Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZTY5KQ)

DOT Name GREB1-like protein (GREB1L)
Synonyms Growth regulation by estrogen in breast cancer 1-like protein
Gene Name GREB1L
Related Disease
Congenital anomaly of kidney and urinary tract ( )
Renal hypodysplasia/aplasia 3 ( )
Ear malformation ( )
Renal agenesis ( )
Renal hypodysplasia/aplasia 1 ( )
Bilateral renal agenesis ( )
Renal agenesis, unilateral ( )
Hearing loss, autosomal dominant 80 ( )
UniProt ID
GRB1L_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF20692 ; PF20688 ; PF20267 ; PF15782 ; PF20691
Sequence
MGNSYAGQLKSARFEEALHNSIEASLRCSSVVPRPIFSQLYLDPDQHPFSSADVKPKVED
LDKDLVNRYTQNGSLDFSNNLTVNEMEDDEDDEEMSDSNSPPIPYSQKPAPEGSCTTDGF
CQAGKDLRLVSLCMEQIDIPAGFLLVGAKSPNLPEHILVCAVDKRFLPDDHGKNALLGFS
GNCIGCGERGFRYFTEFSNHINLKLTTQPKKQKHLKYYLVRSSQGVLSKGPLICWKECRS
RQSSASCHSIKPSSSVSSTVTPENGTTNGYKSGFTQTDAANGNSSHGGKGSASSSTPAHT
GNYSLSPRPSYASGDQATMFISGPPKKRHRGWYPGSPLPQPGLVVPVPTVRPLSRTEPLL
SAPVPQTPLTGILQPRPIPAGETVIVPENLLSNSGVRPVILIGYGTLPYFYGNVGDIVVS
PLLVNCYKIPQLENKDLEKLGLTGSQFLSVENMILLTIQYLVRLGPDQVPLREEFEQIML
KAMQEFTLRERALQIGAQCVPVSPGQLPWLARLIASVSQDLVHVVVTQNSLAEGISETLR
TLSEMRHYQRLPDYVVVICASKIRGNEFCVVVLGQHQSRALAESMLTTSEFLKEISYELI
TGKVSFLASHFKTTSLGDDLDKLLEKMQQRRGDSVVTPFDGDLNECVSPQEAAAMIPTQN
LDLDNETFHIYQPQLTVARKLLSQVCAIADSGSQSLDLGHFSKVDFIIIVPRSEVLVQQT
LQRIRQSGVLVDLGLEENGTAHQRAEKYVVRLDNEIQTKFEVFMRRVKQNPYTLFVLVHD
NSHVELTSVISGSLSHSEPSHGLADRVINCREVLEAFNLLVLQVSSFPYTLQTQQSRISS
SNEVHWIQLDTGEDVGCEEKLYFGLSEYSKSLQWGITSPLLRCDETFEKMVNTLLERYPR
LHSMVVRCYLLIQQYSEALMALTTMASLRDHSTPETLSIMDDLISSPGKNKSGRGHMLII
RVPSVQLAMLAKERLQEVRDKLGLQYRFEIILGNPATELSVATHFVARLKSWRGNEPEEW
IPRTYQDLDGLPCIVILTGKDPLGETFPRSLKYCDLRLIDSSYLTRTALEQEVGLACCYV
SKEVIRGPTVALDLSGKEQERAAVSENDSDELLIDLERPQSNSSAVTGTSGSIMENGVSS
SSTADKSQKQSLTPSFQSPATSLGLDEGVSASSAGAGAGETLKQECDSLGPQMASSTTSK
PSSSSSGPRTLPWPGQPIRGCRGPQAALPPVVILSKAAYSLLGSQKSGKLPSSSSLLPHA
DVAWVSSLRPLLNKDMSSEEQSLYYRQWTLARQHHADYSNQLDPASGTRNFHPRRLLLTG
PPQVGKTGSYLQFLRILFRMLIRLLEVDVYDEEEINTDHNESSEVSQSEGEPWPDIESFS
KMPFDVSVHDPKYSLMSLVYTEKLAGVKQEVIKESKVEEPRKRETVSIMLTKYAAYNTFH
HCEQCRQYMDFTSASQMSDSTLHAFTFSSSMLGEEVQLYFIIPKSKESHFVFSKQGKHLE
SMRLPLVSDKNLNAVKSPIFTPSSGRHEHGLLNLFHAMEGISHLHLLVVKEYEMPLYRKY
WPNHIMLVLPGMFNNAGVGAARFLIKELSYHNLELERNRLEELGIKRQCVWPFIVMMDDS
CVLWNIHSVQEPSSQPMEVGVSSKNVSLKTVLQHIEATPKIVHYAILGIQKWSSKLTSQS
LKAPFSRCHVHDFILLNTDLTQNVQYDFNRYFCEDADFNLRTNSSGLLICRFNNFSLMKK
HVQVGGQRDFIIKPKIMVSESLAPILPLQYICAPDSEHTLLAAPAQFLLEKFLQHASYKL
FPKAIHNFRSPVLAIDCYLNIGPEVAICYISSRPHSSNVNCEGVFFSGLLLYLCDSFVGA
DLKKFKFLKGATLCVICQDRSSLRQTIVRLELEDEWQFRLRDEFQTANSSDDKPLYFLTG
RHV
Function Plays a major role in early metanephros and genital development.
Tissue Specificity Widely expressed, with prominent expression in the cochlea . Expressed at high levels in fetal kidney . In adult tissues, highest levels in vagina, cervix and epididymis .

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Congenital anomaly of kidney and urinary tract DIS84IVH Definitive Genetic Variation [1]
Renal hypodysplasia/aplasia 3 DISZWIFS Definitive Autosomal dominant [2]
Ear malformation DISVJGPS Strong Genetic Variation [3]
Renal agenesis DIS0M9AF Strong Genetic Variation [4]
Renal hypodysplasia/aplasia 1 DISOH8XN Strong Genetic Variation [4]
Bilateral renal agenesis DISOR5IA Supportive Autosomal recessive [5]
Renal agenesis, unilateral DIS53ZJ8 Supportive Autosomal dominant [5]
Hearing loss, autosomal dominant 80 DISFGAU5 Limited Autosomal dominant [3]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of GREB1-like protein (GREB1L). [6]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of GREB1-like protein (GREB1L). [7]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of GREB1-like protein (GREB1L). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of GREB1-like protein (GREB1L). [9]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of GREB1-like protein (GREB1L). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of GREB1-like protein (GREB1L). [11]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of GREB1-like protein (GREB1L). [12]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of GREB1-like protein (GREB1L). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of GREB1-like protein (GREB1L). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of GREB1-like protein (GREB1L). [16]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 Drug(s)
1 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 decreases the methylation of GREB1-like protein (GREB1L). [14]
------------------------------------------------------------------------------------

References

1 Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice.Am J Hum Genet. 2017 Nov 2;101(5):803-814. doi: 10.1016/j.ajhg.2017.09.026.
2 A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans. Genetics. 2017 Sep;207(1):215-228. doi: 10.1534/genetics.117.1125. Epub 2017 Jul 24.
3 De novo variants in GREB1L are associated with non-syndromic inner ear malformations and deafness. Hum Genet. 2018 Jul;137(6-7):459-470. doi: 10.1007/s00439-018-1898-8. Epub 2018 Jun 28.
4 Whole-exome sequencing identifies a GREB1L variant in a three-generation family with Mllerian and renal agenesis: a novel candidate gene in Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome. A case report.Hum Reprod. 2019 Sep 29;34(9):1838-1846. doi: 10.1093/humrep/dez126.
5 Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations. Am J Hum Genet. 2017 Nov 2;101(5):789-802. doi: 10.1016/j.ajhg.2017.09.018.
6 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
7 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.
8 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.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
12 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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 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.
16 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.