Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8HORRZ)

• DOT Name: Growth hormone-regulated TBC protein 1 (GRTP1)
• Synonyms: TBC1 domain family member 6
• Gene Name: GRTP1
• Related Disease:
  Bipolar disorder
  Major depressive disorder
  Schizophrenia
• UniProt ID: GRTP1_HUMAN
• Pfam ID: PF00566
• Sequence:
  MQPAERSRVPRIDPYGFERPEDFDDAAYEKFFSSYLVTLTRRAIKWSRLLQGGGVPRSRT
  VKRYVRKGVPLEHRARVWMVLSGAQAQMDQNPGYYHQLLQGERNPRLEDAIRTDLNRTFP
  DNVKFRKTTDPCLQRTLYNVLLAYGHHNQGVGYCQGMNFIAGYLILITNNEEESFWLLDA
  LVGRILPDYYSPAMLGLKTDQEVLGELVRAKLPAVGALMERLGVLWTLLVSRWFICLFVD
  ILPVETVLRIWDCLFNEGSKIIFRVALTLIKQHQELILEATSVPDICDKFKQITKGSFVM
  ECHTFMQKIFSEPGSLSMATVAKLRESCRARLLAQG
• Function: May act as a GTPase-activating protein for Rab family protein(s).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

9 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 Growth hormone-regulated TBC protein 1 (GRTP1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Growth hormone-regulated TBC protein 1 (GRTP1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Growth hormone-regulated TBC protein 1 (GRTP1).	[8]

References

• [1] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.