Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT306E8G)

• DOT Name: Probable ribonuclease ZC3H12B
• Synonyms: EC 3.1.-.-; MCP-induced protein 2; Zinc finger CCCH domain-containing protein 12B
• Gene Name: ZC3H12B
• Related Disease: Autism spectrum disorder
• UniProt ID: ZC12B_HUMAN
• PDB ID: 6SJD
• EC Number: 3.1.-.-
• Pfam ID: PF18561 ; PF11977 ; PF18039
• Sequence:
  MTATAEVETPKMEKSASKEEKQQPKQDSTEQGNADSEEWMSSESDPEQISLKSSDNSKSC
  QPRDGQLKKKEMHSKPHRQLCRSPCLDRPSFSQSSILQDGKLDLEKEYQAKMEFALKLGY
  AEEQIQSVLNKLGPESLINDVLAELVRLGNKGDSEGQINLSLLVPRGPSSREIASPELSL
  EDEIDNSDNLRPVVIDGSNVAMSHGNKEEFSCRGIQLAVDWFLDKGHKDITVFVPAWRKE
  QSRPDAPITDQDILRKLEKEKILVFTPSRRVQGRRVVCYDDRFIVKLAFDSDGIIVSNDN
  YRDLQVEKPEWKKFIEERLLMYSFVNDKFMPPDDPLGRHGPSLENFLRKRPIVPEHKKQP
  CPYGKKCTYGHKCKYYHPERANQPQRSVADELRISAKLSTVKTMSEGTLAKCGTGMSSAK
  GEITSEVKRVAPKRQSDPSIRSVAMEPEEWLSIARKPEASSVPSLVTALSVPTIPPPKSH
  AVGALNTRSASSPVPGSSHFPHQKASLEHMASMQYPPILVTNSHGTPISYAEQYPKFESM
  GDHGYYSMLGDFSKLNINSMHNREYYMAEVDRGVYARNPNLCSDSRVSHTRNDNYSSYNN
  VYLAVADTHPEGNLKLHRSASQNRLQPFPHGYHEALTRVQSYGPEDSKQGPHKQSVPHLA
  LHAQHPSTGTRSSCPADYPMPPNIHPGATPQPGRALVMTRMDSISDSRLYESNPVRQRRP
  PLCREQHASWDPLPCTTDSYGYHSYPLSNSLMQPCYEPVMVRSVPEKMEQLWRNPWVGMC
  NDSREHMIPEHQYQTYKNLCNIFPSNIVLAVMEKNPHTADAQQLAALIVAKLRAAR
• Function: May function as RNase and regulate the levels of target RNA species.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[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 Probable ribonuclease ZC3H12B.	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Probable ribonuclease ZC3H12B.	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable ribonuclease ZC3H12B.	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Probable ribonuclease ZC3H12B.	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Probable ribonuclease ZC3H12B.	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Probable ribonuclease ZC3H12B.	[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 decreases the methylation of Probable ribonuclease ZC3H12B.	[7]

References

• [1] 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.
• [2] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] 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.