Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT9UI89)

• DOT Name: Transport and Golgi organization protein 2 homolog (TANGO2)
• Gene Name: TANGO2
• Related Disease:
  Arrhythmia
  Cardiovascular disease
  Hereditary myoglobinuria
  Hypothyroidism
  Lactic acidosis
  Microcephaly
  Prostate cancer
  Prostate carcinoma
  Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome
  Sensorineural hearing loss disorder
  Obsolete metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
  Alternating hemiplegia of childhood
  Hypoglycemia
• UniProt ID: TNG2_HUMAN
• Pfam ID: PF05742
• Sequence:
  MCIIFFKFDPRPVSKNAYRLILAANRDEFYSRPSKLADFWGNNNEILSGLDMEEGKEGGT
  WLGISTRGKLAALTNYLQPQLDWQARGRGELVTHFLTTDVDSLSYLKKVSMEGHLYNGFN
  LIAADLSTAKGDVICYYGNRGEPDPIVLTPGTYGLSNALLETPWRKLCFGKQLFLEAVER
  SQALPKDVLIASLLDVLNNEEAQLPDPAIEDQGGEYVQPMLSKYAAVCVRCPGYGTRTNT
  IILVDADGHVTFTERSMMDKDLSHWETRTYEFTLQS
• Function: May be involved in lipid homeostasis.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arrhythmia	DISFF2NI	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Hereditary myoglobinuria	DIS9GJQA	Strong	CausalMutation	[1]
Hypothyroidism	DISR0H6D	Strong	CausalMutation	[1]
Lactic acidosis	DISZI1ZK	Strong	CausalMutation	[1]
Microcephaly	DIS2GRD8	Strong	CausalMutation	[1]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[3]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[3]
Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome	DISJGTGG	Strong	Autosomal recessive	[1]
Sensorineural hearing loss disorder	DISJV45Z	Strong	CausalMutation	[1]
Obsolete metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration	DISH37CW	Moderate	Autosomal recessive	[4]
Alternating hemiplegia of childhood	DISB31JE	Limited	Genetic Variation	[5]
Hypoglycemia	DISRCKR7	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transport and Golgi organization protein 2 homolog (TANGO2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transport and Golgi organization protein 2 homolog (TANGO2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transport and Golgi organization protein 2 homolog (TANGO2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transport and Golgi organization protein 2 homolog (TANGO2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transport and Golgi organization protein 2 homolog (TANGO2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transport and Golgi organization protein 2 homolog (TANGO2).	[11]

References

• [1] Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations. Am J Hum Genet. 2016 Feb 4;98(2):347-57. doi: 10.1016/j.ajhg.2015.12.008. Epub 2016 Jan 21.
• [2] 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.
• [3] Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes.Oncotarget. 2017 Jan 3;8(1):1495-1507. doi: 10.18632/oncotarget.13646.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [5] Homozygous TANGO2 Single Nucleotide Variants Presenting with Additional Manifestations Resembling Alternating Hemiplegia of Childhood-Expanding the Phenotype of a Recently Reported Condition.Neuropediatrics. 2019 Apr;50(2):122-125. doi: 10.1055/s-0038-1677514. Epub 2019 Jan 16.
• [6] Clinical presentation and proteomic signature of patients with TANGO2 mutations.J Inherit Metab Dis. 2020 Mar;43(2):297-308. doi: 10.1002/jimd.12156. Epub 2019 Aug 13.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.