Details of Drug Off-Target (DOT)

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

• DOT Name: Zinc finger SWIM domain-containing protein 7
• Synonyms: SWIM domain-containing and Srs2-interacting protein 1 homolog; SWIM-type zinc finger domain-containing protein 7
• Gene Name: ZSWIM7
• Related Disease:
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Ovarian dysgenesis 10
  Colorectal adenoma
• UniProt ID: ZSWM7_HUMAN
• Pfam ID: PF04434
• Sequence:
  MAVVLPAVVEELLSEMAAAVQESARIPDEYLLSLKFLFGSSATQALDLVDRQSITLISSP
  SGRRVYQVLGSSSKTYTCLASCHYCSCPAFAFSVLRKSDSILCKHLLAVYLSQVMRTCQQ
  LSVSDKQLTDILLMEKKQEA
• Function: Involved in early stages of the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Required for meiotic progression, hence for fertility.
• Tissue Specificity: Expressed in ovary and testis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Strong	Autosomal recessive	[1]
Ovarian dysgenesis 10	DIS1Z5X2	Strong	Autosomal recessive	[2]
Colorectal adenoma	DISTSVHM	Limited	Unknown	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Zinc finger SWIM domain-containing protein 7.	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc finger SWIM domain-containing protein 7.	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Zinc finger SWIM domain-containing protein 7.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc finger SWIM domain-containing protein 7.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Zinc finger SWIM domain-containing protein 7.	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Zinc finger SWIM domain-containing protein 7.	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Zinc finger SWIM domain-containing protein 7.	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Zinc finger SWIM domain-containing protein 7.	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Zinc finger SWIM domain-containing protein 7.	[8]

References

• [1] 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.
• [2] Shu complex SWS1-SWSAP1 promotes early steps in mouse meiotic recombination. Nat Commun. 2018 Oct 10;9(1):3961. doi: 10.1038/s41467-018-06384-x.
• [3] 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.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.