{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSyntaxin‐1B, encoded by STX1B, is a central component of the presynaptic release machinery that mediates synaptic vesicle fusion and neurotransmitter exocytosis. Multiple studies have demonstrated that mutations in STX1B are strongly associated with febrile seizures and epilepsy. For example, whole‐exome sequencing and zebrafish knockdown experiments revealed that truncating or in‐frame insertion/deletion mutations in STX1B result in seizure‐like behavior and enhanced temperature sensitivity, thereby establishing a critical role of STX1B in maintaining normal neuronal excitability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Transcriptome analyses in degenerative motor neuron disease also show significant downregulation of STX1B in conjunction with other synaptic genes, supporting a link between impaired synaptic function and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Further, expanded case series underscore a broadened epileptic spectrum in patients harboring STX1B mutations, including well‐characterized epilepsy syndromes and even sleep‐related hypermotor epilepsy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical presynaptic role, alternative splicing of the STX1B gene produces a unique isoform, STX1B‐DeltaTMD, that lacks the typical transmembrane domain and is directed to the nucleus via a non‐classical nuclear localization signal. This nucleoplasmic form colocalizes with nuclear structural proteins and mitotic apparatus components, and its expression levels have prognostic implications in primary brain tumors, illustrating the functional versatility of STX1B in both synaptic transmission and nuclear processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic association studies have also scrutinized STX1B variants in broader contexts. Polymorphisms in STX1B have been investigated for potential contributions to Parkinson’s disease susceptibility"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and Kawasaki disease, where an intronic variant was linked with intravenous immunoglobulin responsiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, analysis of warfarin dose variability in different populations revealed that an STX1B SNP was initially associated with dose requirement; however, this effect was explained by linkage disequilibrium with VKORC1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, STX1B has shown promise as a sensitive and specific neuroendocrine marker in breast carcinomas, further supporting its diverse biological roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julian Schubert, Aleksandra Siekierska, Mélanie Langlois, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3130"}], "href": "https://doi.org/10.1038/ng.3130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25362483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25362483"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anna Maria D'Erchia, Angela Gallo, Caterina Manzari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Massive transcriptome sequencing of human spinal cord tissues provides new insights into motor neuron degeneration in ALS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-10488-7"}], "href": "https://doi.org/10.1038/s41598-017-10488-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28855684"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28855684"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Stefan Wolking, Patrick May, Davide Mei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical spectrum of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "STX1B"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "-related epileptic disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000007089"}], "href": "https://doi.org/10.1212/WNL.0000000000007089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30737342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30737342"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Joao Peres, Francisco Antunes, Bilal Zonjy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sleep-related hypermotor epilepsy and peri-ictal hypotension in a patient with syntaxin-1B mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epileptic Disord (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1684/epd.2018.0996"}], "href": "https://doi.org/10.1684/epd.2018.0996"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30378543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30378543"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maria-Ioanna Stefanou, Debora Desideri, Justus Marquetand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Motor cortex excitability in seizure-free STX1B mutation carriers with a history of epilepsy and febrile seizures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Neurophysiol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clinph.2017.10.008"}], "href": "https://doi.org/10.1016/j.clinph.2017.10.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29101845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29101845"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Martin Krenn, Monika Schloegl, Ekaterina Pataraia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delineation of epileptic and neurodevelopmental phenotypes associated with variants in STX1B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Seizure (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.seizure.2021.02.027"}], "href": "https://doi.org/10.1016/j.seizure.2021.02.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33677401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33677401"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sandrine Pereira, Annick Massacrier, Patrice Roll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear localization of a novel human syntaxin 1B isoform."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2008.07.010"}], "href": "https://doi.org/10.1016/j.gene.2008.07.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18691641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18691641"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jian-Yong Wang, Mei-Ying Gong, Yang-Lie Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RIT2 and STX1B polymorphisms are associated with Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parkinsonism Relat Disord (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.parkreldis.2014.12.006"}], "href": "https://doi.org/10.1016/j.parkreldis.2014.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25534083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25534083"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "A Shendre, H W Wiener, D Zhi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case-parent trio study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2014.47"}], "href": "https://doi.org/10.1038/gene.2014.47"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25101798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25101798"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Z Luo, X Li, M Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel variants associated with warfarin stable dosage by use of a two-stage extreme phenotype strategy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jth.13542"}], "href": "https://doi.org/10.1111/jth.13542"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27740732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27740732"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "I S Hamadeh, M H Shahin, S M Lima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of GGCX, STX1B and FPGS Polymorphisms on Warfarin Dose Requirements in European-Americans and Egyptians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Transl Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cts.12385"}], "href": "https://doi.org/10.1111/cts.12385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26751406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26751406"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sándor Turkevi-Nagy, Ágnes Báthori, János Böcz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/pore.2021.1610039"}], "href": "https://doi.org/10.3389/pore.2021.1610039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34764822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34764822"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "YongPing Chen, XiaoQin Yuan, Bei Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "No association of FAM47E rs6812193, SCARB2 rs6825004 and STX1B rs4889603 polymorphisms with Parkinson's disease in a Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neural Transm (Vienna) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00702-015-1430-4"}], "href": "https://doi.org/10.1007/s00702-015-1430-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26224037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26224037"}]}]}]}