Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN0JAYL)

• DOT Name: Serine/threonine-protein kinase Nek10 (NEK10)
• Synonyms: EC 2.7.11.1; Never in mitosis A-related kinase 10; NimA-related protein kinase 10
• Gene Name: NEK10
• Related Disease:
  Breast cancer
  Breast carcinoma
  Ciliary dyskinesia, primary, 44
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Lung adenocarcinoma
  Lung carcinoma
  Lung squamous cell carcinoma
  Neoplasm
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
  Prostate carcinoma
  Uterine fibroids
  Primary ciliary dyskinesia
• UniProt ID: NEK10_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MPDQDKKVKTTEKSTDKQQEITIRDYSDLKRLRCLLNVQSSKQQLPAINFDSAQNSMTKS
  EPAIRAGGHRARGQWHESTEAVELENFSINYKNERNFSKHPQRKLFQEIFTALVKNRLIS
  REWVNRAPSIHFLRVLICLRLLMRDPCYQEILHSLGGIENLAQYMEIVANEYLGYGEEQH
  TVDKLVNMTYIFQKLAAVKDQREWVTTSGAHKTLVNLLGARDTNVLLGSLLALASLAESQ
  ECREKISELNIVENLLMILHEYDLLSKRLTAELLRLLCAEPQVKEQVKLYEGIPVLLSLL
  HSDHLKLLWSIVWILVQVCEDPETSVEIRIWGGIKQLLHILQGDRNFVSDHSSIGSLSSA
  NAAGRIQQLHLSEDLSPREIQENTFSLQAACCAALTELVLNDTNAHQVVQENGVYTIAKL
  ILPNKQKNAAKSNLLQCYAFRALRFLFSMERNRPLFKRLFPTDLFEIFIDIGHYVRDISA
  YEELVSKLNLLVEDELKQIAENIESINQNKAPLKYIGNYAILDHLGSGAFGCVYKVRKHS
  GQNLLAMKEVNLHNPAFGKDKKDRDSSVRNIVSELTIIKEQLYHPNIVRYYKTFLENDRL
  YIVMELIEGAPLGEHFSSLKEKHHHFTEERLWKIFIQLCLALRYLHKEKRIVHRDLTPNN
  IMLGDKDKVTVTDFGLAKQKQENSKLTSVVGTILYSCPEVLKSEPYGEKADVWAVGCILY
  QMATLSPPFYSTNMLSLATKIVEAVYEPVPEGIYSEKVTDTISRCLTPDAEARPDIVEVS
  SMISDVMMKYLDNLSTSQLSLEKKLERERRRTQRYFMEANRNTVTCHHELAVLSHETFEK
  ASLSSSSSGAASLKSELSESADLPPEGFQASYGKDEDRACDEILSDDNFNLENAEKDTYS
  EVDDELDISDNSSSSSSSPLKESTFNILKRSFSASGGERQSQTRDFTGGTGSRPRPALLP
  LDLLLKVPPHMLRAHIKEIEAELVTGWQSHSLPAVILRNLKDHGPQMGTFLWQASAGIAV
  SQRKVRQISDPIQQILIQLHKIIYITQLPPALHHNLKRRVIERFKKSLFSQQSNPCNLKS
  EIKKLSQGSPEPIEPNFFTADYHLLHRSSGGNSLSPNDPTGLPTSIELEEGITYEQMQTV
  IEEVLEESGYYNFTSNRYHSYPWGTKNHPTKR
• Function: Plays a role in the cellular response to UV irradiation. Mediates G2/M cell cycle arrest, MEK autoactivation and ERK1/2-signaling pathway activation in response to UV irradiation. In ciliated cells of airways, it is involved in the regulation of mucociliary transport.
• Tissue Specificity: Expressed in the lung.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Ciliary dyskinesia, primary, 44	DISZFMTO	Strong	Autosomal recessive	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[4]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[4]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[4]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[4]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[4]
Lung squamous cell carcinoma	DISXPIBD	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[4]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Genetic Variation	[4]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[4]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[6]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[7]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Serine/threonine-protein kinase Nek10 (NEK10).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine/threonine-protein kinase Nek10 (NEK10).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine-protein kinase Nek10 (NEK10).	[9]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Serine/threonine-protein kinase Nek10 (NEK10).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase Nek10 (NEK10).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Serine/threonine-protein kinase Nek10 (NEK10).	[13]

References

• [1] Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2.Nat Genet. 2009 May;41(5):585-90. doi: 10.1038/ng.354. Epub 2009 Mar 29.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] 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.
• [4] Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.Cancer Res. 2016 Sep 1;76(17):5103-14. doi: 10.1158/0008-5472.CAN-15-2980. Epub 2016 Apr 20.
• [5] Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients.Genes Chromosomes Cancer. 2019 Mar;58(3):164-174. doi: 10.1002/gcc.22712. Epub 2019 Jan 7.
• [6] Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.Nat Commun. 2018 Sep 7;9(1):3636. doi: 10.1038/s41467-018-05428-6.
• [7] A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance. Nat Med. 2020 Feb;26(2):244-251. doi: 10.1038/s41591-019-0730-x. Epub 2020 Jan 20.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [12] 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.
• [13] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.