Details of Drug Off-Target (DOT)

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

• DOT Name: Protocadherin alpha-9 (PCDHA9)
• Synonyms: PCDH-alpha-9
• Gene Name: PCDHA9
• Related Disease:
  Heart valve disorder
  Hirschsprung disease
  Hypoplastic left heart syndrome
• UniProt ID: PCDA9_HUMAN
• Pfam ID: PF00028 ; PF08266 ; PF15974
• Sequence:
  MLYSSRGDPEGQPLLLSLLILAMWVVGSGQLHYSVPEEAEHGTFVGRIAQDLGLELAELV
  PRLFQLDSKGRGDLLEVNLQNGILFVNSRIDREELCGRSAECSIHLEVIVDRPLQVFHVD
  VEVKDINDNPPVFPATQKNLFIAESRPLDSRFPLEGASDADIGENALLTYRLSPNEYFFL
  DVPTSNQQVKPLGLVLRKLLDREETPELHLLLTATDGGKPELTGTVQLLITVLDNNDNAP
  VFDRTLYTVKLPENVSIGTLVIHPNASDLDEGLNGDIIYSFSSDVSPDIKSKFHMDPLSG
  AITVIGHMDFEESRAHKIPVEAVDKGFPPLAGHCTLLVEVVDVNDNAPQLTIKTLSVPVK
  EDAQLGTVIALISVIDLDADANGQVTCSLTPHVPFKLVSTYKNYYSLVLDRALDRESVSA
  YELVVTARDGGSPSLWATARVSVEVADVNDNAPAFAQSEYTVFVKENNPPGCHIFTVSAR
  DADAQENALVSYSLVERRLGERSLSSYVSVHAESGKVYALQPLDHEELELLQFQVSARDA
  GVPPLGSNVTLQVFVLDENDNAPALLTPRMRGTDGAVSEMVLRSVGAGVVVGKVRAVDAD
  SGYNAWLSYELQPETASASIPFRVGLYTGEISTTRALDETDAPRQRLLVLVKDHGEPALT
  ATATVLVSLVESGQAPKSSSRASVGATGPEVTLVDVNVYLIIAICAVSSLLVLTLLLYTV
  LRCSAMPTEGECAPGKPTLVCSSAVGSWSYSQQRRQRVCSGEGKQKTDLMAFSPGLSPCA
  GSTERTGEPSASSDSTGKPRQPNPDWRYSASLRAGMHSSVHLEEAGILRAGPGGPDQQWP
  TVSSATPEPEAGEVSPPVGAGVNSNSWTFKYGPGNPKQSGPGELPDKFIIPGSPAIISIR
  QEPTNSQIDKSDFITFGKKEETKKKKKKKKGNKTQEKKEKGNSTTDNSDQ
• Function: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Heart valve disorder	DIS84O7T	moderate	Biomarker	[1]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[2]
Hypoplastic left heart syndrome	DISSLFZ4	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protocadherin alpha-9 (PCDHA9).	[3]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Protocadherin alpha-9 (PCDHA9).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protocadherin alpha-9 (PCDHA9).	[4]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Protocadherin alpha-9 (PCDHA9).	[5]

References

• [1] The complex genetics of hypoplastic left heart syndrome.Nat Genet. 2017 Jul;49(7):1152-1159. doi: 10.1038/ng.3870. Epub 2017 May 22.
• [2] Identification of two novel PCDHA9 mutations associated with Hirschsprung's disease.Gene. 2018 Jun 5;658:96-104. doi: 10.1016/j.gene.2018.02.054. Epub 2018 Feb 22.
• [3] 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.
• [4] 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.
• [5] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [6] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.