Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA0Z9RZ)

• DOT Name: Coiled-coil domain-containing protein 174 (CCDC174)
• Gene Name: CCDC174
• Related Disease:
  Neuroblastoma
  Myopathy
  Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome
• UniProt ID: CC174_HUMAN
• Pfam ID: PF13300
• Sequence:
  MDRRKKPLDVTASSLVDLKAELFRKQEEFKQEKLLKDSGVFGKPKTTNKKPSIWSKQNVG
  VSNRAEKDAEQKIEEQKTLDKAREKLEEKAKLYEKMTKGDFIDEEVEDMYLVDFTQKIID
  KRKEMEASGAHRDSQKAGERDDDEENLPEGEIPPPQDPSEEWVDYVDSLGRSRRCMRKDL
  PDLLEMDKNLQGRLFISPANEKTLLSEDMRKELQRQQWEEEEREALKRPMGPVHYEDIRE
  NEARQLGVGYFAFARDKELRNKQMKTLEMLREQTTDQRTKRENIKEKRKAILEARLAKLR
  QKKMKKSKEGGTEEENRDGDVIGPLPPEPEAVPTPRPAAQSSKVEVIVQERKDTKPGVPH
  IREWDRGKEFSFGYWSKRQSDLRAERDPEFAPPSDYFVGQKRTGFSSSQAWSRPGPAQSD
  PGQCPDQSHGPSPEHTSPTPAPDNPPQAPTVTFKTLDDMISYYKQVT
• Function: Probably involved in neuronal development.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Strong	Biomarker	[1]
Myopathy	DISOWG27	moderate	Genetic Variation	[1]
Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome	DISPNZ8V	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Coiled-coil domain-containing protein 174 (CCDC174).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Coiled-coil domain-containing protein 174 (CCDC174).	[10]

References

• [1] CDC174, a novel component of the exon junction complex whose mutation underlies a syndrome of hypotonia and psychomotor developmental delay. Hum Mol Genet. 2015 Nov 15;24(22):6485-91. doi: 10.1093/hmg/ddv357. Epub 2015 Sep 10.
• [2] 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.
• [3] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.