Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3JJI7L)

• DOT Name: Protocadherin gamma-A12 (PCDHGA12)
• Synonyms: PCDH-gamma-A12; Cadherin-21; Fibroblast cadherin-3
• Gene Name: PCDHGA12
• Related Disease:
  Knee osteoarthritis
  Psoriasis
  Age-related macular degeneration
  Neoplasm
  Osteoarthritis
• UniProt ID: PCDGC_HUMAN
• Pfam ID: PF00028 ; PF08266 ; PF16492 ; PF15974
• Sequence:
  MIPARLHRDYKGLVLLGILLGTLWETGCTQIRYSVPEELEKGSRVGDISRDLGLEPRELA
  ERGVRIIPRGRTQLFALNPRSGSLVTAGRIDREELCMGAIKCQLNLDILMEDKVKIYGVE
  VEVRDINDNAPYFRESELEIKISENAATEMRFPLPHAWDPDIGKNSLQSYELSPNTHFSL
  IVQNGADGSKYPELVLKRALDREEKAAHHLVLTASDGGDPVRTGTARIRVMVLDANDNAP
  AFAQPEYRASVPENLALGTQLLVVNATDPDEGVNAEVRYSFRYVDDKAAQVFKLDCNSGT
  ISTIGELDHEESGFYQMEVQAMDNAGYSARAKVLITVLDVNDNAPEVVLTSLASSVPENS
  PRGTLIALLNVNDQDSEENGQVICFIQGNLPFKLEKSYGNYYSLVTDIVLDREQVPSYNI
  TVTATDRGTPPLSTETHISLNVADTNDNPPVFPQASYSAYIPENNPRGVSLVSVTAHDPD
  CEENAQITYSLAENTIQGASLSSYVSINSDTGVLYALSSFDYEQFRDLQVKVMARDNGHP
  PLSSNVSLSLFVLDQNDNAPEILYPALPTDGSTGVELAPRSAEPGYLVTKVVAVDRDSGQ
  NAWLSYRLLKASEPGLFSVGLHTGEVRTARALLDRDALKQSLVVAVQDHGQPPLSATVTL
  TVAVADSIPQVLADLGSLESPANSETSDLTLYLVVAVAAVSCVFLAFVILLLALRLRRWH
  KSRLLQASGGGLTGAPASHFVGVDGVQAFLQTYSHEVSLTTDSRKSHLIFPQPNYADMLV
  SQESFEKSEPLLLSGDSVFSKDSHGLIEQAPPNTDWRFSQAQRPGTSGSQNGDDTGTWPN
  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
Knee osteoarthritis	DISLSNBJ	Strong	Biomarker	[1]
Psoriasis	DIS59VMN	Strong	Altered Expression	[2]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]
Osteoarthritis	DIS05URM	Limited	Genetic Variation	[5]

2 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-A12 (PCDHGA12).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Protocadherin gamma-A12 (PCDHGA12).	[7]

References

• [1] Relationship between weight loss in obese knee osteoarthritis patients and serum biomarkers of cartilage breakdown: secondary analyses of a randomised trial.Osteoarthritis Cartilage. 2017 Oct;25(10):1641-1646. doi: 10.1016/j.joca.2017.06.009. Epub 2017 Jul 6.
• [2] Overexpressed fibulin-3 contributes to the pathogenesis of psoriasis by promoting angiogenesis.Clin Exp Dermatol. 2019 Jun;44(4):e64-e72. doi: 10.1111/ced.13720. Epub 2018 Aug 26.
• [3] Serum starvation of ARPE-19 changes the cellular distribution of cholesterol and Fibulin3 in patterns reminiscent of age-related macular degeneration.Exp Cell Res. 2017 Dec 15;361(2):333-341. doi: 10.1016/j.yexcr.2017.10.036. Epub 2017 Oct 31.
• [4] Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers.Clin Cancer Res. 2011 Sep 1;17(17):5582-92. doi: 10.1158/1078-0432.CCR-10-2659. Epub 2011 Jul 25.
• [5] Fib3-3 as a Biomarker for Osteoarthritis in a Rat Model with Metabolic Dysregulation.Cartilage. 2019 Jul;10(3):329-334. doi: 10.1177/1947603518754629. Epub 2018 Jan 24.
• [6] 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.
• [7] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.