Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD34H3B)

• DOT Name: Meiosis inhibitor protein 1 (MEI1)
• Synonyms: Meiosis defective protein 1
• Gene Name: MEI1
• Related Disease:
  Azoospermia
  Hydatidiform mole, recurrent, 3
  Complete hydatidiform mole
• UniProt ID: MEI1_HUMAN
• Sequence:
  MAVRQAATAGTPGPRREEEAALLFERAHYRHDPRWLLPVTPRLCLACALELLPDPGVSLV
  RKKHMLSCFQDALVRHTSLVTQLVSQDQRVCIHFISVLFGLLCSMEDGSVTDLCIEVLIQ
  ITTQLKLEQTIRCLLDECHKELCNMPSMRGSLATLTLLGKLVDAIPALADELVMEHGNLM
  EHLLRGLVYPSEGIQASVCYLYGKLYSSPVAAEMLSGHFREKLFPLFLSILDGAQTKELQ
  INCLGLLRQLLKYDLFVSMIMNQDGLGESAKNIEGSSGNTSLPLVLKKLLLSRDETLQVA
  SAHCITAVLVHSPAKHASAFIHADIPEFLFEHLSSSSEVLVWSSCNCLTLLVEEPLFFSK
  CHTVYGIEAVVRSLQGSLKMNNIELHKQGLLLFAEILTRQPEEIKLFTSSAMCRDAGRAL
  QEAVSSPVLEVAAEALKATSAFLRKDHQSTPPVQYGELQALLEAMLNRCAEFSQTLLSRR
  PLGHASSRDSEKAILQRGKFLLSTLEGFRSACRLAIEFQSEPSAQENPFTAPSAKKEDTL
  EAFSEFLLSACDSLCIPMVMRHLEQTTHPALMEVFLSILHNLFVIVPHMKEKFSKKLASS
  SFIRLTLELKARFCSGLSHSALNQVCSNFLYYMCLNLLSAPEKTGPPSKEELSAVSELLQ
  HGLPQISSRSPESLAFLSDRQYMEGAARQRQYCILLLFYLAYIHEDRFVSEAELFEAVQS
  FLLSLQDQGERPPLVVFKASIYLLAICQDKDNTLRETMVSAIRKFLEGIPDLQLVYTHHP
  LLLRFFLLYPELMSRYGHRVLELWFFWEESSYEELDDVTSAGQPALPASLVVLFQLLRSI
  PSILLILLDLIYSSPVDTAHKVLISLRTFLRRNEDIQVGGLIRGHFLLILQRLLVEHGAS
  PSGASGNLPLLLSLLSLMQLRNVSEQELDSVAMKLLHQVSKLCGKCSPTDVDILQPSFNF
  LYWSLHQTTPSSQKRAAAVLLSSTGLMELLEKMLALTLAKADSPRTALLCSAWLLTASFS
  AQQHKGSLQVHQTLSVEMDQVLKALSFPKKKAALLSAAILCFLRTALRQSFSSALVALVP
  SGAQPLPATKDTVLAPLRMSQVRSLVIGLQNLLVQKDPLLSQACVGCLEALLDYLDARSP
  DIALHVASQPWNRFLLFTLLDAGENSFLRPEILRLMTLFMRYRSSSVLSHEEVGDVLQGV
  ALADLSTLSNTTLQALHGFFQQLQSMGHLADHSMAQTLQASLEGLPPSTSSGQPPLQDML
  CLGGVAVSLSHIRN
• Function: Required for normal meiotic chromosome synapsis. May be involved in the formation of meiotic double-strand breaks (DSBs) in spermatocytes.
• Tissue Specificity: Expressed predominantly in testis. Weakly expressed in spleen and thymus. Expressed in the ovaries, Fallopian tubes and uterus .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Genetic Variation	[1]
Hydatidiform mole, recurrent, 3	DIS612M6	Strong	Autosomal recessive	[2]
Complete hydatidiform mole	DIS5QPI0	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Meiosis inhibitor protein 1 (MEI1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Meiosis inhibitor protein 1 (MEI1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Meiosis inhibitor protein 1 (MEI1).	[8]

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 Meiosis inhibitor protein 1 (MEI1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Meiosis inhibitor protein 1 (MEI1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Meiosis inhibitor protein 1 (MEI1).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Meiosis inhibitor protein 1 (MEI1).	[9]

References

• [1] Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest.J Hum Genet. 2006;51(6):533-540. doi: 10.1007/s10038-006-0394-5. Epub 2006 May 9.
• [2] Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles. Am J Hum Genet. 2018 Nov 1;103(5):740-751. doi: 10.1016/j.ajhg.2018.10.007.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.