Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT30KEZZ)

• DOT Name: Zinc finger MYND domain-containing protein 10
• Synonyms: Protein BLu
• Gene Name: ZMYND10
• Related Disease:
  Primary ciliary dyskinesia 22
  Primary ciliary dyskinesia
• UniProt ID: ZMY10_HUMAN
• PDB ID: 2D8Q; 2DAN
• Pfam ID: PF01753
• Sequence:
  MGDLELLLPGEAEVLVRGLRSFPLREMGSEGWNQQHENLEKLNMQAILDATVSQGEPIQE
  LLVTHGKVPTLVEELIAVEMWKQKVFPVFCRVEDFKPQNTFPIYMVVHHEASIINLLETV
  FFHKEVCESAEDTVLDLVDYCHRKLTLLVAQSGCGGPPEGEGSQDSNPMQELQKQAELME
  FEIALKALSVLRYITDCVDSLSLSTLSRMLSTHNLPCLLVELLEHSPWSRREGGKLQQFE
  GSRWHTVAPSEQQKLSKLDGQVWIALYNLLLSPEAQARYCLTSFAKGRLLKLRAFLTDTL
  LDQLPNLAHLQSFLAHLTLTETQPPKKDLVLEQIPEIWERLERENRGKWQAIAKHQLQHV
  FSPSEQDLRLQARRWAETYRLDVLEAVAPERPRCAYCSAEASKRCSRCQNEWYCCRECQV
  KHWEKHGKTCVLAAQGDRAK
• Function: Plays a role in axonemal structure organization and motility. Involved in axonemal pre-assembly of inner and outer dynein arms (IDA and ODA, respectively) for proper axoneme building for cilia motility. May act by indirectly regulating transcription of dynein proteins.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 22	DISGBMVX	Definitive	Autosomal recessive	[1]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[2]

3 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 Zinc finger MYND domain-containing protein 10.	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc finger MYND domain-containing protein 10.	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Zinc finger MYND domain-containing protein 10.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Zinc finger MYND domain-containing protein 10.	[4]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Zinc finger MYND domain-containing protein 10.	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Zinc finger MYND domain-containing protein 10.	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Zinc finger MYND domain-containing protein 10.	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Zinc finger MYND domain-containing protein 10.	[9]

References

• [1] 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.
• [2] Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia. Am J Hum Genet. 2013 Aug 8;93(2):346-56. doi: 10.1016/j.ajhg.2013.07.009. Epub 2013 Jul 25.
• [3] 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.
• [4] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [5] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [6] 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.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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.
• [10] Global and region-specific post-transcriptional and post-translational modifications of bisphenol A in human prostate cancer cells. Environ Pollut. 2019 Dec;255(Pt 2):113318. doi: 10.1016/j.envpol.2019.113318. Epub 2019 Oct 2.