Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Studying ultra-rare variants in STX1A uncovers a novel neurodevelopmental disorder

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout


  1. Jahn R, Scheller RH. SNAREs — engines for membrane fusion. Nat Rev Mol Cell Biol. 2006;7:631–43.

    Article  CAS  PubMed  Google Scholar 

  2. Quick MW. The role of SNARE proteins in trafficking and function of neurotransmitter transporters. Handb Exp Pharmacol. 2006;175:181–96.

    Article  CAS  Google Scholar 

  3. Luppe J, Sticht H, Lecoquierre F, Goldenberg A, Gorman KM, Molloy B, et al. Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy. Eur J Hum Genet. 2022;31:345–52.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Reuter MS, Tawamie H, Buchert R, Gebril OH, Froukh T, Thiel C, et al. Diagnostic yield and novel candidate genes by exome sequencing in 152 consanguineous families with neurodevelopmental disorders. JAMA Psychiatry. 2017;74:293–9.

    Article  PubMed  Google Scholar 

  5. Verhage M, Sørensen JB. SNAREopathies: diversity in mechanisms and symptoms. Neuron. Cell Press. 2020;107:22–37.

    CAS  Google Scholar 

  6. Südhof TC, Rothman JE. Membrane Fusion: grappling with SNARE and SM proteins. Science. 2009;323:474.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bennett MK, Calakos N, Scheller RH. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science. 1992;257:255–9.

    Article  CAS  PubMed  Google Scholar 

  8. Wolking S, May P, Mei D, Møller RS, Balestrini S, Helbig KL, et al. Clinical spectrum of STX1B-related epileptic disorders. Neurology. 2019;92:e1238–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Schubert J, Siekierska A, Langlois M, May P, Huneau C, Becker F, et al. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes. Nat Genet. 2014;46:1327–32.

    Article  CAS  PubMed  Google Scholar 

  10. Vlaskamp DRM, Rump P, Callenbach PMC, Vos YJ, Sikkema-Raddatz B, Van Ravenswaaij-Arts CMA, et al. Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy. Eur J Paediatr Neurol. 2016;20:489–92.

    Article  PubMed  Google Scholar 

  11. Nakamura K, Anitha A, Yamada K, Tsujii M, Iwayama Y, Hattori E, et al. Genetic and expression analyses reveal elevated expression of syntaxin 1A (STX1A) in high functioning autism. Int J Neuropsychopharmacol. 2008;11:1073–84.

    Article  CAS  PubMed  Google Scholar 

  12. Nakamura K, Iwata Y, Anitha A, Miyachi T, Toyota T, Yamada S, et al. Replication study of Japanese cohorts supports the role of STX1A in autism susceptibility. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:454–8.

    Article  CAS  PubMed  Google Scholar 

  13. Baghel R, Grover S, Kaur H, Jajodia A, Parween S, Sinha J, et al. Synergistic association of STX1A and VAMP2 with cryptogenic epilepsy in North Indian population. Brain Behav. 2016;6:490.

    Article  Google Scholar 

  14. Zhou J, Zheng Y, Liang G, Xu X, Liu J, Chen S, et al. Atypical deletion of Williams–Beuren syndrome reveals the mechanism of neurodevelopmental disorders. BMC Med Genomics. 2022;15:79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature [Internet]. 2020;581:434–43.

    Article  CAS  PubMed  Google Scholar 

  16. Stamberger H, Nikanorova M, Willemsen MH, Accorsi P, Angriman M, Baier H, et al. STXBP1 encephalopathy: a neurodevelopmental disorder including epilepsy. Neurology [Internet]. 2016;86:954–62.

    Article  CAS  PubMed  Google Scholar 

  17. Rohena L, Neidich J, Truitt Cho M, Gonzalez KD, Tang S, Devinsky O, et al. Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability. Rare Dis [Internet]. 2013;1:e26314.

    Article  PubMed  Google Scholar 

  18. Dhindsa RS, Bradrick SS, Yao X, Heinzen EL, Petrovski S, Krueger BJ, et al. Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis. Neurol Genet. 2015;1:e4.

Download references


No financial assistance was used for this article.

Author information

Authors and Affiliations



The article was written and conceptualized by E.V.G. and R.S.D.

Corresponding authors

Correspondence to Esmeralda Villavicencio Gonzalez or Ryan S. Dhindsa.

Ethics declarations

Competing interests

E.V.G. has no outside disclosures. R.S.D. is a paid consultant for AstraZeneca.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Villavicencio Gonzalez, E., Dhindsa, R.S. Studying ultra-rare variants in STX1A uncovers a novel neurodevelopmental disorder. Eur J Hum Genet 31, 973–974 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links