Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU17BCI)

DOT Name	AMP deaminase 1 (AMPD1)
Synonyms	EC 3.5.4.6; AMP deaminase isoform M; Myoadenylate deaminase
Gene Name	AMPD1
Related Disease	Glioma ( ) Metabolic disorder ( ) Myocardial infarction ( ) Non-insulin dependent diabetes ( ) Thyroid gland carcinoma ( ) Thyroid gland papillary carcinoma ( ) Type-1 diabetes ( ) Advanced cancer ( ) Astrocytoma ( ) Attention deficit hyperactivity disorder ( ) Autism ( ) B-cell lymphoma ( ) Carcinoma ( ) Classic Hodgkin lymphoma ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Cystic fibrosis ( ) Cytomegalovirus infection ( ) Depression ( ) Dilated cardiomyopathy 1A ( ) Essential hypertension ( ) Fatty liver disease ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Myocardial ischemia ( ) Myopathy due to myoadenylate deaminase deficiency ( ) Neoplasm ( ) Obesity ( ) Prostate cancer ( ) Prostate carcinoma ( ) Rheumatoid arthritis ( ) Small lymphocytic lymphoma ( ) Type-1/2 diabetes ( ) Cardiovascular disease ( ) Glycogen storage disease V ( ) Hutchinson-Gilford progeria syndrome ( ) Myopathy ( ) Renal cell carcinoma ( ) Adenosine monophosphate deaminase deficiency ( ) Adenocarcinoma ( ) Barrett esophagus ( ) Breast cancer ( ) Breast carcinoma ( ) Cardiac failure ( ) Congestive heart failure ( ) Esophageal adenocarcinoma ( ) Esophageal cancer ( ) Hyperglycemia ( )
UniProt ID	AMPD1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.5.4.6
Pfam ID	PF19326
Sequence	MPLFKLPAEEKQIDDAMRNFAEKVFASEVKDEGGRQEISPFDVDEICPISHHEMQAHIFH LETLSTSTEARRKKRFQGRKTVNLSIPLSETSSTKLSHIDEYISSSPTYQTVPDFQRVQI TGDYASGVTVEDFEIVCKGLYRALCIREKYMQKSFQRFPKTPSKYLRNIDGEAWVANESF YPVFTPPVKKGEDPFRTDNLPENLGYHLKMKDGVVYVYPNEAAVSKDEPKPLPYPNLDTF LDDMNFLLALIAQGPVKTYTHRRLKFLSSKFQVHQMLNEMDELKELKNNPHRDFYNCRKV DTHIHAAACMNQKHLLRFIKKSYQIDADRVVYSTKEKNLTLKELFAKLKMHPYDLTVDSL DVHAGRQTFQRFDKFNDKYNPVGASELRDLYLKTDNYINGEYFATIIKEVGADLVEAKYQ HAEPRLSIYGRSPDEWSKLSSWFVCNRIHCPNMTWMIQVPRIYDVFRSKNFLPHFGKMLE NIFMPVFEATINPQADPELSVFLKHITGFDSVDDESKHSGHMFSSKSPKPQEWTLEKNPS YTYYAYYMYANIMVLNSLRKERGMNTFLFRPHCGEAGALTHLMTAFMIADDISHGLNLKK SPVLQYLFFLAQIPIAMSPLSNNSLFLEYAKNPFLDFLQKGLMISLSTDDPMQFHFTKEP LMEEYAIAAQVFKLSTCDMCEVARNSVLQCGISHEEKVKFLGDNYLEEGPAGNDIRRTNV AQIRMAYRYETWCYELNLIAEGLKSTE
Function	AMP deaminase plays a critical role in energy metabolism.
KEGG Pathway	Purine metabolism (hsa00230 ) Metabolic pathways (hsa01100 ) Nucleotide metabolism (hsa01232 ) Cytoskeleton in muscle cells (hsa04820 )
Reactome Pathway	Purine salvage (R-HSA-74217 )

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Metabolic disorder	DIS71G5H	Definitive	Genetic Variation	[2]
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[3]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[4]
Thyroid gland carcinoma	DISMNGZ0	Definitive	Altered Expression	[5]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[5]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Astrocytoma	DISL3V18	Strong	Biomarker	[7]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[8]
Autism	DISV4V1Z	Strong	Genetic Variation	[9]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[10]
Carcinoma	DISH9F1N	Strong	Biomarker	[11]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[12]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[13]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[14]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[15]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[16]
Depression	DIS3XJ69	Strong	Genetic Variation	[17]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[18]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[19]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[20]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[21]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[22]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[23]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[23]
Myocardial ischemia	DISFTVXF	Strong	Genetic Variation	[24]
Myopathy due to myoadenylate deaminase deficiency	DISBLX65	Strong	Autosomal recessive	[25]
Neoplasm	DISZKGEW	Strong	Altered Expression	[22]
Obesity	DIS47Y1K	Strong	Genetic Variation	[14]
Prostate cancer	DISF190Y	Strong	Biomarker	[26]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[27]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[12]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[4]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[28]
Glycogen storage disease V	DISJNC0O	moderate	Biomarker	[29]
Hutchinson-Gilford progeria syndrome	DISY55BU	moderate	Biomarker	[30]
Myopathy	DISOWG27	moderate	Biomarker	[31]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[11]
Adenosine monophosphate deaminase deficiency	DISY0LK9	Supportive	Autosomal recessive	[32]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[33]
Barrett esophagus	DIS416Y7	Limited	Altered Expression	[33]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[34]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[34]
Cardiac failure	DISDC067	Limited	Genetic Variation	[35]
Congestive heart failure	DIS32MEA	Limited	Genetic Variation	[35]
Esophageal adenocarcinoma	DISODWFP	Limited	Altered Expression	[33]
Esophageal cancer	DISGB2VN	Limited	Biomarker	[33]
Hyperglycemia	DIS0BZB5	Limited	Genetic Variation	[13]
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⏷ Show the Full List of 50 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	AMP deaminase 1 (AMPD1) affects the response to substance of Methotrexate.	[27]
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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 affects the methylation of AMP deaminase 1 (AMPD1).	[36]
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1 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 AMP deaminase 1 (AMPD1).	[37]
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References

1	MMP-9 silencing regulates hTERT expression via 1 integrin-mediated FAK signaling and induces senescence in glioma xenograft cells.Cell Signal. 2011 Dec;23(12):2065-75. doi: 10.1016/j.cellsig.2011.08.001. Epub 2011 Aug 9.
2	Molecular analysis of Spanish patients with AMP deaminase deficiency.Muscle Nerve. 2000 Aug;23(8):1175-8. doi: 10.1002/1097-4598(200008)23:8<1175::aid-mus3>3.0.co;2-m.
3	Evaluation of AMPD1 C34T genotype as a predictor of mortality in heart failure and post-myocardial infarction patients.Am Heart J. 2006 Aug;152(2):312-20. doi: 10.1016/j.ahj.2005.12.015.
4	SELF BLOOD GLUCOSE MONITORING UNDERESTIMATES HYPERGLYCEMIA AND HYPOGLYCEMIA AS COMPARED TO CONTINUOUS GLUCOSE MONITORING IN TYPE 1 AND TYPE 2 DIABETES.Endocr Pract. 2018 Jan;24(1):47-52. doi: 10.4158/EP-2017-0032. Epub 2017 Nov 16.
5	Expression of serum AMPD1 in thyroid carcinoma and its clinical significance.Exp Ther Med. 2018 Apr;15(4):3357-3361. doi: 10.3892/etm.2018.5859. Epub 2018 Feb 12.
6	Too MAD or not MAD enough: The duplicitous role of the spindle assembly checkpoint protein MAD2 in cancer.Cancer Lett. 2020 Jan 28;469:11-21. doi: 10.1016/j.canlet.2019.10.005. Epub 2019 Oct 5.
7	Effects of the MYC oncogene antagonist, MAD, on proliferation, cell cycling and the malignant phenotype of human brain tumour cells.Nat Med. 1995 Jul;1(7):638-43. doi: 10.1038/nm0795-638.
8	Common and specific genes and peripheral biomarkers in children and adults with attention-deficit/hyperactivity disorder.World J Biol Psychiatry. 2018 Mar;19(2):80-100. doi: 10.1080/15622975.2017.1282175. Epub 2017 Feb 24.
9	AMPD1 functional variants associated with autism in Han Chinese population.Eur Arch Psychiatry Clin Neurosci. 2015 Sep;265(6):511-7. doi: 10.1007/s00406-014-0524-6. Epub 2014 Aug 26.
10	Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study.Lancet Oncol. 2017 Aug;18(8):1076-1088. doi: 10.1016/S1470-2045(17)30444-8. Epub 2017 Jun 28.
11	Overexpression of the mitotic checkpoint genes BUB1 and BUBR1 is associated with genomic complexity in clear cell kidney carcinomas.Cell Oncol. 2008;30(5):389-95. doi: 10.3233/clo-2008-0439.
12	Assignment of the human MAD and MXI1 genes to chromosomes 2p12-p13 and 10q24-q25.Genomics. 1994 Sep 1;23(1):282-5. doi: 10.1006/geno.1994.1496.
13	Association of C34T AMPD1 gene polymorphism with features of metabolic syndrome in patients with coronary artery disease or heart failure.Scand J Clin Lab Invest. 2009;69(1):102-12. doi: 10.1080/00365510802430964.
14	AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases.J Appl Genet. 2011 Feb;52(1):67-76. doi: 10.1007/s13353-010-0009-x. Epub 2010 Nov 25.
15	Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients.Antimicrob Agents Chemother. 2016 Oct 21;60(11):6726-6734. doi: 10.1128/AAC.00724-16. Print 2016 Nov.
16	Cytomegalovirus infection stimulates expression of monocyte-associated mediator genes.J Immunol. 1989 Nov 15;143(10):3343-52.
17	Unravelling the Prospective Associations Between Mixed Anxiety-Depression and Insomnia During the Course of Cognitive Behavioral Therapy.Psychosom Med. 2019 May;81(4):333-340. doi: 10.1097/PSY.0000000000000676.
18	Role of adenosine monophosphate deaminase-1 gene polymorphism in patients with congestive heart failure (influence on tumor necrosis factor-alpha level and outcome).Am J Cardiol. 2004 May 15;93(10):1260-4. doi: 10.1016/j.amjcard.2004.02.011.
19	Association between the C34T polymorphism of the AMPD1 gene and essential hypertension in Malaysian patients.Genet Mol Res. 2016 Jun 20;15(2). doi: 10.4238/gmr.15026241.
20	Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver.PLoS One. 2012;7(11):e48801. doi: 10.1371/journal.pone.0048801. Epub 2012 Nov 9.
21	Single- and multiple-ascending-dose studies of the NS3 protease inhibitor asunaprevir in subjects with or without chronic hepatitis C.Antimicrob Agents Chemother. 2012 Apr;56(4):1838-44. doi: 10.1128/AAC.05854-11. Epub 2012 Jan 30.
22	Expression patterns of AMP-deaminase isozymes in human hepatocellular carcinoma (HCC).Mol Cell Biochem. 2008 Nov;318(1-2):1-5. doi: 10.1007/s11010-008-9773-x. Epub 2008 May 21.
23	Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers.Cancer Lett. 2001 Jan 26;162(2):201-5. doi: 10.1016/s0304-3835(00)00675-3.
24	AMP deaminase 1 gene polymorphism and heart disease-a genetic association that highlights new treatment.Cardiovasc Drugs Ther. 2014 Apr;28(2):183-9. doi: 10.1007/s10557-013-6506-5.
25	Myoadenylate deaminase deficiency. A common inherited defect with heterogeneous clinical presentation. Neurol Clin. 2000 Feb;18(1):185-94. doi: 10.1016/s0733-8619(05)70184-5.
26	Antigen-specific IgG elicited in subjects with prostate cancer treated with flt3 ligand.J Immunother. 2005 May-Jun;28(3):268-75. doi: 10.1097/01.cji.0000158853.15664.0c.
27	Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2006 Sep;54(9):2830-9. doi: 10.1002/art.22032.
28	Effects of AMPD1 gene C34T polymorphism on cardiac index, blood pressure and prognosis in patients with cardiovascular diseases: a meta-analysis.BMC Cardiovasc Disord. 2017 Jul 3;17(1):174. doi: 10.1186/s12872-017-0608-0.
29	Exercise testing-based algorithms to diagnose McArdle disease and MAD defects.Acta Neurol Scand. 2018 Oct;138(4):301-307. doi: 10.1111/ane.12957. Epub 2018 May 10.
30	ZMPSTE24 missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or protein stability.Dis Model Mech. 2018 Jul 13;11(7):dmm033670. doi: 10.1242/dmm.033670.
31	Metabolic myopathies discovered during investigations of statin myopathy.Can J Neurol Sci. 2008 Mar;35(1):94-7. doi: 10.1017/s0317167100007630.
32	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.
33	Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network.Br J Cancer. 2008 Jun 17;98(12):1985-92. doi: 10.1038/sj.bjc.6604398. Epub 2008 May 20.
34	Inhibitory role of large intergenic noncoding RNA-ROR on tamoxifen resistance in the endocrine therapy of breast cancer by regulating the PI3K/Akt/mTOR signaling pathway.J Cell Physiol. 2019 Feb;234(2):1904-1912. doi: 10.1002/jcp.27066. Epub 2018 Aug 26.
35	Effects of AMPD1 common mutation on the metabolic-chronotropic relationship: Insights from patients with myoadenylate deaminase deficiency.PLoS One. 2017 Nov 2;12(11):e0187266. doi: 10.1371/journal.pone.0187266. eCollection 2017.
36	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.
37	BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
38	Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2006 Sep;54(9):2830-9. doi: 10.1002/art.22032.