Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB1MTOI)

• DOT Name: Alpha/beta hydrolase domain-containing protein 17C (ABHD17C)
• Synonyms: Abhydrolase domain-containing protein 17C; EC 3.1.2.22
• Gene Name: ABHD17C
• Related Disease:
  Atrial fibrillation
  Cardiovascular disease
• UniProt ID: AB17C_HUMAN
• EC Number: 3.1.2.22
• Pfam ID: PF12146
• Sequence:
  MPEPGPRMNGFSLGELCWLFCCPPCPSRIAAKLAFLPPEPTYTVLAPEQRGAGASAPAPA
  QATAAAAAAQPAPQQPEEGAGAGPGACSLHLSERADWQYSQRELDAVEVFFSRTARDNRL
  GCMFVRCAPSSRYTLLFSHGNAVDLGQMCSFYIGLGSRINCNIFSYDYSGYGVSSGKPSE
  KNLYADIDAAWQALRTRYGVSPENIILYGQSIGTVPTVDLASRYECAAVILHSPLMSGLR
  VAFPDTRKTYCFDAFPSIDKISKVTSPVLVIHGTEDEVIDFSHGLAMYERCPRAVEPLWV
  EGAGHNDIELYAQYLERLKQFISHELPNS
• Function: Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards NRAS and DLG4/PSD95.
• Reactome Pathway: RAS processing (R-HSA-9648002)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]

8 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 Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[8]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Alpha/beta hydrolase domain-containing protein 17C (ABHD17C).	[10]

References

• [1] Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.
• [2] 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.
• [3] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.