Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX6U72I)

• DOT Name: Zinc finger CCCH domain-containing protein 14
• Synonyms: Mammalian suppressor of tau pathology-2; MSUT-2; Renal carcinoma antigen NY-REN-37
• Gene Name: ZC3H14
• Related Disease:
  Autosomal recessive non-syndromic intellectual disability
  Intellectual disability
  Intellectual disability, autosomal recessive 56
• UniProt ID: ZC3HE_HUMAN
• Pfam ID: PF14608
• Sequence:
  MEIGTEISRKIRSAIKGKLQELGAYVDEELPDYIMVMVANKKSQDQMTEDLSLFLGNNTI
  RFTVWLHGVLDKLRSVTTEPSSLKSSDTNIFDSNVPSNKSNFSRGDERRHEAAVPPLAIP
  SARPEKRDSRVSTSSQESKTTNVRQTYDDGAATRLMSTVKPLREPAPSEDVIDIKPEPDD
  LIDEDLNFVQENPLSQKKPTVTLTYGSSRPSIEIYRPPASRNADSGVHLNRLQFQQQQNS
  IHAAKQLDMQSSWVYETGRLCEPEVLNSLEETYSPFFRNNSEKMSMEDENFRKRKLPVVS
  SVVKVKKFNHDGEEEEEDDDYGSRTGSISSSVSVPAKPERRPSLPPSKQANKNLILKAIS
  EAQESVTKTTNYSTVPQKQTLPVAPRTRTSQEELLAEVVQGQSRTPRISPPIKEEETKGD
  SVEKNQGTQQRQLLSRLQIDPVMAETLQMSQDYYDMESMVHADTRSFILKKPKLSEEVVV
  APNQESGMKTADSLRVLSGHLMQTRDLVQPDKPASPKFIVTLDGVPSPPGYMSDQEEDMC
  FEGMKPVNQTAASNKGLRGLLHPQQLHLLSRQLEDPNGSFSNAEMSELSVAQKPEKLLER
  CKYWPACKNGDECAYHHPISPCKAFPNCKFAEKCLFVHPNCKYDAKCTKPDCPFTHVSRR
  IPVLSPKPAVAPPAPPSSSQLCRYFPACKKMECPFYHPKHCRFNTQCTRPDCTFYHPTIN
  VPPRHALKWIRPQTSE
• Function: Involved in poly(A) tail length control in neuronal cells. Binds the polyadenosine RNA oligonucleotides.
• Tissue Specificity: Isoform 1 and isoform 6 are expressed in fetal and adult brain. Isoform 1 and isoform 6 are expressed in fetal and adult temporal lobe.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[1]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[2]
Intellectual disability, autosomal recessive 56	DISLV8JT	Limited	Autosomal dominant	[3]

5 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 Zinc finger CCCH domain-containing protein 14.	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Zinc finger CCCH domain-containing protein 14.	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Zinc finger CCCH domain-containing protein 14.	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Zinc finger CCCH domain-containing protein 14.	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Zinc finger CCCH domain-containing protein 14.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Zinc finger CCCH domain-containing protein 14.	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc finger CCCH domain-containing protein 14.	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger CCCH domain-containing protein 14.	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Zinc finger CCCH domain-containing protein 14.	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Zinc finger CCCH domain-containing protein 14.	[12]

References

• [1] Mutation of the conserved polyadenosine RNA binding protein, ZC3H14/dNab2, impairs neural function in Drosophila and humans. Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12390-5. doi: 10.1073/pnas.1107103108. Epub 2011 Jul 6.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.