Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXAG4PL)

• DOT Name: POC1 centriolar protein homolog A (POC1A)
• Synonyms: Pix2; Proteome of centriole protein 1A; WD repeat-containing protein 51A
• Gene Name: POC1A
• Related Disease:
  Fanconi anemia complementation group Q
  Acute myocardial infarction
  Chromosomal disorder
  Ciliopathy
  Coronary atherosclerosis
  Coronary heart disease
  Fatty liver disease
  Male infertility
  Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome
  Type-1/2 diabetes
  Myocardial ischemia
  Obesity
  Breast cancer
  Breast carcinoma
• UniProt ID: POC1A_HUMAN
• Pfam ID: PF00400
• Sequence:
  MAAPCAEDPSLERHFKGHRDAVTCVDFSINTKQLASGSMDSCLMVWHMKPQSRAYRFTGH
  KDAVTCVNFSPSGHLLASGSRDKTVRIWVPNVKGESTVFRAHTATVRSVHFCSDGQSFVT
  ASDDKTVKVWATHRQKFLFSLSQHINWVRCAKFSPDGRLIVSASDDKTVKLWDKSSRECV
  HSYCEHGGFVTYVDFHPSGTCIAAAGMDNTVKVWDVRTHRLLQHYQLHSAAVNGLSFHPS
  GNYLITASSDSTLKILDLMEGRLLYTLHGHQGPATTVAFSRTGEYFASGGSDEQVMVWKS
  NFDIVDHGEVTKVPRPPATLASSMGNLPEVDFPVPPGRGRSVESVQSQPQEPVSVPQTLT
  STLEHIVGQLDVLTQTVSILEQRLTLTEDKLKQCLENQQLIMQRATP
• Function: Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1B to ensure centriole integrity and proper mitotic spindle formation.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fanconi anemia complementation group Q	DISHYVNK	Definitive	Autosomal recessive	[1]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[2]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[3]
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[4]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[2]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[5]
Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome	DISN8GYD	Strong	Autosomal recessive	[4]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[6]
Myocardial ischemia	DISFTVXF	moderate	Genetic Variation	[7]
Obesity	DIS47Y1K	moderate	Biomarker	[8]
Breast cancer	DIS7DPX1	Limited	Biomarker	[9]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of POC1 centriolar protein homolog A (POC1A).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of POC1 centriolar protein homolog A (POC1A).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of POC1 centriolar protein homolog A (POC1A).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of POC1 centriolar protein homolog A (POC1A).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of POC1 centriolar protein homolog A (POC1A).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of POC1 centriolar protein homolog A (POC1A).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of POC1 centriolar protein homolog A (POC1A).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of POC1 centriolar protein homolog A (POC1A).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of POC1 centriolar protein homolog A (POC1A).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of POC1 centriolar protein homolog A (POC1A).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of POC1 centriolar protein homolog A (POC1A).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of POC1 centriolar protein homolog A (POC1A).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of POC1 centriolar protein homolog A (POC1A).	[21]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of POC1 centriolar protein homolog A (POC1A).	[22]

References

• [1] Truncation of POC1A associated with short stature and extreme insulin resistance. J Mol Endocrinol. 2015 Oct;55(2):147-58. doi: 10.1530/JME-15-0090.
• [2] Mechanisms of Myocardial Infarction inPatients With Nonobstructive Coronary Artery Disease: Results From the Optical Coherence Tomography Study.JACC Cardiovasc Imaging. 2019 Nov;12(11 Pt 1):2210-2221. doi: 10.1016/j.jcmg.2018.08.022. Epub 2018 Oct 17.
• [3] The effect of associated structural malformations in the prediction of chromosomal abnormality risk of fetuses with echogenic bowel.J Matern Fetal Neonatal Med. 2016;29(1):41-5. doi: 10.3109/14767058.2014.986091. Epub 2014 Dec 5.
• [4] POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism. Am J Hum Genet. 2012 Aug 10;91(2):330-6. doi: 10.1016/j.ajhg.2012.05.025. Epub 2012 Jul 26.
• [5] LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A) Causes Growth Insufficiency and Male Infertility in Mice.PLoS Genet. 2015 Oct 23;11(10):e1005569. doi: 10.1371/journal.pgen.1005569. eCollection 2015 Oct.
• [6] Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study.Am J Clin Nutr. 2019 Apr 1;109(4):1197-1206. doi: 10.1093/ajcn/nqy362.
• [7] Effects of copper and zinc on ischemic heart disease and myocardial infarction: a Mendelian randomization study.Am J Clin Nutr. 2018 Aug 1;108(2):237-242. doi: 10.1093/ajcn/nqy129.
• [8] Bifidobacteria and its rice fermented products on diet induced obese mice: analysis of physical status, serum profile and gene expressions.Benef Microbes. 2018 Apr 25;9(3):441-452. doi: 10.3920/BM2017.0056. Epub 2018 Feb 7.
• [9] An Italian Delphi study to evaluate consensus on adjuvant endocrine therapy in premenopausal patients with breast cancer: the ERA project.BMC Cancer. 2018 Sep 27;18(1):932. doi: 10.1186/s12885-018-4843-2.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] 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.
• [15] 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.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] 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.
• [20] 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.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.