Stx1a can refer to two entities. One is the prototype of Shiga toxin 1 in Escherichia coli, a potent bacterial toxin. The Stxs consist of an A subunit that halts protein synthesis in target cells by injuring the eukaryotic ribosome, and a B pentamer that binds to the cellular receptor globotriaosylceramide on endothelial cells. Stx1a and Stx2a exhibit differences in cytotoxicity, receptor binding, and structural characteristics [3]. Epidemiological data suggest Stx2a is more often associated with the serious manifestation of hemolytic-uremic syndrome in humans, and Stx1a reduces the toxicity of Stx2a both in vivo and in vitro [5].

The other is syntaxin 1A, a core protein of the neuronal SNARE complex that drives synaptic vesicle exocytosis, suspected to play a role in neurodevelopmental disorders. Ultra-rare variants in STX1A can cause a spectrum of intellectual disability, autism, and epilepsy. Missense variants may lead to an STX1A-related developmental epileptic encephalopathy through a weakened inhibitory STX1A-STXBP1 interaction, while in-frame deletions may cause an STX1A-related intellectual disability and autism phenotype due to hampered SNARE complex formation [1]. In a Chinese Han population case-control study, STX1A genetic variants were found to contribute to the susceptibility of children with attention-deficit/hyperactivity disorder (ADHD) [2]. Also, STX1A has been associated with Asperger syndrome in a replication study [6]. In gastric cancer, STX1A overexpression is observed, and its knockdown inhibits cell proliferation and induces ferroptosis by impairing mitochondrial respiration, suggesting it may be a therapeutic target for overcoming chemoresistance [4].

In summary, Stx1a as a Shiga toxin plays a role in the pathogenesis of related diseases by its unique structure and function in disrupting host cell protein synthesis. As syntaxin 1A, it is crucial in neurodevelopmental processes and is associated with various neurodevelopmental disorders. Its role in gastric cancer through regulating ferroptosis also shows its significance in cancer research. Studies on Stx1a help in understanding disease mechanisms and may provide potential therapeutic targets.

References:

1. Luppe, Johannes, Sticht, Heinrich, Lecoquierre, François, Abou Jamra, Rami, Platzer, Konrad. 2022. Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy. In European journal of human genetics : EJHG, 31, 345-352. doi:10.1038/s41431-022-01269-6. https://pubmed.ncbi.nlm.nih.gov/36564538/

2. Wang, Min, Gu, Xue, Huang, Xin, Chen, Xinzhen, Wu, Jing. 2019. STX1A gene variations contribute to the susceptibility of children attention-deficit/hyperactivity disorder: a case-control association study. In European archives of psychiatry and clinical neuroscience, 269, 689-699. doi:10.1007/s00406-019-01010-3. https://pubmed.ncbi.nlm.nih.gov/30976917/

3. Melton-Celsa, Angela R. . Shiga Toxin (Stx) Classification, Structure, and Function. In Microbiology spectrum, 2, EHEC-0024-2013. doi:10.1128/microbiolspec.EHEC-0024-2013. https://pubmed.ncbi.nlm.nih.gov/25530917/

4. Niu, Yan, Liu, Chunyu, Jia, Lizhou, Gan, Yanzi, Wen, Yongjun. 2025. STX1A regulates ferroptosis and chemoresistance in gastric cancer through mitochondrial function modulation. In Human cell, 38, 66. doi:10.1007/s13577-025-01195-x. https://pubmed.ncbi.nlm.nih.gov/40056239/

5. Petro, Courtney D, Trojnar, Eszter, Sinclair, James, O'Brien, Alison D, Melton-Celsa, Angela. 2019. Shiga Toxin Type 1a (Stx1a) Reduces the Toxicity of the More Potent Stx2a In Vivo and In Vitro. In Infection and immunity, 87, . doi:10.1128/IAI.00787-18. https://pubmed.ncbi.nlm.nih.gov/30670557/

6. Durdiaková, Jaroslava, Warrier, Varun, Banerjee-Basu, Sharmila, Baron-Cohen, Simon, Chakrabarti, Bhismadev. 2014. STX1A and Asperger syndrome: a replication study. In Molecular autism, 5, 14. doi:10.1186/2040-2392-5-14. https://pubmed.ncbi.nlm.nih.gov/24548729/