Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ0DNZI)

• DOT Name: Protein Wnt-10a
• Gene Name: WNT10A
• Related Disease:
  Ectodermal dysplasia WNT10A related
  Odonto-onycho-dermal dysplasia
  Tooth agenesis, selective, 4
  Autosomal recessive hypohidrotic ectodermal dysplasia
  SchC6pf-Schulz-Passarge syndrome
  Tooth agenesis
• UniProt ID: WN10A_HUMAN
• Pfam ID: PF00110
• Sequence:
  MGSAHPRPWLRLRPQPQPRPALWVLLFFLLLLAAAMPRSAPNDILDLRLPPEPVLNANTV
  CLTLPGLSRRQMEVCVRHPDVAASAIQGIQIAIHECQHQFRDQRWNCSSLETRNKIPYES
  PIFSRGFRESAFAYAIAAAGVVHAVSNACALGKLKACGCDASRRGDEEAFRRKLHRLQLD
  ALQRGKGLSHGVPEHPALPTASPGLQDSWEWGGCSPDMGFGERFSKDFLDSREPHRDIHA
  RMRLHNNRVGRQAVMENMRRKCKCHGTSGSCQLKTCWQVTPEFRTVGALLRSRFHRATLI
  RPHNRNGGQLEPGPAGAPSPAPGAPGPRRRASPADLVYFEKSPDFCEREPRLDSAGTVGR
  LCNKSSAGSDGCGSMCCGRGHNILRQTRSERCHCRFHWCCFVVCEECRITEWVSVCK
• Function: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway. Plays a role in normal ectoderm development. Required for normal tooth development. Required for normal postnatal development and maintenance of tongue papillae and sweat ducts. Required for normal proliferation of basal cells in tongue filiform papillae, plantar epithelium and sweat ducts. Required for normal expression of keratins in tongue papillae. Required for normal expression of KRT9 in foot plant epithelium. Required for normal hair follicle function.
• KEGG Pathway:
  mTOR sig.ling pathway (hsa04150)
  Wnt sig.ling pathway (hsa04310)
  Hippo sig.ling pathway (hsa04390)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Melanogenesis (hsa04916)
  Cushing syndrome (hsa04934)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Basal cell carcinoma (hsa05217)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Class B/2 (Secretin family receptors) (R-HSA-373080)
  WNT ligand biogenesis and trafficking (R-HSA-3238698)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ectodermal dysplasia WNT10A related	DIS7C7EV	Definitive	Semidominant	[1]
Odonto-onycho-dermal dysplasia	DISUYF88	Strong	Autosomal recessive	[2]
Tooth agenesis, selective, 4	DISR4ZRW	Strong	Autosomal dominant	[2]
Autosomal recessive hypohidrotic ectodermal dysplasia	DISGAO5V	Supportive	Autosomal recessive	[3]
SchC6pf-Schulz-Passarge syndrome	DIS3OZ1S	Supportive	Autosomal dominant	[4]
Tooth agenesis	DIS1PWC7	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein Wnt-10a.	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein Wnt-10a.	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein Wnt-10a.	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Protein Wnt-10a.	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein Wnt-10a.	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Protein Wnt-10a.	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein Wnt-10a.	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein Wnt-10a.	[13]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Protein Wnt-10a.	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Protein Wnt-10a.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein Wnt-10a.	[11]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am J Hum Genet. 2007 Oct;81(4):821-8. doi: 10.1086/520064. Epub 2007 Aug 9.
• [3] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [4] WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am J Hum Genet. 2009 Jul;85(1):97-105. doi: 10.1016/j.ajhg.2009.06.001. Epub 2009 Jun 25.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013 Feb;27(1):37-48. doi: 10.1007/s10557-012-6427-8.
• [11] 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.
• [12] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway. Cancer Prev Res (Phila). 2009 Nov;2(11):942-50. doi: 10.1158/1940-6207.CAPR-08-0232. Epub 2009 Oct 27.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.