Details of Drug Off-Target (DOT)

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

• DOT Name: Protocadherin gamma-C3 (PCDHGC3)
• Synonyms: PCDH-gamma-C3; Protocadherin-2; Protocadherin-43; PC-43
• Gene Name: PCDHGC3
• Related Disease:
  Adenoma
  Advanced cancer
  Carcinoma
  Neoplasm
  Pheochromocytoma
  Clear cell renal carcinoma
• UniProt ID: PCDGK_HUMAN
• Pfam ID: PF00028 ; PF08266 ; PF16492 ; PF15974
• Sequence:
  MVPEAWRSGLVSTGRVVGVLLLLGALNKASTVIHYEIPEEREKGFAVGNVVANLGLDLGS
  LSARRFRVVSGASRRFFEVNRETGEMFVNDRLDREELCGTLPSCTVTLELVVENPLELFS
  VEVVIQDINDNNPAFPTQEMKLEISEAVAPGTRFPLESAHDPDVGSNSLQTYELSRNEYF
  ALRVQTREDSTKYAELVLERALDREREPSLQLVLTALDGGTPALSASLPIHIKVLDANDN
  APVFNQSLYRARVLEDAPSGTRVVQVLATDLDEGPNGEIIYSFGSHNRAGVRQLFALDLV
  TGMLTIKGRLDFEDTKLHEIYIQAKDKGANPEGAHCKVLVEVVDVNDNAPEITVTSVYSP
  VPEDAPLGTVIALLSVTDLDAGENGLVTCEVPPGLPFSLTSSLKNYFTLKTSADLDRETV
  PEYNLSITARDAGTPSLSALTIVRVQVSDINDNPPQSSQSSYDVYIEENNLPGAPILNLS
  VWDPDAPQNARLSFFLLEQGAETGLVGRYFTINRDNGIVSSLVPLDYEDRREFELTAHIS
  DGGTPVLATNISVNIFVTDRNDNAPQVLYPRPGGSSVEMLPRGTSAGHLVSRVVGWDADA
  GHNAWLSYSLLGSPNQSLFAIGLHTGQISTARPVQDTDSPRQTLTVLIKDNGEPSLSTTA
  TLTVSVTEDSPEARAEFPSGSAPREQKKNLTFYLLLSLILVSVGFVVTVFGVIIFKVYKW
  KQSRDLYRAPVSSLYRTPGPSLHADAVRGGLMSPHLYHQVYLTTDSRRSDPLLKKPGAAS
  PLASRQNTLRSCDPVFYRQVLGAESAPPGQQAPPNTDWRFSQAQRPGTSGSQNGDDTGTW
  PNNQFDTEMLQAMILASASEAADGSSTLGGGAGTMGLSARYGPQFTLQHVPDYRQNVYIP
  GSNATLTNAAGKRDGKAPAGGNGNKKKSGKKEKK
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Posttranslational Modification	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Pheochromocytoma	DIS56IFV	Strong	Posttranslational Modification	[2]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[3]

1 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-C3 (PCDHGC3).	[4]

13 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-C3 (PCDHGC3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protocadherin gamma-C3 (PCDHGC3).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[10]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Protocadherin gamma-C3 (PCDHGC3).	[11]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[9]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Protocadherin gamma-C3 (PCDHGC3).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[15]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Protocadherin gamma-C3 (PCDHGC3).	[16]

References

• [1] Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways.Oncogene. 2012 Oct 4;31(40):4409-19. doi: 10.1038/onc.2011.609. Epub 2012 Jan 16.
• [2] Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations.J Clin Endocrinol Metab. 2019 Nov 1;104(11):5673-5692. doi: 10.1210/jc.2018-01471.
• [3] Key miRNAs and target genes played roles in the development of clear cell renal cell carcinoma.Cancer Biomark. 2018;23(2):279-290. doi: 10.3233/CBM-181558.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [11] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [12] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [16] Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.