Details of Drug Off-Target (DOT)

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

• DOT Name: Inositol hexakisphosphate kinase 3 (IP6K3)
• Synonyms: InsP6 kinase 3; EC 2.7.4.21; Inositol hexaphosphate kinase 3
• Gene Name: IP6K3
• Related Disease:
  Hypothyroidism
  Rheumatoid arthritis
  Schizophrenia
  Hashimoto thyroiditis
• UniProt ID: IP6K3_HUMAN
• EC Number: 2.7.4.21
• Pfam ID: PF03770
• Sequence:
  MVVQNSADAGDMRAGVQLEPFLHQVGGHMSVMKYDEHTVCKPLVSREQRFYESLPLAMKR
  FTPQYKGTVTVHLWKDSTGHLSLVANPVKESQEPFKVSTESAAVAIWQTLQQTTGSNGSD
  CTLAQWPHAQLARSPKESPAKALLRSEPHLNTPAFSLVEDTNGNQVERKSFNPWGLQCHQ
  AHLTRLCSEYPENKRHRFLLLENVVSQYTHPCVLDLKMGTRQHGDDASEEKKARHMRKCA
  QSTSACLGVRICGMQVYQTDKKYFLCKDKYYGRKLSVEGFRQALYQFLHNGSHLRRELLE
  PILHQLRALLSVIRSQSSYRFYSSSLLVIYDGQEPPERAPGSPHPHEAPQAAHGSSPGGL
  TKVDIRMIDFAHTTYKGYWNEHTTYDGPDPGYIFGLENLIRILQDIQEGE
• Function: Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
• Tissue Specificity: Detected in brain.
• KEGG Pathway: Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway: Synthesis of pyrophosphates in the cytosol (R-HSA-1855167)
• BioCyc Pathway: MetaCyc:HS08619-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Hashimoto thyroiditis	DIS77CDF	Limited	Genetic Variation	[4]

12 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 Inositol hexakisphosphate kinase 3 (IP6K3).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Inositol hexakisphosphate kinase 3 (IP6K3).	[15]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [3] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [4] Genome-wide association analysis suggests novel loci for Hashimoto's thyroiditis.J Endocrinol Invest. 2019 May;42(5):567-576. doi: 10.1007/s40618-018-0955-4. Epub 2018 Oct 3.
• [5] 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.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] 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.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] 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.
• [15] 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.