Details of Drug Off-Target (DOT)

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

• DOT Name: Protocadherin gamma-A4 (PCDHGA4)
• Synonyms: PCDH-gamma-A4
• Gene Name: PCDHGA4
• Related Disease:
  Atrial septal defect
  Type-1/2 diabetes
• UniProt ID: PCDG4_HUMAN
• Pfam ID: PF00028 ; PF08266 ; PF16492 ; PF15974
• Sequence:
  MHFILDPEDPGAPQASTEGKPKHRRLRGGVVMAAPPARPDHTRLLQICLLLGVLVEIRAE
  QILYSVFEEQEEGSVVGNIAKDLGLAPRELAERGVRIVSRGRTQLFALNPRSGTLVTAGR
  IDREELCDRSPNCVTNLEILLEDTVKILRVEVEIIDVNDNPPSFGTEQREIKVAENENPG
  ARFPLPEAFDPDVGVNSLQGYQLNSNGYFSLDVQSGADGIKYPELVLERALDREEEAVHH
  LVLTAFDGGDPVRSGTARILIILVDTNDNAPVFTQPEYHVSVRENVPVGTRLLTVKATDP
  DEGANGDVTYSFRKVRDKISQLFQLNSLSGDITILGGLDYEDSGFYDIDVEAHDGPGLRA
  RSKVLVTVLDENDNAPEVTVTSLTSSVQESSSPGTVIALFNVHDSDSGGNGLVTCSIPDN
  LPFTLEKTYGNYYRLLTHRTLDREEVSEYNITVTATDQGTPPLSTETHISLQVMDINDNP
  PTFPHASYSAYIPENNPRGASILSMTAQDPDSGDNARITYSLAEDTFQGAPLSSYVSINS
  NTGILYALCSFDYEQFRDLQLLMTASDSGDPPLSSNVSLSLFVLDQNDNVPEILYPTFPT
  DGSTGVELAPRSADSGYLVTKVVAVDRDSGQNAWLSYSLLKSSEPGLFAVGLHTGEVRTA
  RALLDRDALKQRLVVVVQDHGQPPLSATVTLTVAVADSIPDVLADLGSLKPSADPDDSGL
  TLYLVVAVAAVSCVFLAFVTVLLALKLRRWHKSRLLHAEGSRLAGVPASHFVGVDGVRAF
  LQTYSHEVSLTADSRKSHLIFSQPSYADTLISRESCEKSEPLLITQDLLETKGDPNLQQA
  PPNTDWRFSQAQRPGTSGSQNGDDTGTWPNNQFDTEMLQAMILASASEAADGSSTLGGGA
  GTMGLSARYGPQFTLQHVPDYRQNVYIPGSNATLTNAAGKRDGKAPAGGNGNKKKSGKKE
  KK
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial septal defect	DISJT76B	Limited	Genetic Variation	[1]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protocadherin gamma-A4 (PCDHGA4).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protocadherin gamma-A4 (PCDHGA4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protocadherin gamma-A4 (PCDHGA4).	[6]

1 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 Protocadherin gamma-A4 (PCDHGA4).	[4]

References

• [1] Identification of Two Mutations in PCDHGA4 and SLFN14 Genes in an Atrial Septal Defect Family.Curr Med Sci. 2018 Dec;38(6):989-996. doi: 10.1007/s11596-018-1974-2. Epub 2018 Dec 7.
• [2] Differential methylation of genes in individuals exposed to maternal diabetes in utero.Diabetologia. 2017 Apr;60(4):645-655. doi: 10.1007/s00125-016-4203-1. Epub 2017 Jan 26.
• [3] 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.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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.