Details of Drug Off-Target (DOT)

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

• DOT Name: Protocadherin gamma-A3 (PCDHGA3)
• Synonyms: PCDH-gamma-A3
• Gene Name: PCDHGA3
• Related Disease:
  Pineoblastoma
  Stroke
  B-cell neoplasm
  Follicular lymphoma
  Neoplasm
• UniProt ID: PCDG3_HUMAN
• Pfam ID: PF00028 ; PF08266 ; PF16492 ; PF15974
• Sequence:
  MTNCLSFRNGRGLALLCALLGTLCETGSGQIRYSVSEELDKGSFVGNIANDLGLEPRELA
  ERGVRIVSRGRTQLFSLNPQSGSLVTAERIDREELCAQIPLCLVKINILVEDKLKIFEVE
  IEIKDINDNAPNFPTEELEIKIGELTVPGTRFPIKTAFDPDVGINSLQNYKLSPNDYFSL
  AVNSVSEGAKYPELVLERALDREKKEIHQLVLVASDGGDPVHSGNLHIQVIVLDANDNPP
  MFTQPEYRVSVWENVPVGTRLLTVNATDPDEGFNAQVSYILDKMPGKIAEIFHLNSVSGE
  VSILKSLDYEDAMFYEIKIEAQDGPGLLSRAKILVTVLDVNDNAPEITITSLTSSVPEEG
  TVGREIALIDVHDRDSGQNGQVEVFVLGNLPFKLEKSIDQYYRLVTATSLDREQISEYNI
  SLRASDGGSPPLSTETHITLHVIDINDNPPTFPHLSYSAYIPENNPRGASIFSVTAQDPD
  SNNNARITYALTEDTLQGAPLSSFVSINSNTGVLYALRSFDYEQFRDLKLLVTASDSGNP
  PLSSNVSLNLFVLDQNDNAPEILYPALPTDGSTGVELAPRSAEPGYLVTKVVAVDRDSGQ
  NAWLSYRLLKASEPGLFSVGLHTGEVRTARALLDRDALKQSLVVAVQDHGQPPLSATVTL
  TVAVADRIPDILADLGSLEPSAKPNDSDLTLYLVVAVAAVSCVFLAFVIVLLALRLRRWH
  KSRLLQASGGGLASTPGSHFVGADGVRAFLQTYSHEVSLTADSRKSHLIFPQPNYADTLI
  SQESCEKSEPLLITQDLLEMKGDSNLLQQAPPNTDWRFSQAQRPGTSGSQNGDDTGTWPN
  NQFDTEMLQAMILASASEAADGSSTLGGGAGTMGLSARYGPQFTLQHVPDYRQNVYIPGS
  NATLTNAAGKRDGKAPAGGNGNKKKSGKKEKK
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pineoblastoma	DISQK8F3	Strong	Biomarker	[1]
Stroke	DISX6UHX	moderate	Altered Expression	[2]
B-cell neoplasm	DISVY326	Disputed	Altered Expression	[3]
Follicular lymphoma	DISVEUR6	Disputed	Biomarker	[3]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[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-A3 (PCDHGA3).	[4]

3 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-A3 (PCDHGA3).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protocadherin gamma-A3 (PCDHGA3).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Protocadherin gamma-A3 (PCDHGA3).	[7]

References

• [1] Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma.Neuro Oncol. 2011 Aug;13(8):866-79. doi: 10.1093/neuonc/nor070.
• [2] New Cell Adhesion Molecules in Human Ischemic Cardiomyopathy. PCDHGA3 Implications in Decreased Stroke Volume and Ventricular Dysfunction.PLoS One. 2016 Jul 29;11(7):e0160168. doi: 10.1371/journal.pone.0160168. eCollection 2016.
• [3] Protocadherin A3 is expressed in follicular lymphoma irrespective of BCL2 status and is associated with tumor cell growth.Mol Med Rep. 2016 Nov;14(5):4622-4628. doi: 10.3892/mmr.2016.5808. Epub 2016 Oct 5.
• [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] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.