Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLMQ1KS)

• DOT Name: TBC1 domain family member 19 (TBC1D19)
• Gene Name: TBC1D19
• Related Disease: Cardiovascular disease
• UniProt ID: TBC19_HUMAN
• Pfam ID: PF00566
• Sequence:
  MLQEESDLSLIIAQIVQKLKGSNLYSQLERQAWASLQRPEIKLESLKEDIKEFFKISGWE
  KKLQNAVYSELSVFPLPSHPAAPPEHLKEPLVYMRKAQGSWEKRILKSLNSMCTELSIPL
  ARKRPVGEQKELLNKWNEMGTDEPDLSLFRPVYAPKDFLEVLINLRNPNYENGDSLSFRT
  HLGLIQVPLKVKDIPELKECFVELGLNIGQLGIDDSTQVPPELFENEHVRIGQKVLAEQD
  SAAAQQYIRQGSPTALRAELWALILNISSQPEDVLYYEQLKTNVIQHDLLVDSLIYKDVK
  LTASNDDYYFVFEDYLYQVLLCFSRDTSVLSHFAFNSASPPKSYIRGKLGLEEYAVFYPP
  NGVIPFHGFSMYVAPLCFLYHEPSKLYQIFREMYVRFFFRLHSISSHPSGIVSLCLLFET
  LLQTYLPQLFYHLREIGAQPLRISFKWMVRAFSGYLATDQLLLLWDRILGYNSLEILAVL
  AAAVFAFRAVNLMEVTSLAAAEAVLADLSTLKVMPLLQIFLFATVT
• Function: May act as a GTPase-activating protein for Rab family protein(s).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of TBC1 domain family member 19 (TBC1D19).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TBC1 domain family member 19 (TBC1D19).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of TBC1 domain family member 19 (TBC1D19).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of TBC1 domain family member 19 (TBC1D19).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of TBC1 domain family member 19 (TBC1D19).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TBC1 domain family member 19 (TBC1D19).	[7]

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 increases the methylation of TBC1 domain family member 19 (TBC1D19).	[8]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.