Details of Drug Off-Target (DOT)

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

• DOT Name: CWF19-like protein 1 (CWF19L1)
• Synonyms: C19L1
• Gene Name: CWF19L1
• Related Disease:
  Autosomal recessive spinocerebellar ataxia 17
  Cerebellar ataxia
  Fatty liver disease
  Intellectual disability
  Movement disorder
  Non-alcoholic fatty liver disease
• UniProt ID: C19L1_HUMAN
• Pfam ID: PF04677 ; PF04676
• Sequence:
  MAQKPLRLLACGDVEGKFDILFNRVQAIQKKSGNFDLLLCVGNFFGSTQDAEWEEYKTGI
  KKAPIQTYVLGANNQETVKYFQDADGCELAENITYLGRKGIFTGSSGLQIVYLSGTESLN
  EPVPGYSFSPKDVSSLRMMLCTTSQFKGVDILLTSPWPKCVGNFGNSSGEVDTKKCGSAL
  VSSLATGLKPRYHFAALEKTYYERLPYRNHIILQENAQHATRFIALANVGNPEKKKYLYA
  FSIVPMKLMDAAELVKQPPDVTENPYRKSGQEASIGKQILAPVEESACQFFFDLNEKQGR
  KRSSTGRDSKSSPHPKQPRKPPQPPGPCWFCLASPEVEKHLVVNIGTHCYLALAKGGLSD
  DHVLILPIGHYQSVVELSAEVVEEVEKYKATLRRFFKSRGKWCVVFERNYKSHHLQLQVI
  PVPISCSTTDDIKDAFITQAQEQQIELLEIPEHSDIKQIAQPGAAYFYVELDTGEKLFHR
  IKKNFPLQFGREVLASEAILNVPDKSDWRQCQISKEDEETLARRFRKDFEPYDFTLDD
• Tissue Specificity: Expressed in many brain regions, including cerebellum, thalamus and occipital, parietal and temporal lobes (at protein level). Also expressed in the spinal cord (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive spinocerebellar ataxia 17	DISW4IHJ	Strong	Autosomal recessive	[1]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[2]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[3]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[2]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[2]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CWF19-like protein 1 (CWF19L1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CWF19-like protein 1 (CWF19L1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CWF19-like protein 1 (CWF19L1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of CWF19-like protein 1 (CWF19L1).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of CWF19-like protein 1 (CWF19L1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CWF19-like protein 1 (CWF19L1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of CWF19-like protein 1 (CWF19L1).	[10]

References

• [1] Homozygous splice mutation in CWF19L1 in a Turkish family with recessive ataxia syndrome. Neurology. 2014 Dec 2;83(23):2175-82. doi: 10.1212/WNL.0000000000001053. Epub 2014 Oct 31.
• [2] Exome sequencing reveals a novel CWF19L1 mutation associated with intellectual disability and cerebellar atrophy.Am J Med Genet A. 2016 Jun;170(6):1502-9. doi: 10.1002/ajmg.a.37632. Epub 2016 Mar 26.
• [3] The ERLIN1-CHUK-CWF19L1 gene cluster influences liver fat deposition and hepatic inflammation in the NHLBI Family Heart Study.Atherosclerosis. 2013 May;228(1):175-80. doi: 10.1016/j.atherosclerosis.2013.01.038. Epub 2013 Feb 18.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.