Details of Drug Off-Target (DOT)

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

• DOT Name: Ameloblastin (AMBN)
• Gene Name: AMBN
• Related Disease:
  Amelogenesis imperfecta
  Amelogenesis imperfecta type 1B
  Amelogenesis imperfecta type 1F
  Bone osteosarcoma
  Exanthem
  Osteosarcoma
  Amelogenesis imperfecta type 1
  Dental caries
  Neoplasm
• UniProt ID: AMBN_HUMAN
• Pfam ID: PF05111
• Sequence:
  MSASKIPLFKMKDLILILCLLEMSFAVPFFPQQSGTPGMASLSLETMRQLGSLQRLNTLS
  QYSRYGFGKSFNSLWMHGLLPPHSSLPWMRPREHETQQYEYSLPVHPPPLPSQPSLKPQQ
  PGLKPFLQSAAATTNQATALKEALQPPIHLGHLPLQEGELPLVQQQVAPSDKPPKPELPG
  VDFADPQGPSLPGMDFPDPQGPSLPGLDFADPQGSTIFQIARLISHGPMPQNKQSPLYPG
  MLYVPFGANQLNAPARLGIMSSEEVAGGREDPMAYGAMFPGFGGMRPGFEGMPHNPAMGG
  DFTLEFDSPVAATKGPENEEGGAQGSPMPEANPDNLENPAFLTELEPAPHAGLLALPKDD
  IPGLPRSPSGKMKGLPSVTPAAADPLMTPELADVYRTYDADMTTSVDFQEEATMDTTMAP
  NSLQTSMPGNKAQEPEMMHDAWHFQEP
• Function: Involved in the mineralization and structural organization of enamel.
• Tissue Specificity: Ameloblast-specific. Located at the Tomes processes of secretory ameloblasts and in the sheath space between rod-interrod enamel.
• 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amelogenesis imperfecta	DISGYR9E	Strong	Genetic Variation	[1]
Amelogenesis imperfecta type 1B	DISWPUI8	Strong	Biomarker	[2]
Amelogenesis imperfecta type 1F	DIS4K44C	Strong	Autosomal recessive	[3]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[4]
Exanthem	DISAFOQN	Strong	Biomarker	[5]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Amelogenesis imperfecta type 1	DISVEG5A	Supportive	Autosomal dominant	[6]
Dental caries	DISRBCMD	Limited	Biomarker	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Ameloblastin (AMBN).	[8]

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 increases the methylation of Ameloblastin (AMBN).	[9]

References

• [1] AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity.Mol Genet Genomic Med. 2019 Sep;7(9):e929. doi: 10.1002/mgg3.929. Epub 2019 Aug 11.
• [2] Human ameloblastin gene: genomic organization and mutation analysis in amelogenesis imperfecta patients.Eur J Oral Sci. 2001 Feb;109(1):8-13. doi: 10.1034/j.1600-0722.2001.00979.x.
• [3] Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts. J Cell Biol. 2004 Dec 6;167(5):973-83. doi: 10.1083/jcb.200409077.
• [4] Ameloblastin induces tumor suppressive phenotype and enhances chemosensitivity to doxorubicin via Src-Stat3 inactivation in osteosarcoma.Sci Rep. 2017 Jan 5;7:40187. doi: 10.1038/srep40187.
• [5] Genetic analysis of familial non-syndromic primary failure of eruption.Orthod Craniofac Res. 2009 May;12(2):74-81. doi: 10.1111/j.1601-6343.2009.01440.x.
• [6] Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta. Hum Mol Genet. 2014 Oct 15;23(20):5317-24. doi: 10.1093/hmg/ddu247. Epub 2014 May 23.
• [7] Calcium and magnesium levels in primary tooth enamel and genetic variation in enamel formation genes.Pediatr Dent. 2014 Sep-Oct;36(5):384-8.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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.