Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZMTD4R)

• DOT Name: Deleted in azoospermia-like (DAZL)
• Synonyms: DAZ homolog; DAZ-like autosomal; Deleted in azoospermia-like 1; SPGY-like-autosomal
• Gene Name: DAZL
• Related Disease:
  Advanced cancer
  Teratoma
  Female hypogonadism
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Testicular germ cell tumor
• UniProt ID: DAZL_HUMAN
• Pfam ID: PF18872 ; PF00076
• Sequence:
  MSTANPETPNSTISREASTQSSSAATSQGYILPEGKIMPNTVFVGGIDVRMDETEIRSFF
  ARYGSVKEVKIITDRTGVSKGYGFVSFFNDVDVQKIVESQINFHGKKLKLGPAIRKQNLC
  AYHVQPRPLVFNHPPPPQFQNVWTNPNTETYMQPTTTMNPITQYVQAYPTYPNSPVQVIT
  GYQLPVYNYQMPPQWPVGEQRSYVVPPAYSAVNYHCNEVDPGAEVVPNECSVHEATPPSG
  NGPQKKSVDRSIQTVVSCLFNPENRLRNSVVTQDDYFKDKRVHHFRRSRAMLKSV
• Function: RNA-binding protein, which is essential for gametogenesis in both males and females. Plays a central role during spermatogenesis. Acts by binding to the 3'-UTR of mRNA, specifically recognizing GUU triplets, and thereby regulating the translation of key transcripts.
• Tissue Specificity: Testis specific.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Teratoma	DIS6ICY4	Strong	Altered Expression	[2]
Female hypogonadism	DISWASB4	moderate	Altered Expression	[3]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Moderate	Autosomal recessive	[4]
Testicular germ cell tumor	DIS5RN24	Limited	Biomarker	[5]

11 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 Deleted in azoospermia-like (DAZL).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Deleted in azoospermia-like (DAZL).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Deleted in azoospermia-like (DAZL).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Deleted in azoospermia-like (DAZL).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Deleted in azoospermia-like (DAZL).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Deleted in azoospermia-like (DAZL).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Deleted in azoospermia-like (DAZL).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Deleted in azoospermia-like (DAZL).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Deleted in azoospermia-like (DAZL).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Deleted in azoospermia-like (DAZL).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Deleted in azoospermia-like (DAZL).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Deleted in azoospermia-like (DAZL).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Deleted in azoospermia-like (DAZL).	[13]

References

• [1] Gamma-aminobutyric acid transaminase genetic polymorphism is a candidate locus for responsiveness to opioid analgesics in patients with cancer pain: An exploratory study.Neuropsychopharmacol Rep. 2018 Dec;38(4):175-181. doi: 10.1002/npr2.12030. Epub 2018 Sep 14.
• [2] Mammalian germ cells are determined after PGC colonization of the nascent gonad.Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25677-25687. doi: 10.1073/pnas.1910733116. Epub 2019 Nov 21.
• [3] Premature ovarian failure (POF) syndrome: towards the molecular clinical analysis of its genetic complexity.Curr Med Chem. 2006;13(12):1397-410. doi: 10.2174/092986706776872943.
• [4] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [5] Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.Nat Genet. 2013 Jun;45(6):686-9. doi: 10.1038/ng.2635. Epub 2013 May 12.
• [6] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [12] 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.
• [13] 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.
• [14] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.