Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIN26MM)

DOT Name Amelogenin, X isoform (AMELX)
Gene Name AMELX
Related Disease
Asthma ( )
Adenocarcinoma ( )
Advanced cancer ( )
Alpha-1 antitrypsin deficiency ( )
Amelogenesis imperfecta ( )
Amelogenesis imperfecta type 1E ( )
Atopic dermatitis ( )
Autoimmune hepatitis ( )
Chronic kidney disease ( )
Coeliac disease ( )
Colorectal carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Euthyroid goiter ( )
Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors ( )
Hyperparathyroidism ( )
Hypocalcemia ( )
Nasopharyngitis ( )
Non-small-cell lung cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Schizophrenia ( )
Systemic lupus erythematosus ( )
Timothy syndrome ( )
Tourette syndrome ( )
Tuberous sclerosis ( )
Turner syndrome ( )
Wilson disease ( )
Acute myelogenous leukaemia ( )
Breast cancer ( )
Breast carcinoma ( )
Homozygous familial hypercholesterolemia ( )
Secondary hyperparathyroidism ( )
Amelogenesis imperfecta type 2 ( )
Glioblastoma multiforme ( )
Migraine disorder ( )
Adult lymphoma ( )
Arthritis ( )
Lymphoma ( )
Pediatric lymphoma ( )
UniProt ID
AMELX_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF02948
Sequence
MGTWILFACLLGAAFAMPLPPHPGHPGYINFSYEVLTPLKWYQSIRPPYPSYGYEPMGGW
LHHQIIPVLSQQHPPTHTLQPHHHIPVVPAQQPVIPQQPMMPVPGQHSMTPIQHHQPNLP
PPAQQPYQPQPVQPQPHQPMQPQPPVHPMQPLPPQPPLPPMFPMQPLPPMLPDLTLEAWP
STDKTKREEVD
Function
Plays a role in biomineralization. Seems to regulate the formation of crystallites during the secretory stage of tooth enamel development. Thought to play a major role in the structural organization and mineralization of developing 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

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Asthma DISW9QNS Definitive Biomarker [1]
Adenocarcinoma DIS3IHTY Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Alpha-1 antitrypsin deficiency DISQKEHW Strong Biomarker [4]
Amelogenesis imperfecta DISGYR9E Strong Genetic Variation [5]
Amelogenesis imperfecta type 1E DISQK3F9 Strong X-linked [6]
Atopic dermatitis DISTCP41 Strong Biomarker [7]
Autoimmune hepatitis DISOX03Q Strong Biomarker [4]
Chronic kidney disease DISW82R7 Strong Biomarker [8]
Coeliac disease DISIY60C Strong Biomarker [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Endometrial cancer DISW0LMR Strong Altered Expression [11]
Endometrial carcinoma DISXR5CY Strong Altered Expression [11]
Euthyroid goiter DISLRPYJ Strong Biomarker [12]
Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors DISVJILV Strong Biomarker [12]
Hyperparathyroidism DIS4FVAT Strong Biomarker [13]
Hypocalcemia DISTCK2W Strong Biomarker [14]
Nasopharyngitis DISVLL0V Strong Genetic Variation [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [16]
Prostate cancer DISF190Y Strong Altered Expression [17]
Prostate carcinoma DISMJPLE Strong Altered Expression [17]
Schizophrenia DISSRV2N Strong Biomarker [18]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [19]
Timothy syndrome DISBXBZP Strong Biomarker [20]
Tourette syndrome DISX9D54 Strong Biomarker [20]
Tuberous sclerosis DISEMUGZ Strong Biomarker [20]
Turner syndrome DIS2035C Strong Genetic Variation [20]
Wilson disease DISVS9H7 Strong Biomarker [4]
Acute myelogenous leukaemia DISCSPTN moderate Biomarker [21]
Breast cancer DIS7DPX1 moderate Altered Expression [22]
Breast carcinoma DIS2UE88 moderate Altered Expression [22]
Homozygous familial hypercholesterolemia DISRCNCF moderate Genetic Variation [23]
Secondary hyperparathyroidism DISZX24B moderate Biomarker [8]
Amelogenesis imperfecta type 2 DISX8NN4 Supportive Autosomal recessive [24]
Glioblastoma multiforme DISK8246 Disputed Biomarker [25]
Migraine disorder DISFCQTG Disputed Biomarker [26]
Adult lymphoma DISK8IZR Limited Biomarker [27]
Arthritis DIST1YEL Limited Biomarker [28]
Lymphoma DISN6V4S Limited Biomarker [27]
Pediatric lymphoma DIS51BK2 Limited Biomarker [27]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Amelogenin, X isoform (AMELX). [29]
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References

1 Pharmacokinetics, Safety, and Tolerability of Tezepelumab (AMG 157) in Healthy and Atopic Dermatitis Adult Subjects.Clin Pharmacol Ther. 2019 Aug;106(2):441-449. doi: 10.1002/cpt.1401. Epub 2019 Mar 23.
2 (89)Zr-labeled Bispecific T-cell Engager AMG 211 PET Shows AMG 211 Accumulation in CD3-rich Tissues and Clear, Heterogeneous Tumor Uptake.Clin Cancer Res. 2019 Jun 15;25(12):3517-3527. doi: 10.1158/1078-0432.CCR-18-2918. Epub 2019 Feb 11.
3 In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models.Mol Cancer Ther. 2016 Jul;15(7):1568-79. doi: 10.1158/1535-7163.MCT-15-0871. Epub 2016 Apr 19.
4 Tryptophan-kynurenine profile in pediatric autoimmune hepatitis.Immunol Res. 2019 Feb;67(1):39-47. doi: 10.1007/s12026-019-9068-1.
5 Protocol GenoDENT: Implementation of a New NGS Panel for Molecular Diagnosis of Genetic Disorders with Orodental Involvement.Methods Mol Biol. 2019;1922:407-452. doi: 10.1007/978-1-4939-9012-2_36.
6 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
7 Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial.J Am Acad Dermatol. 2019 Apr;80(4):1013-1021. doi: 10.1016/j.jaad.2018.11.059. Epub 2018 Dec 12.
8 Drug disposition model of radiolabeled etelcalcetide in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis.J Pharmacokinet Pharmacodyn. 2017 Feb;44(1):43-53. doi: 10.1007/s10928-016-9503-z. Epub 2017 Jan 6.
9 Safety and efficacy of AMG 714 in adults with coeliac disease exposed to gluten challenge: a phase 2a, randomised, double-blind, placebo-controlled study.Lancet Gastroenterol Hepatol. 2019 Dec;4(12):948-959. doi: 10.1016/S2468-1253(19)30264-X. Epub 2019 Sep 4.
10 CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas.MAbs. 2014;6(6):1571-84. doi: 10.4161/19420862.2014.975660.
11 AMG 479, a novel IGF-1-R antibody, inhibits endometrial cancer cell proliferation through disruption of the PI3K/Akt and MAPK pathways.Reprod Sci. 2011 Sep;18(9):832-41. doi: 10.1177/1933719111398501.
12 Radioiodine therapy of benign thyroid-disorders.Nuklearmedizin. 2017;56(5):171-176. doi: 10.3413/Nukmed-0875-17-01. Epub 2018 Jan 4.
13 Recent advances in nephrology: highlights from the 35th annual meeting of the American society of nephrology.Drugs Today (Barc). 2002 Dec;38(12):797-805.
14 Changes in amelogenesis in the rat incisor following short-term hypocalcaemia.Arch Oral Biol. 2005 Feb;50(2):185-8. doi: 10.1016/j.archoralbio.2004.11.022.
15 Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study.Lancet Gastroenterol Hepatol. 2019 Dec;4(12):960-970. doi: 10.1016/S2468-1253(19)30265-1. Epub 2019 Sep 4.
16 Dueling KRAS(G12C) Inhibitors Achieve Responses.Cancer Discov. 2020 Jan;10(1):10. doi: 10.1158/2159-8290.CD-ND2019-012. Epub 2019 Dec 10.
17 A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors. Oncotarget. 2015 Jul 30;6(21):18693-706.
18 Efficacy and safety of the glycine transporter type-1 inhibitor AMG 747 for the treatment of negative symptoms associated with schizophrenia.Schizophr Res. 2017 Apr;182:90-97. doi: 10.1016/j.schres.2016.10.027. Epub 2016 Oct 24.
19 Blockade of interferon- normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus.Arthritis Rheumatol. 2015 Oct;67(10):2713-22. doi: 10.1002/art.39248.
20 Refined quantitative fluorescent PCR of Y-chromosome DNA sequences mosaics in Turner's syndrome patients--alternative to real-time PCR.J Biochem Biophys Methods. 2004 Aug 31;60(2):151-62. doi: 10.1016/j.jbbm.2004.05.004.
21 Dual Targeting of Aurora Kinases with AMG 900 Exhibits Potent Preclinical Activity Against Acute Myeloid Leukemia with Distinct Post-Mitotic Outcomes.Mol Cancer Ther. 2018 Dec;17(12):2575-2585. doi: 10.1158/1535-7163.MCT-18-0186. Epub 2018 Sep 28.
22 AMG 900, pan-Aurora kinase inhibitor, preferentially inhibits the proliferation of breast cancer cell lines with dysfunctional p53.Breast Cancer Res Treat. 2013 Oct;141(3):397-408. doi: 10.1007/s10549-013-2702-z. Epub 2013 Oct 5.
23 Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia.Circulation. 2013 Nov 5;128(19):2113-20. doi: 10.1161/CIRCULATIONAHA.113.004678. Epub 2013 Sep 6.
24 Amelogenesis imperfecta in two families with defined AMELX deletions in ARHGAP6. PLoS One. 2012;7(12):e52052. doi: 10.1371/journal.pone.0052052. Epub 2012 Dec 14.
25 Safety, tolerability, and pharmacokinetics of anti-EGFRvIII antibody-drug conjugate AMG 595 in patients with recurrent malignant glioma expressing EGFRvIII.Cancer Chemother Pharmacol. 2019 Aug;84(2):327-336. doi: 10.1007/s00280-019-03879-2. Epub 2019 Jun 1.
26 Erenumab (AMG 334), a monoclonal antagonist antibody against the canonical CGRP receptor, does not impair vasodilatory or contractile responses to other vasoactive agents in human isolated cranial arteries.Cephalalgia. 2019 Dec;39(14):1745-1752. doi: 10.1177/0333102419867282. Epub 2019 Jul 31.
27 Single and combined BTK and PI3K inhibition with acalabrutinib and ACP-319 in pre-clinical models of aggressive lymphomas.Br J Haematol. 2019 Dec;187(5):595-601. doi: 10.1111/bjh.16118. Epub 2019 Jul 29.
28 Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis: effect of age, gender, and genetic background.J Clin Gastroenterol. 2008 Mar;42(3):300-5. doi: 10.1097/MCG.0b013e31802dbdfc.
29 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.