Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNO5X2M)

• DOT Name: Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2)
• Gene Name: HDHD2
• Related Disease: High blood pressure
• UniProt ID: HDHD2_HUMAN
• PDB ID: 3HLT
• Pfam ID: PF13344 ; PF13242
• Sequence:
  MAACRALKAVLVDLSGTLHIEDAAVPGAQEALKRLRGASVIIRFVTNTTKESKQDLLERL
  RKLEFDISEDEIFTSLTAARSLLERKQVRPMLLVDDRALPDFKGIQTSDPNAVVMGLAPE
  HFHYQILNQAFRLLLDGAPLIAIHKARYYKRKDGLALGPGPFVTALEYATDTKATVVGKP
  EKTFFLEALRGTGCEPEEAVMIGDDCRDDVGGAQDVGMLGILVKTGKYRASDEEKINPPP
  YLTCESFPHAVDHILQHLL

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
High blood pressure	DISY2OHH	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2).	[8]

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 Haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2).	[7]

References

• [1] Two candidate genes for two quantitative trait loci epistatically attenuate hypertension in a novel pathway.J Hypertens. 2015 Sep;33(9):1791-801; discussion 1801. doi: 10.1097/HJH.0000000000000626.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.