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All KERs

Showing 2451 to 2475 of 3081 KERs

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs

3154	828: Inhibition, Phospholipase A	177: Increase, Mitochondrial dysfunction	Mar 13, 2024	Mar 13, 2024	1 AOP 130: Phospholipase A2 (LPLA2) inhibitors leading to hepatotoxicity
511	468: Inhibition, PPAR alpha	451: Inhibition, Mitochondrial fatty acid beta-oxidation	Nov 29, 2016	Dec 3, 2016	1 AOP 58: NR1I3 (CAR) suppression leading to hepatic steatosis
799	798: Inhibition, Prolyl hydroxylases	799: Increased, HIF-1 heterodimer	Nov 29, 2016	Dec 3, 2016	1 AOP 122: Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
3369	798: Inhibition, Prolyl hydroxylases	590: N/A, hypoxia	Oct 25, 2024	Oct 25, 2024	1 AOP 546: Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms
716	724: Inhibition, Pyruvate dehydrogenase kinase (PDK) enzyme	726: Increased, Induction of pyruvate dehydrogenase (PDH)	Nov 29, 2016	Dec 3, 2016	1 AOP 108: Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)
585	584: Inhibition, sodium channel	585: Decreased, Sodium conductance 1	Nov 29, 2016	Dec 3, 2016	3 AOPs 91: Sodium channel inhibition leading to reduced survival 93: sodium channel inhibition leading to increased predation 94: Sodium channel inhibition leading to congenital malformations
590	584: Inhibition, sodium channel	444: Increased, Atrioventricular block and bradycardia	Nov 29, 2016	Dec 3, 2016	None
1242	584: Inhibition, sodium channel	1176: Decreased, sodium conductance 2	Nov 29, 2016	Dec 3, 2016	1 AOP 197: Sodium channel (Nav1.1) inhibition leading to population decline
3414	584: Inhibition, sodium channel	698: Altered, Action Potential	Nov 21, 2024	Nov 21, 2024	1 AOP 553: Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure
867	845: Inhibition, UROD	844: Oxidation, Uroporphyrinogen	Nov 29, 2016	Nov 29, 2016	None
1070	845: Inhibition, UROD	846: Accumulation, Highly carboxylated porphyrins	Nov 29, 2016	May 30, 2018	1 AOP 131: Aryl hydrocarbon receptor activation leading to uroporphyria
335	305: Inhibition, VegfR2	28: Reduction, Angiogenesis	Nov 29, 2016	Jul 20, 2022	1 AOP 43: Disruption of VEGFR Signaling Leading to Developmental Defects
1382	1294: Inhibition, Wnt pathway	1295: Defect of Embryogenesis	Feb 15, 2017	Feb 15, 2017	1 AOP 210: Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building
3331	2255: Activation of the innate immune response	272: Activation/Proliferation, T-cells	Aug 13, 2024	Aug 13, 2024	None
3341	2255: Activation of the innate immune response	2260: Activation of gluten-reactive CD4+ T cells	Sep 13, 2024	Jun 17, 2025	1 AOP 524: Gluten-driven immune activation leading to celiac disease in genetically predisposed individuals
2702	2037: Activation, IP3R	389: Increased, Intracellular Calcium overload	Jul 25, 2022	Jul 25, 2022	1 AOP 464: Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits
3037	2037: Activation, IP3R	1350: Increased, glutamate	Sep 8, 2023	Sep 8, 2023	1 AOP 490: Co-activation of IP3R and RyR leads to reduced IQ and increased socio-economic burden through non-cholinergic mechanisms
329	298: Insufficiency, Vascular	183: Abnormal, Morphogenesis	Nov 29, 2016	Dec 3, 2016	None
1036	298: Insufficiency, Vascular	1001: Increased, Developmental Defects	Nov 29, 2016	Jan 18, 2022	1 AOP 43: Disruption of VEGFR Signaling Leading to Developmental Defects
1836	1584: Interaction of α-diketones with arginine residues	1585: Proteasomal dysfunction	Jan 30, 2019	Jan 30, 2019	1 AOP 280: α-diketone-induced bronchiolitis obliterans
1017	979: Interference, nuclear localization of NFAT	981: Reduction, NFAT/AP-1 complex formation	Nov 29, 2016	Jul 2, 2021	1 AOP 154: Inhibition of Calcineurin Activity Leading to Impaired T-Cell Dependent Antibody Response
2497	1901: IFN-I response, antagonized	1847: SARS-CoV-2 production	Oct 24, 2021	Dec 14, 2023	5 AOPs 430: Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation 422: Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption 320: Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality 379: Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation 468: Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)
1118	1074: interruption, Ovulation	1076: Increased, circulating estrogen levels	Nov 29, 2016	Dec 3, 2016	1 AOP 169: GnRH pulse disruption leading to pituitary adenomas and carcinomas in the SD rat.
2490	1931: Disruption of the intestinal barrier	1497: Recruitment of inflammatory cells	Oct 19, 2021	Oct 19, 2021	None
2494	1931: Disruption of the intestinal barrier	1932: GI disorders	Oct 19, 2021	Oct 19, 2021	None

Key Event Relationships (KERs)

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