura Y, Tozawa T, Fujimoto T, et al. Myosin Va, a novel partner of STXBP1, is required to transport syntaxin1A to the plasma membrane. Neurosci. 2023;524:256-268.37315734
Genetype, Phenotype, and Clinical Features of STXBP1-RD
Saitsu H, Kata M, Mizuguchi T, et al. De Novo Mutations in the Gene Encoding STXBP1 (MUNC18-1) Cause Early Infantile Epileptic Encephalopathy. Nat Genet. 2008;40(6):782-788.18469812
Deprez L, Weckhuysen S, Holmgren P, et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology. 2010;75(13):1159-1165.20876469
Otsuka M, Oguni H, Liang JS, et al. STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome—Result of Japanese cohort study. Epilepsia. 2010;51(12):2449-2452.21204804
Saitsu H, Kato M, Okada I, et al. STXBP1 Mutations in Early Infantile Epileptic Encephalopathy with Suppression-burst Pattern. Epilepsia. 2010;51(12)2397-2405.20887364
Hamdan FF, Gauthier J, Dobrzeniecka S, et al. Intellectual disability without epilepsy associated with STXBP1 disruption. Eur J Hum Genet EJHG. 2011;19(5):607-609.21364700
Mignot C, Moutard ML, Trouillard O, et al. STXBP1-related Encephalopathy Presenting as Infantile Spasms and generalized Tremor in Three Patients. Epilepsia. 2011; 52(10):1820-1827.21762454
Saitsu H, Hoshino H, Kato M, et al. Paternal mosaicism of an STXBP1 mutation in OS. Clin Genet. 2011;80(5):484-488.21062273
Carvill GL, Weckhuysen S, McMahon JM, et al. GABRA1 and STXBP1: Novel genetic causes of Dravet syndrome. Neurology. 2014;82(14):1245-1253.24623842
Ramos-Miguel A, Hercher C, Beasley CL, et al. Loss of Munc18-1 long splice variant in GABAergic terminals is associated with cognitive decline and increased risk of dementia in a community sample. Mol Neurodegener. 2015;10(1):65.26628003
Gburek-Augustat J, Beck-Woedl S, Tzschach A, et al. Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome. Eur J Paediatr Neurol. 2016;20(4):661-665.27184330
Helbig KL, Farwell Hagman KD, Shinde DN, et al. Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. Genet Med. 2016;18(9):898-905.26795593
Stamberger H, Nikanorova M, Willemsen MH, et al. STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology. 2016;86(10):954-962.26865513
Suri M, Evers JMG, Laskowski RA, et al. Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1Mol Genet Genomic Med. 2017;5(5):495-507.28944233
Uddin M, Woodbury-Smite M, Chan A, et al. Germline and somatic mutations in STXBP1 with diverse neurodevelopmental phenotypes. Neurol Genet. 2017;3(6):e199.29264391
Lindy AS, Stosser MB, Butler E, et al. Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders. Epilepsia. 2018;59(5):1062-1071.29655203
Lanoue V, Chai YJ, Brouillet JZ, et al. STXBP1 encephalopathy: Connecting neurodevelopmental disorders with α-synucleinopathies? Neurology. 2019;93(3):114-123.31221716
Mehdi KA, Fouad B, Zouhair E., et al. Molecular Modeling and Dynamics Study of nsSNP in STXBP1 Gene in Early Infantile Epileptic Encephalopathy Disease. Biomed Res Int. 2019;4872101.31976320
O’Brien S, Ng-Cordell E, Astle DE, Scerif G, Baker K. STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics. J Neurodev Disord. 2019;11(1):17.31387522
Rezazadeh A, Uddin M, Snead OC, et al. STXBP1 encephalopathy is associated with awake bruxism. Epilepsy Behav. 2019;92:121-124.30654231
Ganesan S, Galer PD, Helbig KL, et al. A longitudinal footprint of genetic epilepsies using automated electronic medical record interpretation. Genet Med. 2020;22(12):2060-2070.32773773
Johannesen KM, Nikanorova N, Marjanovic D, et al. Utility of genetic testing for therapeutic decision-making in adults with epilepsy. Epilepsia. 2020;61(6):1234-1239.32427350
Lammertse HC, van Berkel AA, Iacomino M, et al. Homozygous STXBP1 Variant Causes Encephalopathy and Gain-of-Function in Synaptic Transmission. Brain. 2020;143(2):441-451.31855252
Lopez-Rivera JA, Perez-Palma E, Symonds J, et al. A catalogue of new incidence estimates of mongenic neurodevelopmental disorders caused by de novo variants. Brain. 2020;143(4):1099-1105.32168371
Symonds JD, McTague A. Epilepsy and developmental disorders: Next generation sequencing in the clinic. Eur J Paediatr Neurol. 2020;24:15-23.31882278
Verhage M, Sorensen JB. SNAREopathies: Diversity in mechanisms and symptoms. Neuron. 2020; 107(1):22-37.32559416
Abramov D, Guiberson NGL, Burré J. STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies. J Neurochem. 2021;157(2):165-178.32643187
Houtman SJ, Lammertse HCA, van Berkel AA, et al. STXBP1 syndrome is characterized by inhibition-dominated dynamics of resting-state EEG. Front Physiol. 2021;12:775172.35002760
Yang P, Broadbent R, Prasad C, et al. De novo STXBP1 Mutations in Two Patients With Developmental Delay With or Without Epileptic Seizures. Front Neurol. 2021;12:804078.35002943
Balagura G, Xian J, Riva A, et al. Epilepsy Course and Developmental Trajectories in STXBP1 -DEE. Neurol Genet. 2022;8(3):e676.35655584
Cali E, Rocca C, Salpietro V, Houlden H. Epileptic Phenotypes Associated With SNAREs and Related Synaptic Vesicle Exocytosis Machinery. Front Neurol. 2022;12:806506.35095745
Gillentine MA, Wang T, Eichler EE. Estimating the prevalence of de novo mongenic neurodevelopmental disorders from large cohort studies. Biomedicines. 2022;10(11):2865.36359385
Kobayahi H, Matsushige T, Hoshide M, et al. Discordant phenotypes in monozygotic twins with STXBP1 mutation: A case report. Seizure. 2022;101:8-10.35841834
Naseer MI, Abdulkareem AA, Rasool M, et al. Clinical whole exome sequencing revealed de novo heterozygous stop-gain and missense variants in the STXBP1 gene associated with epilepsy in Saudi families. Saudi J Biol Sci. 2022;29(7):103309.35663845
Spoto G, Valentini G, Saia MC, et al. Synaptopathies in Developmental and Epileptic Encephalopathies: A Focus on Pre-synaptic Dysfunction. Front Neurol. 2022;13:826211.35350397
Stamberger H, Crosiers D, Balagura G, et al. Natural History Study of STXBP1-Developmental and Epileptic Encephalopathy Into Adulthood. Neurology. 2022;99(3):e221-e233.35851549
Xian J, Parthasarathy S, Ruggiero SM, et al. Assessing the landscape of STXBP1-related disorders in 534 individuals. Brain J Neurol. 2022;145(5):1668-1683.35190816
Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer I. Rates of status epilepticus and sudden unexplained death in epilepsy in people with genetic developmental and epileptic encephalopathies. Neurology. 2023;100(16)e1712-e1722.36750385
Kessi M, Chen B, Shan LD, et al. Genotype-phenotype correlations of STXBP1 pathogenic variants and the treatment choices for STXBP1-related disorders in China. BMC Med Genomics. 2023;16:46.36882827
Sullivan KR, Ruggiero SM, Xian J, et al. A disease concept model for STXBP1-related disorders. Epilepsia Open. 2023;8(2):320-333.36625631
Thalwitzer KM, Driedger J, Xian J, et al. Natural history and developmental trajectories of individuals with disease-causing variants in STXBP1. Neurology. 2023;10.1212/WNL.000000000020755037407264
Wang H, Chen X, Liu Z, et al. Case report: A novel STXBP1 splice variant and the landscape of spicing-involved STXBP1-related disorders. Front Neurol. 2023;14:1146875.37056358
Preclinical Models/Therapies and Therapy Development
Hussain S. Developing a PPI inhibitor-based therapy for STXBP1 haploinsufficiency-associated epileptic disorders. Front Mol Neurosci. 2014;7:6.24550774
Dilena R, Striano P, Traverso M, et al. Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation. Brain Dev. 2015;38(1):128-131.26212315
Patzke C, Han Y, Covy J, et al. Analysis of conditional heterozygous STXBP1 mutations in human neurons. J Clin Invest. 2015;125(9):3560-3571.26280581
Grone BP, Marchese M, Hamling KR, et al. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish. PLOS ONE. 2016;11(3):e0151148.26963117
Stamberger H, Weckhuysen S, De Jonghe P. STXBP1 as a therapeutic target for epileptic encephalopathy. Expert Opin Ther Targets. 2017;21(11):1027-1036.28971703
Orock A, Logan S, Deak F. Munc18-1 Haploinsufficiency Impairs Learning and Memory by Reduced Synaptic Vessicular Release in a Model of Ohtahara Syndrome. Mol Cell Neurosci. 2018;88:33-42.29217410
Chen W, Cai ZL, Chao ES, et al. Stxbp1/Munc18-1 haploinsufficiency impairs inhibition and mediates key neurological features of STXBP1 encephalopathy. eLife. 2020;9:e48705.32073399
Lu Z, He S, Jiang J, et al. Base-edited cynomolgus monkeys mimic core symptoms of STXBP1 encephalopathy. Mol Ther. 2022;30(6):2163-2175.35283272
Guiberson NGL, Pineda A, Abramov D, et al. Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones. Nat Commun. 2018;9(1):3986.30266908
Zhu B, Mak JCH, Morris A, el al. Functional analysis of epilepsy-associated variants in STXBP1/Munc18-1 using humanized Caenorhabditis elegans. Epilepsia. 2020;61(4):810-821.32112430
Ichise E, Chiyonobu T, Ishikawa M, et al. Impaired neuronal activity and differential gene expression in STXBP1 encephalopathy patient iPSC-derived GABAergic neurons. Hum Mol Genet. 2021;30(14):1337-1348.33961044
Liu J, Salvati KA, Baraban SC. In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish. iScience. 2021;24(6):102558.34142057
Suo G, Cao X, Zheng Y, et al. A de novo nonsense mutatino of STXBP1 causes early-onset epileptic enchephalopathy. Epilepsy Behav. 2021;123:108245.34390894
Moog M, Baraban SC. Clemizole and trazodone are effective antiseizure treatments in a zebrafish model of STXBP1 disorder. Epilepsia Open. 2022;7(3):504-511.35451230
Nam JY, Teng LY, Cho K, et al. Effects of the ketogenic diet therapy in patients with STXBP1-related encephalopathy. Epilepsy Res. 2022;186:106993.35998430
Hopkins CE, McCormick K, Brock T, et al. Clinical variants in Caenorhabditis elegans expressing humanb STXBP1 reveal a novel class of pathogenic variants and classify variants of uncertain significance. Genet in Med Open. 2023;1(1):10.1016/j.gimo.2023.100823Link
Kim JH, Chen W, Chao ES, Chen H, Xue M. Glutamatergic and GABAergic neurons mediate distinct neurodevelopmental phenotypes of STXBP1 encephalopathy. bioRxiv. 2023;10.1101/2021.07.13.452234v1Link
McLeod F, Dimtsi A, Marshall AC, et al. Altered synaptic connectivity in an in vitro human model of STXBP1 encephalopathy. Brain. 2023;146(3):850-857.36315647