Details of Drug Off-Target (DOT)

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

• DOT Name: Zinc finger MYND domain-containing protein 15
• Gene Name: ZMYND15
• Related Disease:
  Spermatogenic failure 14
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
• UniProt ID: ZMY15_HUMAN
• Pfam ID: PF20179 ; PF01753
• Sequence:
  MEFVSGYRDEFLDFTALLFGWFRKFVAERGAVGTSLEGRCRQLEAQIRRLPQDPALWVLH
  VLPNHSVGISLGQGAEPGPGPGLGTAWLLGDNPPLHLRDLSPYISFVSLEDGEEGEEEEE
  EDEEEEKREDGGAGSTEKVEPEEDRELAPTSRESPQETNPPGESEEAAREAGGGKDGCRE
  DRVENETRPQKRKGQRSEAAPLHVSCLLLVTDEHGTILGIDLLVDGAQGTASWGSGTKDL
  APWAYALLCHSMACPMGSGDPRKPRQLTVGDARLHRELESLVPRLGVKLAKTPMRTWGPR
  PGFTFASLRARTCHVCHRHSFEAKLTPCPQCSAVLYCGEACLRADWQRCPDDVSHRFWCP
  RLAAFMERAGELATLPFTYTAEVTSETFNKEAFLASRGLTRGYWTQLSMLIPGPGFSRHP
  RGNTPSLSLLRGGDPYQLLQGDGTALMPPVPPHPPRGVFGSWQDYYTWRGLSLDSPIAVL
  LTYPLTVYYVITHLVPQSFPELNIQNKQSLKIHVVEAGKEFDLVMVFWELLVLLPHVALE
  LQFVGDGLPPESDEQHFTLQRDSLEVSVRPGSGISARPSSGTKEKGGRRDLQIKVSARPY
  HLFQGPKPDLVIGFNSGFALKDTWLRSLPRLQSLRVPAFFTESSEYSCVMDGQTMAVATG
  GGTSPPQPNPFRSPFRLRAADNCMSWYCNAFIFHLVYKPAQGSGARPAPGPPPPSPTPSA
  PPAPTRRRRGEKKPGRGARRRK
• Function: Acts as a transcriptional repressor through interaction with histone deacetylases (HDACs). May be important for spermiogenesis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spermatogenic failure 14	DISXNTCR	Strong	Autosomal recessive	[1]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Zinc finger MYND domain-containing protein 15.	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Zinc finger MYND domain-containing protein 15.	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Zinc finger MYND domain-containing protein 15.	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Zinc finger MYND domain-containing protein 15.	[6]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Zinc finger MYND domain-containing protein 15.	[7]

References

• [1] Zmynd15 encodes a histone deacetylase-dependent transcriptional repressor essential for spermiogenesis and male fertility. J Biol Chem. 2010 Oct 8;285(41):31418-26. doi: 10.1074/jbc.M110.116418. Epub 2010 Jul 30.
• [2] Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia. J Med Genet. 2014 Apr;51(4):239-44. doi: 10.1136/jmedgenet-2013-102102. Epub 2014 Jan 15.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [7] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.