Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT67F3JQ)

• DOT Name: Meiosis-specific nuclear structural protein 1 (MNS1)
• Gene Name: MNS1
• Related Disease:
  Fibrosarcoma
  Heterotaxy, visceral, 9, autosomal, with male infertility
  Male infertility
  Primary ciliary dyskinesia
• UniProt ID: MNS1_HUMAN
• PDB ID: 7UNG; 8J07
• Pfam ID: PF13868
• Sequence:
  MGSKRRNLSCSERHQKLVDENYCKKLHVQALKNVNSQIRNQMVQNENDNRVQRKQFLRLL
  QNEQFELDMEEAIQKAEENKRLKELQLKQEEKLAMELAKLKHESLKDEKMRQQVRENSIE
  LRELEKKLKAAYMNKERAAQIAEKDAIKYEQMKRDAEIAKTMMEEHKRIIKEENAAEDKR
  NKAKAQYYLDLEKQLEEQEKKKQEAYEQLLKEKLMIDEIVRKIYEEDQLEKQQKLEKMNA
  MRRYIEEFQKEQALWRKKKREEMEEENRKIIEFANMQQQREEDRMAKVQENEEKRLQLQN
  ALTQKLEEMLRQREDLEQVRQELYQEEQAEIYKSKLKEEAEKKLRKQKEMKQDFEEQMAL
  KELVLQAAKEEEENFRKTMLAKFAEDDRIELMNAQKQRMKQLEHRRAVEKLIEERRQQFL
  ADKQRELEEWQLQQRRQGFINAIIEEERLKLLKEHATNLLGYLPKGVFKKEDDIDLLGEE
  FRKVYQQRSEICEEK
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. May play a role in the control of meiotic division and germ cell differentiation through regulation of pairing and recombination during meiosis. Required for sperm flagella assembly. May play a role in the assembly and function of the outer dynein arm-docking complex (ODA-DC). ODA-DC mediates outer dynein arms (ODA) binding onto the axonemal doublet microtubules.
• Tissue Specificity: Expressed in nasal respiratory epithelium and in the sperm.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[1]
Heterotaxy, visceral, 9, autosomal, with male infertility	DISYTX66	Strong	Autosomal recessive	[2]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Primary ciliary dyskinesia	DISOBC7V	Disputed	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[12]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[14]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Meiosis-specific nuclear structural protein 1 (MNS1).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Meiosis-specific nuclear structural protein 1 (MNS1).	[17]

References

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• [2] MNS1 variant associated with situs inversus and male infertility. Eur J Hum Genet. 2020 Jan;28(1):50-55. doi: 10.1038/s41431-019-0489-z. Epub 2019 Sep 18.
• [3] 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.
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• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] 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.
• [12] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] 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.
• [15] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] 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.
• [18] 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.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.