Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXAMT4V)

• DOT Name: Amelotin (AMTN)
• Gene Name: AMTN
• Related Disease:
  Squamous cell carcinoma
  Amelogenesis imperfecta
  Amelogenesis imperfecta type 2
  Gingivitis
  Amelogenesis imperfecta, type 3A
  Amelogenesis imperfecta type 3B
• UniProt ID: AMTN_HUMAN
• Pfam ID: PF15757
• Sequence:
  MRSTILLFCLLGSTRSLPQLKPALGLPPTKLAPDQGTLPNQQQSNQVFPSLSLIPLTQML
  TLGPDLHLLNPAAGMTPGTQTHPLTLGGLNVQQQLHPHVLPIFVTQLGAQGTILSSEELP
  QIFTSLIIHSLFPGGILPTSQAGANPDVQDGSLPAGGAGVNPATQGTPAGRLPTPSGTDD
  DFAVTTPAGIQRSTHAIEEATTESANGIQ
• Function: Is a promoter of calcium phosphate mineralization, playing a critical role in the formation of the compact, mineralized, aprismatic enamel surface layer during the maturation stage of amelogenesis.
• Reactome Pathway:
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[1]
Amelogenesis imperfecta	DISGYR9E	moderate	Genetic Variation	[2]
Amelogenesis imperfecta type 2	DISX8NN4	moderate	Biomarker	[3]
Gingivitis	DISC8RMX	moderate	Biomarker	[4]
Amelogenesis imperfecta, type 3A	DISP3OJG	Supportive	Autosomal dominant	[3]
Amelogenesis imperfecta type 3B	DISUYYW8	Limited	Autosomal dominant	[5]

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 Amelotin (AMTN).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Amelotin (AMTN).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Amelotin (AMTN).	[8]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Amelotin (AMTN).	[9]

References

• [1] Differences in the early stage gene expression profiles of lung adenocarcinoma and lung squamous cell carcinoma.Oncol Lett. 2019 Dec;18(6):6572-6582. doi: 10.3892/ol.2019.11013. Epub 2019 Oct 21.
• [2] Examination of rare genetic variants in dental enamel genes: The potential role of next-generation sequencing in primary dental care.Orthod Craniofac Res. 2019 May;22 Suppl 1:49-55. doi: 10.1111/ocr.12266.
• [3] Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta. Hum Mol Genet. 2016 Aug 15;25(16):3578-3587. doi: 10.1093/hmg/ddw203. Epub 2016 Jul 12.
• [4] Transcriptional regulation of amelotin gene by proinflammatory cytokines in gingival fibroblasts.Connect Tissue Res. 2014 Aug;55 Suppl 1:18-20. doi: 10.3109/03008207.2014.923848.
• [5] Enamel Hypomineralization and Structural Defects in Amelotin-deficient Mice. J Dent Res. 2015 May;94(5):697-705. doi: 10.1177/0022034514566214. Epub 2015 Feb 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] 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.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.