Details of Drug Off-Target (DOT)

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

• DOT Name: DnaJ homolog subfamily C member 17 (DNAJC17)
• Gene Name: DNAJC17
• Related Disease:
  Congenital hypothyroidism
  Hypothyroidism
  Retinitis pigmentosa
• UniProt ID: DJC17_HUMAN
• PDB ID: 2D9O
• Pfam ID: PF00226 ; PF00076
• Sequence:
  MAVTKELLQMDLYALLGIEEKAADKEVKKAYRQKALSCHPDKNPDNPRAAELFHQLSQAL
  EVLTDAAARAAYDKVRKAKKQAAERTQKLDEKRKKVKLDLEARERQAQAQESEEEEESRS
  TRTLEQEIERLREEGSRQLEEQQRLIREQIRQERDQRLRGKAENTEGQGTPKLKLKWKCK
  KEDESKGGYSKDVLLRLLQKYGEVLNLVLSSKKPGTAVVEFATVKAAELAVQNEVGLVDN
  PLKISWLEGQPQDAVGRSHSGLSKGSVLSERDYESLVMMRMRQAAERQQLIARMQQEDQE
  GPPT
• Function: May negatively affect PAX8-induced thyroglobulin/TG transcription.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[1]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[2]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DnaJ homolog subfamily C member 17 (DNAJC17).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of DnaJ homolog subfamily C member 17 (DNAJC17).	[9]

8 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 DnaJ homolog subfamily C member 17 (DNAJC17).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DnaJ homolog subfamily C member 17 (DNAJC17).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DnaJ homolog subfamily C member 17 (DNAJC17).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of DnaJ homolog subfamily C member 17 (DNAJC17).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DnaJ homolog subfamily C member 17 (DNAJC17).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DnaJ homolog subfamily C member 17 (DNAJC17).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DnaJ homolog subfamily C member 17 (DNAJC17).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of DnaJ homolog subfamily C member 17 (DNAJC17).	[13]

References

• [1] DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components.Sci Rep. 2018 May 17;8(1):7794. doi: 10.1038/s41598-018-26093-1.
• [2] High-resolution melting analysis (HRM) for mutational screening of Dnajc17 gene in patients affected by thyroid dysgenesis.J Endocrinol Invest. 2018 Jun;41(6):711-717. doi: 10.1007/s40618-017-0795-7. Epub 2017 Nov 20.
• [3] Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies.Genet Med. 2016 Jun;18(6):554-62. doi: 10.1038/gim.2015.127. Epub 2015 Sep 10.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [9] 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.
• [10] 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.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.