Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6Q5UDC)

• DOT Name: Zinc finger C4H2 domain-containing protein
• Synonyms: Hepatocellular carcinoma-associated antigen 127
• Gene Name: ZC4H2
• Related Disease:
  Wieacker-Wolff syndrome
  Wieacker-Wolff syndrome, female-restricted
  X-linked syndromic intellectual disability
• UniProt ID: ZC4H2_HUMAN
• Pfam ID: PF10146
• Sequence:
  MADEQEIMCKLESIKEIRNKTLQMEKIKARLKAEFEALESEERHLKEYKQEMDLLLQEKM
  AHVEELRLIHADINVMENTIKQSENDLNKLLESTRRLHDEYKPLKEHVDALRMTLGLQRL
  PDLCEEEEKLSLDYFEKQKAEWQTEPQEPPIPESLAAAAAAAQQLQVARKQDTRQTATFR
  QQPPPMKACLSCHQQIHRNAPICPLCKAKSRSRNPKKPKRKQDE
• Function: Plays a role in interneurons differentiation. Involved in neuronal development and in neuromuscular junction formation.
• Tissue Specificity: Expressed in fetal tissues, including in brain, intestine, lung, kidney and muscle . Isoform 1 is expressed in numerous fetal brain regions. Isoform 3 is highly expressed in numerous fetal brain regions and spinal cord .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Wieacker-Wolff syndrome	DISHE589	Definitive	X-linked	[1]
Wieacker-Wolff syndrome, female-restricted	DISHNDD3	Definitive	X-linked	[1]
X-linked syndromic intellectual disability	DISG1YOH	Definitive	X-linked	[2]

6 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 Zinc finger C4H2 domain-containing protein.	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger C4H2 domain-containing protein.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Zinc finger C4H2 domain-containing protein.	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Zinc finger C4H2 domain-containing protein.	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Zinc finger C4H2 domain-containing protein.	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Zinc finger C4H2 domain-containing protein.	[9]

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 Zinc finger C4H2 domain-containing protein.	[8]

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] 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] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.
• [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.