Details of Drug Off-Target (DOT)

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

DOT Name WD repeat-containing protein 72
Gene Name WDR72
Related Disease
Amelogenesis imperfecta ( )
Amelogenesis imperfecta hypomaturation type 2A3 ( )
Amelogenesis imperfecta type 2 ( )
Renal tubular acidosis ( )
UniProt ID
WDR72_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00400
Sequence
MRTSLQAVALWGQKAPPHSITAIMITDDQRTIVTGSQEGQLCLWNLSHELKISAKELLFG
HSASVTCLARARDFSKQPYIVSAAENGEMCVWNVTNGQCMEKATLPYRHTAICYYHCSFR
MTGEGWLLCCGEYQDVLIIDAKTLAVVHSFRSSQFPDWINCMCIVHSMRIQEDSLLVVSV
AGELKVWDLSSSINSIQEKQDVYEKESKFLESLNCQTIRFCTYTERLLLVVFSKCWKVYD
YCDFSLLLTEVSRNGQFFAGGEVIAAHRILIWTEDGHSYIYQLLNSGLSKSIYPADGRVL
KETIYPHLLCSTSVQENKEQSRPFVMGYMNERKEPFYKVLFSGEVSGRITLWHIPDVPVS
KFDGSPREIPVTATWTLQDNFDKHDTMSQSIIDYFSGLKDGAGTAVVTSSEYIPSLDKLI
CGCEDGTIIITQALNAAKARLLEGGSLVKDSPPHKVLKGHHQSVTSLLYPHGLSSKLDQS
WMLSGDLDSCVILWDIFTEEILHKFFLEAGPVTSLLMSPEKFKLRGEQIICCVCGDHSVA
LLHLEGKSCLLHARKHLFPVRMIKWHPVENFLIVGCADDSVYIWEIETGTLERHETGERA
RIILNCCDDSQLVKSVLPIASETLKHKSIEQRSSSPYQLGPLPCPGLQVESSCKVTDAKF
CPRPFNVLPVKTKWSNVGFHILLFDLENLVELLLPTPLSDVDSSSSFYGGEVLRRAKSTV
EKKTLTLRKSKTACGPLSAEALAKPITESLAQGDNTIKFSEENDGIKRQKKMKISKKMQP
KPSRKVDASLTIDTAKLFLSCLLPWGVDKDLDYLCIKHLNILKLQGPISLGISLNEDNFS
LMLPGWDLCNSGMIKDYSGVNLFSRKVLDLSDKYTATLPNQVGIPRGLENNCDSLRESDT
IVYLLSRLFLVNKLVNMPLELACRVGSSFRMESIHNKMRGAGNDILNMSSFYSCLRNGKN
ESHVPEADLSLLKLISCWRDQSVQVTEAIQAVLLAEVQQHMKSLGKIPVNSQPVSMAENG
NCEMKQMLPKLEWTEELELQCVRNTLPLQTPVSPVKHDSNSNSANFQDVEDMPDRCALEE
SESPGEPRHHSWIAKVCPCKVS
Function
Plays a major role in formation of tooth enamel. Specifically required during the maturation phase of amelogenesis for normal formation of the enamel matrix and clearance of enamel proteins. May be involved in localization of the calcium transporter SLC24A4 to the ameloblast cell membrane.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Amelogenesis imperfecta DISGYR9E Definitive Autosomal recessive [1]
Amelogenesis imperfecta hypomaturation type 2A3 DISCE7GG Strong Autosomal recessive [2]
Amelogenesis imperfecta type 2 DISX8NN4 Supportive Autosomal recessive [2]
Renal tubular acidosis DISE1NDR Limited Autosomal recessive [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 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 WD repeat-containing protein 72. [4]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of WD repeat-containing protein 72. [5]
Tretinoin DM49DUI Approved Tretinoin increases the expression of WD repeat-containing protein 72. [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of WD repeat-containing protein 72. [7]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of WD repeat-containing protein 72. [9]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of WD repeat-containing protein 72. [10]
Panobinostat DM58WKG Approved Panobinostat increases the expression of WD repeat-containing protein 72. [11]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of WD repeat-containing protein 72. [12]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of WD repeat-containing protein 72. [13]
Ethanol DMDRQZU Approved Ethanol decreases the expression of WD repeat-containing protein 72. [14]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of WD repeat-containing protein 72. [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of WD repeat-containing protein 72. [16]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of WD repeat-containing protein 72. [17]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of WD repeat-containing protein 72. [12]
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⏷ Show the Full List of 14 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of WD repeat-containing protein 72. [8]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta. Am J Hum Genet. 2009 Nov;85(5):699-705. doi: 10.1016/j.ajhg.2009.09.014. Epub 2009 Oct 22.
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 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.
5 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
6 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.
7 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
8 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.
9 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
10 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
11 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
12 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
13 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
14 Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
17 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.