Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKEFAHV)

• DOT Name: Cationic amino acid transporter 3 (SLC7A3)
• Synonyms: CAT-3; CAT3; Cationic amino acid transporter y+; Solute carrier family 7 member 3
• Gene Name: SLC7A3
• Related Disease: Autism spectrum disorder
• UniProt ID: CTR3_HUMAN
• Pfam ID: PF13520 ; PF13906
• Sequence:
  MPWQAFRRFGQKLVRRRTLESGMAETRLARCLSTLDLVALGVGSTLGAGVYVLAGEVAKD
  KAGPSIVICFLVAALSSVLAGLCYAEFGARVPRSGSAYLYSYVTVGELWAFTTGWNLILS
  YVIGTASVARAWSSAFDNLIGNHISKTLQGSIALHVPHVLAEYPDFFALGLVLLLTGLLA
  LGASESALVTKVFTGVNLLVLGFVMISGFVKGDVHNWKLTEEDYELAMAELNDTYSLGPL
  GSGGFVPFGFEGILRGAATCFYAFVGFDCIATTGEEAQNPQRSIPMGIVISLSVCFLAYF
  AVSSALTLMMPYYQLQPESPLPEAFLYIGWAPARYVVAVGSLCALSTSLLGSMFPMPRVI
  YAMAEDGLLFRVLARIHTGTRTPIIATVVSGIIAAFMAFLFKLTDLVDLMSIGTLLAYSL
  VSICVLILRYQPDQETKTGEEVELQEEAITTESEKLTLWGLFFPLNSIPTPLSGQIVYVC
  SSLLAVLLTALCLVLAQWSVPLLSGDLLWTAVVVLLLLLIIGIIVVIWRQPQSSTPLHFK
  VPALPLLPLMSIFVNIYLMMQMTAGTWARFGVWMLIGFAIYFGYGIQHSLEEIKSNQPSR
  KSRAKTVDLDPGTLYVHSV
• Function: Uniporter that mediates the uptake of cationic L-amino acids such as L-arginine, L-lysine and L-ornithine. The transport is sodium ions- and pH-independent, moderately trans-stimulated and is mediated by passive diffusion.
• Tissue Specificity: Highly expressed in thymus, uterus and testis . Detected at lower levels in brain, mammary gland, prostate, salivary gland and fetal spleen . In brain, highest expression in thalamus, hippocampus and amygdala .
• Reactome Pathway: Amino acid transport across the plasma membrane (R-HSA-352230)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[1]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cationic amino acid transporter 3 (SLC7A3).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cationic amino acid transporter 3 (SLC7A3).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cationic amino acid transporter 3 (SLC7A3).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Cationic amino acid transporter 3 (SLC7A3).	[5]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Cationic amino acid transporter 3 (SLC7A3).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cationic amino acid transporter 3 (SLC7A3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cationic amino acid transporter 3 (SLC7A3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cationic amino acid transporter 3 (SLC7A3).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cationic amino acid transporter 3 (SLC7A3).	[11]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cationic amino acid transporter 3 (SLC7A3).	[8]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.