Details of Drug Off-Target (DOT)

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

• DOT Name: Kinesin-like protein KIF3A (KIF3A)
• Synonyms: Microtubule plus end-directed kinesin motor 3A
• Gene Name: KIF3A
• Related Disease:
  Cowden disease
  Crohn disease
  Small intestine disorder
  Atopic dermatitis
  Bone development disease
  Clear cell renal carcinoma
  Cleft palate
  Cystic kidney disease
  Episodic kinesigenic dyskinesia 1
  Familial adenomatous polyposis
  Gastrointestinal stromal tumour
  Immune system disorder
  Isolated cleft palate
  Kidney failure
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Myocardial infarction
  Nasal polyp
  Neoplasm
  Nephronophthisis
  Non-small-cell lung cancer
  Polycystic kidney disease
  Polydactyly
  Psoriatic arthritis
  Adult glioblastoma
  Bladder cancer
  Glioblastoma multiforme
  Urinary bladder cancer
  Urinary bladder neoplasm
  Asthma
  Prostate cancer
  Prostate carcinoma
  Tuberculosis
• UniProt ID: KIF3A_HUMAN
• Pfam ID: PF00225
• Sequence:
  MPINKSEKPESCDNVKVVVRCRPLNEREKSMCYKQAVSVDEMRGTITVHKTDSSNEPPKT
  FTFDTVFGPESKQLDVYNLTARPIIDSVLEGYNGTIFAYGQTGTGKTFTMEGVRAIPELR
  GIIPNSFAHIFGHIAKAEGDTRFLVRVSYLEIYNEEVRDLLGKDQTQRLEVKERPDVGVY
  IKDLSAYVVNNADDMDRIMTLGHKNRSVGATNMNEHSSRSHAIFTITIECSEKGIDGNMH
  VRMGKLHLVDLAGSERQAKTGATGQRLKEATKINLSLSTLGNVISALVDGKSTHVPYRNS
  KLTRLLQDSLGGNSKTMMCANIGPADYNYDETISTLRYANRAKNIKNKARINEDPKDALL
  RQFQKEIEELKKKLEEGEEISGSDISGSEEDDDEEGEVGEDGEKRKKRRGKKKVSPDKMI
  EMQAKIDEERKALETKLDMEEEERNKARAELEKREKDLLKAQQEHQSLLEKLSALEKKVI
  VGGVDLLAKAEEQEKLLEESNMELEERRKRAEQLRRELEEKEQERLDIEEKYTSLQEEAQ
  GKTKKLKKVWTMLMAAKSEMADLQQEHQREIEGLLENIRQLSRELRLQMLIIDNFIPRDY
  QEMIENYVHWNEDIGEWQLKCVAYTGNNMRKQTPVPDKKEKDPFEVDLSHVYLAYTEESL
  RQSLMKLERPRTSKGKARPKTGRRKRSAKPETVIDSLLQ
• Function: Microtubule-based anterograde translocator for membranous organelles. Plus end-directed microtubule sliding activity in vitro. Plays a role in primary cilia formation. Plays a role in centriole cohesion and subdistal appendage organization and function. Regulates the formation of the subdistal appendage via recruitment of DCTN1 to the centriole. Also required for ciliary basal feet formation and microtubule anchoring to mother centriole.
• KEGG Pathway:
  Hedgehog sig.ling pathway (hsa04340)
  Motor proteins (hsa04814)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Hedgehog 'off' state (R-HSA-5610787)
  Intraflagellar transport (R-HSA-5620924)
  Activation of SMO (R-HSA-5635838)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Kinesins (R-HSA-983189)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cowden disease	DISMYKCE	Definitive	Biomarker	[1]
Crohn disease	DIS2C5Q8	Definitive	Biomarker	[1]
Small intestine disorder	DISF979Y	Definitive	Genetic Variation	[1]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[2]
Bone development disease	DISVKAZS	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Cleft palate	DIS6G5TF	Strong	Altered Expression	[5]
Cystic kidney disease	DISRT1LM	Strong	Altered Expression	[6]
Episodic kinesigenic dyskinesia 1	DISGVQMP	Strong	Altered Expression	[7]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[8]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[9]
Immune system disorder	DISAEGPH	Strong	Genetic Variation	[10]
Isolated cleft palate	DISV80CD	Strong	Altered Expression	[5]
Kidney failure	DISOVQ9P	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[11]
Lung carcinoma	DISTR26C	Strong	Biomarker	[11]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[12]
Myocardial infarction	DIS655KI	Strong	Biomarker	[13]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Nephronophthisis	DISXU4HY	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[15]
Polydactyly	DIS25BMZ	Strong	Biomarker	[3]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[16]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[17]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[18]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[17]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[18]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[18]
Asthma	DISW9QNS	Limited	Genetic Variation	[19]
Prostate cancer	DISF190Y	Limited	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[20]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[21]

14 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 Kinesin-like protein KIF3A (KIF3A).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Kinesin-like protein KIF3A (KIF3A).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Kinesin-like protein KIF3A (KIF3A).	[24]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Kinesin-like protein KIF3A (KIF3A).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kinesin-like protein KIF3A (KIF3A).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Kinesin-like protein KIF3A (KIF3A).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Kinesin-like protein KIF3A (KIF3A).	[28]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Kinesin-like protein KIF3A (KIF3A).	[29]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Kinesin-like protein KIF3A (KIF3A).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Kinesin-like protein KIF3A (KIF3A).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Kinesin-like protein KIF3A (KIF3A).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Kinesin-like protein KIF3A (KIF3A).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Kinesin-like protein KIF3A (KIF3A).	[22]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Kinesin-like protein KIF3A (KIF3A).	[36]

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 affects the methylation of Kinesin-like protein KIF3A (KIF3A).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Kinesin-like protein KIF3A (KIF3A).	[35]

References

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• [16] KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility.Oncotarget. 2017 Sep 8;8(56):95401-95411. doi: 10.18632/oncotarget.20727. eCollection 2017 Nov 10.
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• [21] Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis.Genes Immun. 2010 Jul;11(5):416-22. doi: 10.1038/gene.2010.26. Epub 2010 May 20.
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• [23] 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.
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• [25] 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.
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• [34] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [35] 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.
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