Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5WC0Q8)

DOT Name KN motif and ankyrin repeat domain-containing protein 4 (KANK4)
Synonyms Ankyrin repeat domain-containing protein 38
Gene Name KANK4
Related Disease
Bipolar disorder ( )
Bronchopulmonary dysplasia ( )
Fuchs' endothelial dystrophy ( )
Nephrotic syndrome ( )
Rheumatoid arthritis ( )
UniProt ID
KANK4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12796 ; PF12075
Sequence
MEKTDAKDQSSQGDEEKDPPKSHPYSVETPYGFHLDLDFLKYVDDIEKGNTIKRIPIHRR
AKQAKFSTLPRNFSLPDSGARPPAAPPLQNWSPVVPREASLGTQEQNQSPPLGNAPQAST
SRSEVSYHRKALLAEATRQLEAAEPEDAELTFGSGRPQLLRASSMPATLLHSRASEEPGL
SLGPPAPPALPPLQGEGSVCDGTFEPAEGLAGFHSSSPRASTRIPELVQEGAEPPEGVVK
VPNHLPLPGPPFSFQNVLVVLEDKEDEHNAREAEVLFTPGSPTPSPPPLPSPIPENELLL
EEIELNISEIPPPPPVEVDMRSIGIRVTEESLGLARVDPGSISSLKQQVSALEGELSGRT
EELAQVRTALQQQEEEIKAREQRIRELEFTVAQLEGQFHQENAKDTQGQTDVMVNTDPVH
GLLTRESCDKGIEVNLLGSMESESWGHRGEENGLLWGPDGHKQGNQSPAERVLLPQLSLP
QGPEQVLTSSVHSFLSTELRIEEAGTEQEGGPQGGTRGAGGFLWGSDRKTPPAGREETSS
NLPGKEHPGRPPSSPTDATIGQYVKKIQELLQEQWNCLEHGYPELASAIKQPASKLSSIQ
SQLLSSLNLLLSAYSAQAHPPKEPPASSSSPPVEISPSTSLKSIMKKKDYGFRAGGNGTK
KNLQFVGVNGGYETTSSEETSGEDSTPEDLSDSEAEKKCDGPDHKHVKDAHLTCEAGQGI
PEGTCHAAQESGPGEEVPHSKAERYKPSEEFLNACRALSQHLPETGTTTDQLLRQSLNTI
SQEWFRVSSRKSSSPAVVASYLHEVQPHSPHFLKLLVNLADHNGNTALHYSVSHSNFSIV
KLLLETGVCNVDHQNKAGYTAVMITPLASAETNEDMAVVWKLLREGNVNIQATQGGQTAL
MLGVSHDREDMVQALLSCQADVNLQDHDGSSALMVACHHGNVDLVRLLLAHPACDSSLTD
KAGRTALSIALKSPTHMEIAGLLRAHAEQGRSLGL
Function May be involved in the control of cytoskeleton formation by regulating actin polymerization.
Tissue Specificity Strongly expressed in colon, liver, lung, skeletal muscle and kidney.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bipolar disorder DISAM7J2 Strong Genetic Variation [1]
Bronchopulmonary dysplasia DISO0BY5 Strong Biomarker [1]
Fuchs' endothelial dystrophy DISL7TXC Strong Genetic Variation [2]
Nephrotic syndrome DISSPSC2 Strong Genetic Variation [3]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 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 KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [5]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [7]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [8]
Quercetin DM3NC4M Approved Quercetin decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [10]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [11]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [12]
Decitabine DMQL8XJ Approved Decitabine affects the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [8]
Marinol DM70IK5 Approved Marinol decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [13]
Panobinostat DM58WKG Approved Panobinostat increases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [11]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [14]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [15]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [16]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [18]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [21]
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⏷ Show the Full List of 17 Drug(s)
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 decreases the methylation of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of KN motif and ankyrin repeat domain-containing protein 4 (KANK4). [20]
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References

1 A linkage and exome study implicates rare variants of KANK4 and CAP2 in bipolar disorder in a multiplex family.Bipolar Disord. 2020 Feb;22(1):70-78. doi: 10.1111/bdi.12815. Epub 2019 Aug 21.
2 Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.Nat Commun. 2017 Mar 30;8:14898. doi: 10.1038/ncomms14898.
3 KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. J Clin Invest. 2015 Jun;125(6):2375-84. doi: 10.1172/JCI79504. Epub 2015 May 11.
4 CD38 and E2F transcription factor 2 have uniquely increased expression in rheumatoid arthritis synovial tissues.Clin Exp Immunol. 2014 May;176(2):222-31. doi: 10.1111/cei.12268.
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 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
9 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
10 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
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 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
13 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.
14 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
15 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.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
19 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
20 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.
21 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.