Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXG6MX5)

• DOT Name: BUD13 homolog (BUD13)
• Gene Name: BUD13
• Related Disease:
  Coronary heart disease
  Hyperlipidemia
  Hypochondroplasia
  Trichohepatoenteric syndrome
  Coronary atherosclerosis
  Prostate cancer
  Prostate carcinoma
• UniProt ID: BUD13_HUMAN
• PDB ID: 5Z56; 5Z57; 5Z58; 6FF4; 6FF7; 7ABI; 7DVQ; 7QTT; 8CH6
• Pfam ID: PF09736
• Sequence:
  MAAAPPLSKAEYLKRYLSGADAGVDRGSESGRKRRKKRPKPGGAGGKGMRIVDDDVSWTA
  ISTTKLEKEEEEDDGDLPVVAEFVDERPEEVKQMEAFRSSAKWKLLGGHNEDLPSNRHFR
  HDTPDSSPRRVRHGTPDPSPRKDRHDTPDPSPRRARHDTPDPSPLRGARHDSDTSPPRRI
  RHDSSDTSPPRRARHDSPDPSPPRRPQHNSSGASPRRVRHDSPDPSPPRRARHGSSDISS
  PRRVHNNSPDTSRRTLGSSDTQQLRRARHDSPDLAPNVTYSLPRTKSGKAPERASSKTSP
  HWKESGASHLSFPKNSKYEYDPDISPPRKKQAKSHFGDKKQLDSKGDCQKATDSDLSSPR
  HKQSPGHQDSDSDLSPPRNRPRHRSSDSDLSPPRRRQRTKSSDSDLSPPRRSQPPGKKAA
  HMYSGAKTGLVLTDIQREQQELKEQDQETMAFEAEFQYAETVFRDKSGRKRNLKLERLEQ
  RRKAEKDSERDELYAQWGKGLAQSRQQQQNVEDAMKEMQKPLARYIDDEDLDRMLREQER
  EGDPMANFIKKNKAKENKNKKVRPRYSGPAPPPNRFNIWPGYRWDGVDRSNGFEQKRFAR
  LASKKAVEELAYKWSVEDM
• Function: Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[1]
Hyperlipidemia	DIS61J3S	Strong	Genetic Variation	[2]
Hypochondroplasia	DISHNE51	Strong	Genetic Variation	[2]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[3]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[1]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[4]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[4]

10 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 BUD13 homolog (BUD13).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of BUD13 homolog (BUD13).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BUD13 homolog (BUD13).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of BUD13 homolog (BUD13).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of BUD13 homolog (BUD13).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of BUD13 homolog (BUD13).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of BUD13 homolog (BUD13).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of BUD13 homolog (BUD13).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of BUD13 homolog (BUD13).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of BUD13 homolog (BUD13).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of BUD13 homolog (BUD13).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of BUD13 homolog (BUD13).	[13]

References

• [1] Impact of gender and age on the association of the BUD13-ZNF259 rs964184 polymorphism with coronary heart disease.Anatol J Cardiol. 2018 Jan;19(1):42-49. doi: 10.14744/AnatolJCardiol.2017.8002.
• [2] Association of the variants in the BUD13-ZNF259 genes and the risk of hyperlipidaemia.J Cell Mol Med. 2014 Jul;18(7):1417-28. doi: 10.1111/jcmm.12291. Epub 2014 Apr 30.
• [3] Interactions of single nucleotide polymorphisms with dietary calcium intake on the risk of metabolic syndrome.Am J Clin Nutr. 2012 Jan;95(1):231-40. doi: 10.3945/ajcn.111.022749. Epub 2011 Dec 14.
• [4] Genetic variants reflecting higher vitamin e status in men are associated with reduced risk of prostate cancer.J Nutr. 2014 May;144(5):729-33. doi: 10.3945/jn.113.189928. Epub 2014 Mar 12.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] 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.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.