Details of Drug Off-Target (DOT)

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

DOT Name Zinc finger protein ZFPM2
Synonyms Friend of GATA protein 2; FOG-2; Friend of GATA 2; hFOG-2; Zinc finger protein 89B; Zinc finger protein multitype 2
Gene Name ZFPM2
Related Disease
46,XY sex reversal 9 ( )
Diaphragmatic hernia 3 ( )
Tetralogy of fallot ( )
46,XY partial gonadal dysgenesis ( )
UniProt ID
FOG2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF21182 ; PF12874
Sequence
MSRRKQSKPRQIKRPLEDAIEDEEEECPSEETDIISKGDFPLEESFSTEFGPENLSCEEV
EYFCNKGDDEGIQETAESDGDTQSEKPGQPGVETDDWDGPGELEVFQKDGERKIQSRQQL
PVGTTWGPFPGKMDLNNNSLKTKAQVPMVLTAGPKWLLDVTWQGVEDNKNNCIVYSKGGQ
LWCTTTKAISEGEELIAFVVDFDSRLQAASQMTLTEGMYPARLLDSIQLLPQQAAMASIL
PTAIVNKDIFPCKSCGIWYRSERNLQAHLMYYCSGRQREAAPVSEENEDSAHQISSLCPF
PQCTKSFSNARALEMHLNSHSGVKMEEFLPPGASLKCTVCSYTADSVINFHQHLFSHLTQ
AAFRCNHCHFGFQTQRELLQHQELHVPSGKLPRESDMEHSPSATEDSLQPATDLLTRSEL
PQSQKAMQTKDASSDTELDKCEKKTQLFLTNQRPEIQPTTNKQSFSYTKIKSEPSSPRLA
SSPVQPNIGPSFPVGPFLSQFSFPQDITMVPQASEILAKMSELVHRRLRHGSSSYPPVIY
SPLMPKGATCFECNITFNNLDNYLVHKKHYCSSRWQQMAKSPEFPSVSEKMPEALSPNTG
QTSINLLNPAAHSADPENPLLQTSCINSSTVLDLIGPNGKGHDKDFSTQTKKLSTSSNND
DKINGKPVDVKNPSVPLVDGESDPNKTTCEACNITFSRHETYMVHKQYYCATRHDPPLKR
SASNKVPAMQRTMRTRKRRKMYEMCLPEQEQRPPLVQQRFLDVANLNNPCTSTQEPTEGL
GECYHPRCDIFPGIVSKHLETSLTINKCVPVSKCDTTHSSVSCLEMDVPIDLSKKCLSQS
ERTTTSPKRLLDYHECTVCKISFNKVENYLAHKQNFCPVTAHQRNDLGQLDGKVFPNPES
ERNSPDVSYERSIIKCEKNGNLKQPSPNGNLFSSHLATLQGLKVFSEAAQLIATKEENRH
LFLPQCLYPGAIKKAKGADQLSPYYGIKPSDYISGSLVIHNTDIEQSRNAENESPKGQAS
SNGCAALKKDSLPLLPKNRGMVIVNGGLKQDERPAANPQQENISQNPQHEDDHKSPSWIS
ENPLAANENVSPGIPSAEEQLSSIAKGVNGSSQAPTSGKYCRLCDIQFNNLSNFITHKKF
YCSSHAAEHVK
Function
Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA4, GATA5 and GATA6. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. Also required in gonadal differentiation, possibly be regulating expression of SRY. Probably acts a corepressor of NR2F2.
Tissue Specificity Widely expressed at low level.
KEGG Pathway
MicroR.s in cancer (hsa05206 )
Reactome Pathway
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
Transcriptional regulation of testis differentiation (R-HSA-9690406 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
46,XY sex reversal 9 DIS19A07 Strong Autosomal dominant [1]
Diaphragmatic hernia 3 DISKZ3NX Strong Autosomal dominant [2]
Tetralogy of fallot DISMHFNW Strong Autosomal dominant [3]
46,XY partial gonadal dysgenesis DISMNH0C Supportive Autosomal dominant [4]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
15 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 Zinc finger protein ZFPM2. [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Zinc finger protein ZFPM2. [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Zinc finger protein ZFPM2. [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Zinc finger protein ZFPM2. [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Zinc finger protein ZFPM2. [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Zinc finger protein ZFPM2. [10]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Zinc finger protein ZFPM2. [11]
Marinol DM70IK5 Approved Marinol increases the expression of Zinc finger protein ZFPM2. [12]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Zinc finger protein ZFPM2. [14]
Malathion DMXZ84M Approved Malathion increases the expression of Zinc finger protein ZFPM2. [15]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Zinc finger protein ZFPM2. [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Zinc finger protein ZFPM2. [18]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Zinc finger protein ZFPM2. [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Zinc finger protein ZFPM2. [20]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Zinc finger protein ZFPM2. [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 15 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Zinc finger protein ZFPM2. [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Zinc finger protein ZFPM2. [17]
------------------------------------------------------------------------------------

References

1 Drinking water and the prevalence of colorectal adenomas: an epidemiologic study in Telemark, Norway. Eur J Cancer Prev. 1992 Oct;1(6):423-8. doi: 10.1097/00008469-199210000-00005.
2 Fog2 is required for normal diaphragm and lung development in mice and humans. PLoS Genet. 2005 Jul;1(1):58-65. doi: 10.1371/journal.pgen.0010010. Epub 2005 Jun 17.
3 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.
4 Mutations in the FOG2/ZFPM2 gene are associated with anomalies of human testis determination. Hum Mol Genet. 2014 Jul 15;23(14):3657-65. doi: 10.1093/hmg/ddu074. Epub 2014 Feb 18.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
7 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
8 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.
9 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
10 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
11 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
12 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
13 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.
14 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
15 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
16 Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia. 2004 Jul-Aug;6(4):354-63. doi: 10.1593/neo.03478.
17 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.
18 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
19 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.
20 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
21 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.