Details of Drug Off-Target (DOT)

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

• DOT Name: Claudin-17 (CLDN17)
• Gene Name: CLDN17
• Related Disease:
  Neoplasm
  Alzheimer disease
  Hepatocellular carcinoma
• UniProt ID: CLD17_HUMAN
• Pfam ID: PF00822
• Sequence:
  MAFYPLQIAGLVLGFLGMVGTLATTLLPQWRVSAFVGSNIIVFERLWEGLWMNCIRQARV
  RLQCKFYSSLLALPPALETARALMCVAVALSLIALLIGICGMKQVQCTGSNERAKAYLLG
  TSGVLFILTGIFVLIPVSWTANIIIRDFYNPAIHIGQKRELGAALFLGWASAAVLFIGGG
  LLCGFCCCNRKKQGYRYPVPGYRVPHTDKRRNTTMLSKTSTSYV
• Function: Channel-forming tight junction protein with selectivity for anions, including chloride and bicarbonate, and for solutes smaller than 9 Angstrom in diameter. In the kidney proximal tubule, may be involved in quantitative reabsorption of filtered anions. Does not affect water permeability.
• Tissue Specificity: In the kidney, expressed in the proximal tubule and in the Henle's loop. In the distal convoluted tubule, not expressed in all tubules. Not detected in the collecting duct (at protein level).
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Tight junction (hsa04530)
  Leukocyte transendothelial migration (hsa04670)
  Pathogenic Escherichia coli infection (hsa05130)
  Hepatitis C (hsa05160)
• Reactome Pathway: Tight junction interactions (R-HSA-420029)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Claudin-17 (CLDN17).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Claudin-17 (CLDN17).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Claudin-17 (CLDN17).	[6]

References

• [1] Expression of tight junction molecules in breast carcinomas analysed by array PCR and immunohistochemistry.Pathol Oncol Res. 2012 Jul;18(3):593-606. doi: 10.1007/s12253-011-9481-9. Epub 2011 Dec 23.
• [2] Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals.JAMA Neurol. 2015 Nov;72(11):1313-23. doi: 10.1001/jamaneurol.2015.1700.
• [3] Increased expression of claudin-17 promotes a malignant phenotype in hepatocyte via Tyk2/Stat3 signaling and is associated with poor prognosis in patients with hepatocellular carcinoma.Diagn Pathol. 2018 Sep 15;13(1):72. doi: 10.1186/s13000-018-0749-1.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] 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.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.