Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1FHMW4)

• DOT Name: Meiotic recombination protein DMC1/LIM15 homolog (DMC1)
• Gene Name: DMC1
• Related Disease:
  Gastric ulcer
  Neoplasm
  Bloom syndrome
  Female hypogonadism
  Spermatogenic failure
• UniProt ID: DMC1_HUMAN
• PDB ID: 1V5W; 2ZJB; 4HYY; 6R3P; 7C98; 7C99; 7C9C; 7CGY; 8R2G
• Pfam ID: PF14520 ; PF08423
• Sequence:
  MKEDQVVAEEPGFQDEEESLFQDIDLLQKHGINVADIKKLKSVGICTIKGIQMTTRRALC
  NVKGLSEAKVDKIKEAANKLIEPGFLTAFEYSEKRKMVFHITTGSQEFDKLLGGGIESMA
  ITEAFGEFRTGKTQLSHTLCVTAQLPGAGGYPGGKIIFIDTENTFRPDRLRDIADRFNVD
  HDAVLDNVLYARAYTSEHQMELLDYVAAKFHEEAGIFKLLIIDSIMALFRVDFSGRGELA
  ERQQKLAQMLSRLQKISEEYNVAVFVTNQMTADPGATMTFQADPKKPIGGHILAHASTTR
  ISLRKGRGELRIAKIYDSPEMPENEATFAITAGGIGDAKE
• Function: Participates in meiotic recombination, specifically in homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks.
• Reactome Pathway: Meiotic recombination (R-HSA-912446)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric ulcer	DISBBGVO	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Bloom syndrome	DISKXQ7J	moderate	Biomarker	[3]
Female hypogonadism	DISWASB4	moderate	Genetic Variation	[4]
Spermatogenic failure	DIS3D1AI	Limited	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Meiotic recombination protein DMC1/LIM15 homolog (DMC1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Meiotic recombination protein DMC1/LIM15 homolog (DMC1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Meiotic recombination protein DMC1/LIM15 homolog (DMC1).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Meiotic recombination protein DMC1/LIM15 homolog (DMC1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Meiotic recombination protein DMC1/LIM15 homolog (DMC1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Meiotic recombination protein DMC1/LIM15 homolog (DMC1).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Meiotic recombination protein DMC1/LIM15 homolog (DMC1).	[12]

References

• [1] Gastroprotective potential of methanolic extract and dimethyl cardamonin from Campomanesia reitziana fruits in mice.Naunyn Schmiedebergs Arch Pharmacol. 2017 Jun;390(6):661-666. doi: 10.1007/s00210-017-1369-0. Epub 2017 Apr 1.
• [2] Dissecting the Recombination Mediator Activity of BRCA2 Using Biochemical Methods.Methods Enzymol. 2018;600:479-511. doi: 10.1016/bs.mie.2017.11.018.
• [3] Expression and nuclear localization of BLM, a chromosome stability protein mutated in Bloom's syndrome, suggest a role in recombination during meiotic prophase.J Cell Sci. 2000 Feb;113 ( Pt 4):663-72. doi: 10.1242/jcs.113.4.663.
• [4] DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing.J Med Genet. 2018 Mar;55(3):198-204. doi: 10.1136/jmedgenet-2017-104992. Epub 2018 Jan 13.
• [5] 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.
• [6] 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.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] 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.
• [10] Chlorophyllin significantly reduces benzo[a]pyrene-DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells. Environ Mol Mutagen. 2009 Mar;50(2):134-44.
• [11] 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.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.