Details of Drug Off-Target (DOT)

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

• DOT Name: Trans-2,3-enoyl-CoA reductase-like (TECRL)
• Synonyms: EC 1.3.1.-; Steroid 5-alpha-reductase 2-like 2 protein
• Gene Name: TECRL
• Related Disease:
  Catecholaminergic polymorphic ventricular tachycardia
  Catecholaminergic polymorphic ventricular tachycardia 3
  Arrhythmia
  Catecholaminergic polymorphic ventricular tachycardia 1
• UniProt ID: TECRL_HUMAN
• EC Number: 1.3.1.-
• Pfam ID: PF02544 ; PF21696
• Sequence:
  MFKRHKSLASERKRALLSQRATRFILKDDMRNFHFLSKLVLSAGPLRPTPAVKHSKTTHF
  EIEIFDAQTRKQICILDKVTQSSTIHDVKQKFHKACPKWYPSRVGLQLECGGPFLKDYIT
  IQSIAASSIVTLYATDLGQQVSWTTVFLAEYTGPLLIYLLFYLRIPCIYDGKESARRLRH
  PVVHLACFCHCIHYIRYLLETLFVHKVSAGHTPLKNLIMSCAFYWGFTSWIAYYINHPLY
  TPPSFGNRQITVSAINFLICEAGNHFINVMLSHPNHTGNNACFPSPNYNPFTWMFFLVSC
  PNYTYEIGSWISFTVMTQTLPVGIFTLLMSIQMSLWAQKKHKIYLRKFNSYIHRKSAMIP
  FIL
• Tissue Specificity: Predominantly expressed in the heart and skeletal muscle.
• Reactome Pathway: Synthesis of very long-chain fatty acyl-CoAs (R-HSA-75876)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Catecholaminergic polymorphic ventricular tachycardia	DISSAS1A	Definitive	Autosomal recessive	[1]
Catecholaminergic polymorphic ventricular tachycardia 3	DISOPLNU	Definitive	Autosomal recessive	[2]
Arrhythmia	DISFF2NI	Strong	Genetic Variation	[3]
Catecholaminergic polymorphic ventricular tachycardia 1	DISKGB3F	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Trans-2,3-enoyl-CoA reductase-like (TECRL).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trans-2,3-enoyl-CoA reductase-like (TECRL).	[6]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Trans-2,3-enoyl-CoA reductase-like (TECRL).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Trans-2,3-enoyl-CoA reductase-like (TECRL).	[8]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Life-threatening arrhythmias with autosomal recessive TECRL variants. Europace. 2021 May 21;23(5):781-788. doi: 10.1093/europace/euaa376.
• [3] TECRL, a new life-threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT. EMBO Mol Med. 2016 Dec 1;8(12):1390-1408. doi: 10.15252/emmm.201505719. Print 2016 Dec.
• [4] A compound heterozygosity of Tecrl gene confirmed in a catecholaminergic polymorphic ventricular tachycardia family.Eur J Med Genet. 2019 Jul;62(7):103631. doi: 10.1016/j.ejmg.2019.01.018. Epub 2019 Feb 18.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [8] 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.