Details of Drug Off-Target (DOT)

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

• DOT Name: Germ cell-less protein-like 1 (GMCL1)
• Synonyms: Spermatogenesis-associated protein 29
• Gene Name: GMCL1
• Related Disease:
  Non-insulin dependent diabetes
  Atrial fibrillation
  B-cell lymphoma
  Coronary atherosclerosis
  Coronary heart disease
  Leber hereditary optic neuropathy
  Mental disorder
  Myopia
  Krabbe disease
  Neuroblastoma
• UniProt ID: GMCL1_HUMAN
• Pfam ID: PF07707 ; PF00651
• Sequence:
  MGSLSSRVLRQPRPALAQQAQGARAGGSARRPDTGDDAAGHGFCYCAGSHKRKRSSGSFC
  YCHPDSETDEDEEEGDEQQRLLNTPRRKKLKSTSKYIYQTLFLNGENSDIKICALGEEWS
  LHKIYLCQSGYFSSMFSGSWKESSMNIIELEIPDQNIDVEALQVAFGSLYRDDVLIKPSR
  VVAILAAACLLQLDGLIQQCGETMKETVNVKTVCGYYTSAGTYGLDSVKKKCLEWLLNNL
  MTHQNVELFKELSINVMKQLIGSSNLFVMQVEMDIYTALKKWMFLQLVPSWNGSLKQLLT
  ETDVWFSKQRKDFEGMAFLETEQGKPFVSVFRHLRLQYIISDLASARIIEQDAVVPSEWL
  SSVYKQQWFAMLRAEQDSEVGPQEINKEELEGNSMRCGRKLAKDGEYCWRWTGFNFGFDL
  LVTYTNRYIIFKRNTLNQPCSGSVSLQPRRSIAFRLRLASFDSSGKLICSRTTGYQILTL
  EKDQEQVVMNLDSRLLIFPLYICCNFLYISPEKKN
• Function: Possible function in spermatogenesis. Enhances the degradation of MDM2 and increases the amount of p53 probably by modulating the nucleocytoplasmic transport.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[2]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[4]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[4]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Biomarker	[5]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[6]
Myopia	DISK5S60	Strong	Genetic Variation	[7]
Krabbe disease	DIS6H1IB	moderate	Biomarker	[8]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[9]

5 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 Germ cell-less protein-like 1 (GMCL1).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Germ cell-less protein-like 1 (GMCL1).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Germ cell-less protein-like 1 (GMCL1).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Germ cell-less protein-like 1 (GMCL1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Germ cell-less protein-like 1 (GMCL1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Germ cell-less protein-like 1 (GMCL1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Germ cell-less protein-like 1 (GMCL1).	[16]

References

• [1] Structure-function relationship in early diabetic retinopathy: a spatial correlation analysis with OCT and microperimetry.Eye (Lond). 2017 Jun;31(6):931-939. doi: 10.1038/eye.2017.27. Epub 2017 Mar 3.
• [2] Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.
• [3] 1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma.EMBO Mol Med. 2010 May;2(5):159-71. doi: 10.1002/emmm.201000067.
• [4] Polymorphism in glutamate-cysteine ligase modifier subunit gene is associated with impairment of nitric oxide-mediated coronary vasomotor function. Circulation. 2003 Sep 23;108(12):1425-7. doi: 10.1161/01.CIR.0000091255.63645.98. Epub 2003 Sep 15.
• [5] Macular Retinal Sublayer Thicknesses in G11778A Leber Hereditary Optic Neuropathy.Ophthalmic Surg Lasers Imaging Retina. 2016 Sep 1;47(9):802-10. doi: 10.3928/23258160-20160901-02.
• [6] Glutamate cysteine ligase (GCL) and self reported depression: an association study from the HUNT.J Affect Disord. 2011 Jun;131(1-3):207-13. doi: 10.1016/j.jad.2010.12.019. Epub 2011 Jan 31.
• [7] Increased Vertical Asymmetry of Macular Retinal Layers in Myopic Chinese Children.Curr Eye Res. 2019 Feb;44(2):225-235. doi: 10.1080/02713683.2018.1530360. Epub 2018 Oct 26.
• [8] Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system.Toxicol Appl Pharmacol. 2017 Mar 1;318:69-78. doi: 10.1016/j.taap.2017.01.008. Epub 2017 Jan 20.
• [9] Human neuroblastoma cells with MYCN amplification are selectively resistant to oxidative stress by transcriptionally up-regulating glutamate cysteine ligase.J Neurochem. 2010 May;113(4):819-25. doi: 10.1111/j.1471-4159.2010.06648.x. Epub 2010 Feb 17.
• [10] 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.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [14] 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.
• [15] 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.
• [16] 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.