Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5CPAUT)

• DOT Name: Chorion-specific transcription factor GCMa (GCM1)
• Synonyms: hGCMa; GCM motif protein 1; Glial cells missing homolog 1
• Gene Name: GCM1
• Related Disease:
  Adenoma
  Neoplasm
  Pre-eclampsia
  Seminoma
  Choriocarcinoma
  Eclampsia
  Hypertension, pregnancy-induced
  Placenta disorder
• UniProt ID: GCM1_HUMAN
• Pfam ID: PF03615
• Sequence:
  MEPDDFDSEDKEILSWDINDVKLPQNVKKTDWFQEWPDSYAKHIYSSEDKNAQRHLSSWA
  MRNTNNHNSRILKKSCLGVVVCGRDCLAEEGRKIYLRPAICDKARQKQQRKRCPNCDGPL
  KLIPCRGHGGFPVTNFWRHDGRFIFFQSKGEHDHPKPETKLEAEARRAMKKVNTAPSSVS
  LSLKGSTETRSLPGETQSQGSLPLTWSFQEGVQLPGSYSGHLIANTPQQNSLNDCFSFSK
  SYGLGGITDLTDQTSTVDPMKLYEKRKLSSSRTYSSGDLLPPSASGVYSDHGDLQAWSKN
  AALGRNHLADNCYSNYPFPLTSWPCSFSPSQNSSEPFYQQLPLEPPAAKTGCPPLWPNPA
  GNLYEEKVHVDFNSYVQSPAYHSPQEDPFLFTYASHPHQQYSLPSKSSKWDFEEEMTYLG
  LDHCNNDMLLNLCPLR
• Function: Transcription factor involved in the control of expression of placental growth factor (PGF) and other placenta-specific genes. Binds to the trophoblast-specific element 2 (TSE2) of the aromatase gene enhancer. Binds to the SYDE1 promoter. Has a central role in mediating the differentiation of trophoblast cells along both the villous and extravillous pathways in placental development.
• Tissue Specificity: Highly expressed in the placenta . Expressed in trophoblast cells of the villi .
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Pre-eclampsia	DISY7Q29	Strong	Altered Expression	[2]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[3]
Choriocarcinoma	DISDBVNL	moderate	Biomarker	[4]
Eclampsia	DISWPO8U	moderate	Altered Expression	[5]
Hypertension, pregnancy-induced	DISHNU25	moderate	Biomarker	[6]
Placenta disorder	DISUW4CP	moderate	Altered Expression	[5]

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 Chorion-specific transcription factor GCMa (GCM1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Chorion-specific transcription factor GCMa (GCM1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Chorion-specific transcription factor GCMa (GCM1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol decreases the expression of Chorion-specific transcription factor GCMa (GCM1).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Chorion-specific transcription factor GCMa (GCM1).	[9]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Chorion-specific transcription factor GCMa (GCM1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Chorion-specific transcription factor GCMa (GCM1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Chorion-specific transcription factor GCMa (GCM1).	[13]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the expression of Chorion-specific transcription factor GCMa (GCM1).	[15]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Chorion-specific transcription factor GCMa (GCM1).	[16]
T0070907	DMTKSVO	Investigative	T0070907 decreases the expression of Chorion-specific transcription factor GCMa (GCM1).	[9]

References

• [1] Expression of GCMB by intrathymic parathyroid hormone-secreting adenomas indicates their parathyroid cell origin.J Clin Endocrinol Metab. 2004 Jan;89(1):8-12. doi: 10.1210/jc.2003-030733.
• [2] Increased plasma mRNAs of placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) in mothers with pre-eclampsia.Hiroshima J Med Sci. 2006 Mar;55(1):9-15.
• [3] DNA hypomethylation and aberrant expression of the human endogenous retrovirus ERVWE1/syncytin-1 in seminomas.Retrovirology. 2017 Mar 17;14(1):20. doi: 10.1186/s12977-017-0342-9.
• [4] STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas.PLoS One. 2008;3(12):e3905. doi: 10.1371/journal.pone.0003905. Epub 2008 Dec 11.
• [5] Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia.Placenta. 2004 May;25(5):413-21. doi: 10.1016/j.placenta.2003.10.014.
• [6] Effects of reduced Gcm1 expression on trophoblast morphology, fetoplacental vascularity, and pregnancy outcomes in mice.Hypertension. 2012 Mar;59(3):732-9. doi: 10.1161/HYPERTENSIONAHA.111.183939. Epub 2012 Jan 23.
• [7] 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.
• [8] The psychoactive compound of Cannabis sativa, (9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover. Toxicology. 2015 Aug 6;334:94-103. doi: 10.1016/j.tox.2015.06.005. Epub 2015 Jun 9.
• [9] Regulation of the placental BCRP transporter by PPAR gamma. J Biochem Mol Toxicol. 2017 May;31(5):10.1002/jbt.21880. doi: 10.1002/jbt.21880. Epub 2016 Nov 23.
• [10] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Effects of Bisphenol A on endogenous retroviral envelopes expression and trophoblast fusion in BeWo cells. Reprod Toxicol. 2019 Oct;89:35-44. doi: 10.1016/j.reprotox.2019.07.001. Epub 2019 Jul 3.
• [16] Chlorpyrifos modifies the expression of genes involved in human placental function. Reprod Toxicol. 2012 Jun;33(3):331-8. doi: 10.1016/j.reprotox.2012.01.003. Epub 2012 Jan 21.