Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH31KJO)

• DOT Name: Cadherin-19 (CDH19)
• Gene Name: CDH19
• Related Disease:
  Head and neck cancer
  Head and neck carcinoma
  Neoplasm
  Adult glioblastoma
  Glioblastoma multiforme
• UniProt ID: CAD19_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MNCYLLLRFMLGIPLLWPCLGATENSQTKKVKQPVRSHLRVKRGWVWNQFFVPEEMNTTS
  HHIGQLRSDLDNGNNSFQYKLLGAGAGSTFIIDERTGDIYAIQKLDREERSLYILRAQVI
  DIATGRAVEPESEFVIKVSDINDNEPKFLDEPYEAIVPEMSPEGTLVIQVTASDADDPSS
  GNNARLLYSLLQGQPYFSVEPTTGVIRISSKMDRELQDEYWVIIQAKDMIGQPGALSGTT
  SVLIKLSDVNDNKPIFKESLYRLTVSESAPTGTSIGTIMAYDNDIGENAEMDYSIEEDDS
  QTFDIITNHETQEGIVILKKKVDFEHQNHYGIRAKVKNHHVPEQLMKYHTEASTTFIKIQ
  VEDVDEPPLFLLPYYVFEVFEETPQGSFVGVVSATDPDNRKSPIRYSITRSKVFNINDNG
  TITTSNSLDREISAWYNLSITATEKYNIEQISSIPLYVQVLNINDHAPEFSQYYETYVCE
  NAGSGQVIQTISAVDRDESIEEHHFYFNLSVEDTNNSSFTIIDNQDNTAVILTNRTGFNL
  QEEPVFYISILIADNGIPSLTSTNTLTIHVCDCGDSGSTQTCQYQELVLSMGFKTEVIIA
  ILICIMIIFGFIFLTLGLKQRRKQILFPEKSEDFRENIFQYDDEGGGEEDTEAFDIAELR
  SSTIMRERKTRKTTSAEIRSLYRQSLQVGPDSAIFRKFILEKLEEANTDPCAPPFDSLQT
  YAFEGTGSLAGSLSSLESAVSDQDESYDYLNELGPRFKRLACMFGSAVQSNN
• Function: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
• Tissue Specificity: Expressed in many tissues, with the exception of uterus.
• Reactome Pathway: Regulation of CDH19 Expression and Function (R-HSA-9764302)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head and neck cancer	DISBPSQZ	Definitive	Altered Expression	[1]
Head and neck carcinoma	DISOU1DS	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[3]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cadherin-19 (CDH19).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cadherin-19 (CDH19).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cadherin-19 (CDH19).	[7]

2 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 Cadherin-19 (CDH19).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cadherin-19 (CDH19).	[8]

References

• [1] Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma.Oncogene. 2002 Jul 25;21(32):5016-23. doi: 10.1038/sj.onc.1205626.
• [2] Genomic profile in gestational and non-gestational choriocarcinomas.Placenta. 2017 Feb;50:8-15. doi: 10.1016/j.placenta.2016.12.009. Epub 2016 Dec 7.
• [3] Myelin-forming cell-specific cadherin-19 is a marker for minimally infiltrative glioblastoma stem-like cells.J Neurosurg. 2015 Jan;122(1):69-77. doi: 10.3171/2014.9.JNS132373.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] 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.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.