Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0UJQ4O)

• DOT Name: C-type lectin domain family 14 member A (CLEC14A)
• Synonyms: Epidermal growth factor receptor 5; EGFR-5
• Gene Name: CLEC14A
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Epithelial ovarian cancer
  IgA nephropathy
  Lung adenocarcinoma
  Pancreatic cancer
  Melanoma
• UniProt ID: CLC14_HUMAN
• Sequence:
  MRPAFALCLLWQALWPGPGGGEHPTADRAGCSASGACYSLHHATMKRQAAEEACILRGGA
  LSTVRAGAELRAVLALLRAGPGPGGGSKDLLFWVALERRRSHCTLENEPLRGFSWLSSDP
  GGLESDTLQWVEEPQRSCTARRCAVLQATGGVEPAGWKEMRCHLRANGYLCKYQFEVLCP
  APRPGAASNLSYRAPFQLHSAALDFSPPGTEVSALCRGQLPISVTCIADEIGARWDKLSG
  DVLCPCPGRYLRAGKCAELPNCLDDLGGFACECATGFELGKDGRSCVTSGEGQPTLGGTG
  VPTRRPPATATSPVPQRTWPIRVDEKLGETPLVPEQDNSVTSIPEIPRWGSQSTMSTLQM
  SLQAESKATITPSGSVISKFNSTTSSATPQAFDSSSAVVFIFVSTAVVVLVILTMTVLGL
  VKLCFHESPSSQPRKESMGPPGLESDPEPAALGSSSAHCTNNGVKVGDCDLRDRAEGALL
  AESPLGSSDA

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[4]
Lung adenocarcinoma	DISD51WR	Strong	Posttranslational Modification	[5]
Pancreatic cancer	DISJC981	Strong	Biomarker	[6]
Melanoma	DIS1RRCY	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of C-type lectin domain family 14 member A (CLEC14A).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-type lectin domain family 14 member A (CLEC14A).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of C-type lectin domain family 14 member A (CLEC14A).	[10]

References

• [1] Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer.Angiogenesis. 2019 Feb;22(1):117-131. doi: 10.1007/s10456-018-9642-5. Epub 2018 Aug 21.
• [2] Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling.PLoS One. 2008 Apr 30;3(4):e2079. doi: 10.1371/journal.pone.0002079.
• [3] Expression of a novel endothelial marker, C-type lectin 14A, in epithelial ovarian cancer and its prognostic significance.Int J Clin Oncol. 2017 Feb;22(1):107-117. doi: 10.1007/s10147-016-1033-6. Epub 2016 Aug 27.
• [4] A candidate gene approach to genetic contributors to the development of IgA nephropathy.Nephrol Dial Transplant. 2012 Mar;27(3):1020-30. doi: 10.1093/ndt/gfr369. Epub 2011 Jul 7.
• [5] Methylation of CLEC14A is associated with its expression and lung adenocarcinoma progression.J Cell Physiol. 2019 Mar;234(3):2954-2962. doi: 10.1002/jcp.27112. Epub 2018 Sep 7.
• [6] Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface.Oncogene. 2017 Nov 2;36(44):6097-6108. doi: 10.1038/onc.2017.214. Epub 2017 Jul 3.
• [7] MIG6 Is MEK Regulated and Affects EGF-Induced Migration in Mutant NRAS Melanoma.J Invest Dermatol. 2016 Feb;136(2):453-463. doi: 10.1016/j.jid.2015.11.012. Epub 2015 Nov 20.
• [8] 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.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.