Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGCV24S)

DOT Name Adenosine deaminase 2 (ADA2)
Synonyms EC 3.5.4.4; Cat eye syndrome critical region protein 1
Gene Name ADA2
Related Disease
Anxiety ( )
Anxiety disorder ( )
Deficiency of adenosine deaminase 2 ( )
Glioma ( )
Lung cancer ( )
Lung carcinoma ( )
Autism ( )
Behcet disease ( )
Childhood acute lymphoblastic leukemia ( )
Colon cancer ( )
Colon carcinoma ( )
Diabetic retinopathy ( )
Diamond-Blackfan anemia 1 ( )
Diamond-Blackfan anemia 6 ( )
Familial Mediterranean fever ( )
Focal segmental glomerulosclerosis ( )
Kaposi sarcoma ( )
Leukemia ( )
Malaria ( )
Malignant glioma ( )
Myeloid leukaemia ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Obesity ( )
Osteoarthritis ( )
Polycystic ovarian syndrome ( )
Rheumatoid arthritis ( )
Skin cancer ( )
Stroke ( )
Uveal Melanoma ( )
Vascular disease ( )
Vasculitis ( )
Vasculitis due to ADA2 deficiency ( )
Advanced cancer ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Polyarteritis nodosa ( )
Sneddon syndrome ( )
Diamond-Blackfan anemia ( )
Adult lymphoma ( )
Asthma ( )
Inflammation ( )
Leukopenia ( )
Lymphoma ( )
Pancreatic cancer ( )
Pediatric lymphoma ( )
Plasma cell myeloma ( )
Type-1 diabetes ( )
UniProt ID
ADA2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3LGD; 3LGG
EC Number
3.5.4.4
Pfam ID
PF00962 ; PF08451
Sequence
MLVDGPSERPALCFLLLAVAMSFFGSALSIDETRAHLLLKEKMMRLGGRLVLNTKEELAN
ERLMTLKIAEMKEAMRTLIFPPSMHFFQAKHLIERSQVFNILRMMPKGAALHLHDIGIVT
MDWLVRNVTYRPHCHICFTPRGIMQFRFAHPTPRPSEKCSKWILLEDYRKRVQNVTEFDD
SLLRNFTLVTQHPEVIYTNQNVVWSKFETIFFTISGLIHYAPVFRDYVFRSMQEFYEDNV
LYMEIRARLLPVYELSGEHHDEEWSVKTYQEVAQKFVETHPEFIGIKIIYSDHRSKDVAV
IAESIRMAMGLRIKFPTVVAGFDLVGHEDTGHSLHDYKEALMIPAKDGVKLPYFFHAGET
DWQGTSIDRNILDALMLNTTRIGHGFALSKHPAVRTYSWKKDIPIEVCPISNQVLKLVSD
LRNHPVATLMATGHPMVISSDDPAMFGAKGLSYDFYEVFMGIGGMKADLRTLKQLAMNSI
KYSTLLESEKNTFMEIWKKRWDKFIADVATK
Function
Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses. Requires elevated adenosine levels for optimal enzyme activity. Binds to cell surfaces via proteoglycans and may play a role in the regulation of cell proliferation and differentiation, independently of its enzyme activity.
Tissue Specificity
Detected in blood plasma (at protein level). Widely expressed, with most abundant expression in human adult heart, lung, lymphoblasts, and placenta as well as fetal lung, liver, and kidney. In embryo, expressed in the outflow tract and atrium of the developing heart, the VII/VIII cranial nerve ganglion, and the notochord.
KEGG Pathway
Purine metabolism (hsa00230 )
Metabolic pathways (hsa01100 )
Nucleotide metabolism (hsa01232 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Surfactant metabolism (R-HSA-5683826 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Anxiety DISIJDBA Definitive Genetic Variation [1]
Anxiety disorder DISBI2BT Definitive Genetic Variation [1]
Deficiency of adenosine deaminase 2 DISRVYPK Definitive Autosomal recessive [2]
Glioma DIS5RPEH Definitive Biomarker [3]
Lung cancer DISCM4YA Definitive Genetic Variation [1]
Lung carcinoma DISTR26C Definitive Genetic Variation [1]
Autism DISV4V1Z Strong Biomarker [4]
Behcet disease DISSYMBS Strong Altered Expression [5]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [6]
Colon cancer DISVC52G Strong Biomarker [7]
Colon carcinoma DISJYKUO Strong Biomarker [7]
Diabetic retinopathy DISHGUJM Strong Biomarker [8]
Diamond-Blackfan anemia 1 DISP4NUV Strong Biomarker [9]
Diamond-Blackfan anemia 6 DIS4FKKF Strong GermlineCausalMutation [9]
Familial Mediterranean fever DISVP5WP Strong Biomarker [10]
Focal segmental glomerulosclerosis DISJNHH0 Strong Biomarker [11]
Kaposi sarcoma DISC1H1Z Strong Biomarker [12]
Leukemia DISNAKFL Strong Genetic Variation [13]
Malaria DISQ9Y50 Strong Genetic Variation [14]
Malignant glioma DISFXKOV Strong Biomarker [15]
Myeloid leukaemia DISMN944 Strong Biomarker [16]
Neoplasm DISZKGEW Strong Biomarker [17]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [18]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [19]
Obesity DIS47Y1K Strong Genetic Variation [18]
Osteoarthritis DIS05URM Strong Biomarker [20]
Polycystic ovarian syndrome DISZ2BNG Strong Genetic Variation [21]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [22]
Skin cancer DISTM18U Strong Biomarker [17]
Stroke DISX6UHX Strong Genetic Variation [23]
Uveal Melanoma DISA7ZGL Strong Biomarker [24]
Vascular disease DISVS67S Strong Altered Expression [25]
Vasculitis DISQRKDX Strong Biomarker [26]
Vasculitis due to ADA2 deficiency DIS1UHPY Strong Autosomal recessive [27]
Advanced cancer DISAT1Z9 moderate Genetic Variation [13]
Coronary atherosclerosis DISKNDYU moderate Genetic Variation [28]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [28]
Polyarteritis nodosa DISRQ5X8 Moderate Autosomal recessive [27]
Sneddon syndrome DIS5FJHE Moderate Autosomal recessive [27]
Diamond-Blackfan anemia DISI2SNW Supportive Autosomal dominant [9]
Adult lymphoma DISK8IZR Limited Biomarker [29]
Asthma DISW9QNS Limited Biomarker [30]
Inflammation DISJUQ5T Limited Biomarker [31]
Leukopenia DISJMBMM Limited Genetic Variation [32]
Lymphoma DISN6V4S Limited Biomarker [29]
Pancreatic cancer DISJC981 Limited Biomarker [33]
Pediatric lymphoma DIS51BK2 Limited Biomarker [29]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [34]
Type-1 diabetes DIS7HLUB Limited Genetic Variation [35]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Adenosine deaminase 2 (ADA2). [36]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Adenosine deaminase 2 (ADA2). [37]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Adenosine deaminase 2 (ADA2). [38]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Adenosine deaminase 2 (ADA2). [40]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Adenosine deaminase 2 (ADA2). [41]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Adenosine deaminase 2 (ADA2). [42]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Adenosine deaminase 2 (ADA2). [40]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Adenosine deaminase 2 (ADA2). [43]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Adenosine deaminase 2 (ADA2). [45]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Adenosine deaminase 2 (ADA2). [46]
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⏷ Show the Full List of 10 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Adenosine deaminase 2 (ADA2). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Adenosine deaminase 2 (ADA2). [44]
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References

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2 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.
3 Comparative proteomic analysis of cat eye syndrome critical region protein 1- function in tumor-associated macrophages and immune response regulation of glial tumors.Oncotarget. 2018 Sep 11;9(71):33500-33514. doi: 10.18632/oncotarget.26063. eCollection 2018 Sep 11.
4 Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies.Am J Med Genet. 2000 Dec 4;96(6):784-90.
5 Genetics of vasculitis.Curr Opin Rheumatol. 2015 Jan;27(1):10-7. doi: 10.1097/BOR.0000000000000124.
6 Recent advances in childhood vasculitis.Curr Opin Rheumatol. 2017 Sep;29(5):530-534. doi: 10.1097/BOR.0000000000000424.
7 A study of three polymorphic sites of ADA gene in colon cancer.Cancer Invest. 2010 Dec;28(10):989-92. doi: 10.3109/07357907.2010.483501. Epub 2010 Jun 30.
8 Adenosine Deaminase-2-Induced Hyperpermeability in Human Retinal Vascular Endothelial Cells Is Suppressed by MicroRNA-146b-3p.Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):933-943. doi: 10.1167/iovs.16-19782.
9 The Genetic Landscape of Diamond-Blackfan Anemia. Am J Hum Genet. 2018 Dec 6;103(6):930-947. doi: 10.1016/j.ajhg.2018.10.027. Epub 2018 Nov 29.
10 Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study.Rheumatol Int. 2019 May;39(5):911-919. doi: 10.1007/s00296-019-04252-5. Epub 2019 Feb 19.
11 Recent advances of animal model of focal segmental glomerulosclerosis.Clin Exp Nephrol. 2018 Aug;22(4):752-763. doi: 10.1007/s10157-018-1552-8. Epub 2018 Mar 20.
12 Two herpesviral noncoding PAN RNAs are functionally homologous but do not associate with common chromatin loci.PLoS Pathog. 2018 Nov 1;14(11):e1007389. doi: 10.1371/journal.ppat.1007389. eCollection 2018 Nov.
13 Single-Molecule Sequencing Reveals Patterns of Preexisting Drug Resistance That Suggest Treatment Strategies in Philadelphia-Positive Leukemias.Clin Cancer Res. 2018 Nov 1;24(21):5321-5334. doi: 10.1158/1078-0432.CCR-18-0167. Epub 2018 Jul 24.
14 Adaptation to past malarial endemia and susceptibility to common diseases in modern populations: a study of adenosine deaminase and MN blood group genetic polymorphisms.Am J Phys Anthropol. 2005 Sep;128(1):194-8. doi: 10.1002/ajpa.20019.
15 CECR1-mediated cross talk between macrophages and vascular mural cells promotes neovascularization in malignant glioma.Oncogene. 2017 Sep 21;36(38):5356-5368. doi: 10.1038/onc.2017.145. Epub 2017 May 22.
16 Systematic identification of genes involved in metabolic acid stress resistance in yeast and their potential as cancer targets.Dis Model Mech. 2016 Sep 1;9(9):1039-49. doi: 10.1242/dmm.023374. Epub 2016 Aug 12.
17 Design, Synthesis, and Biological Evaluation of Polyaminocarboxylate Ligand-Based Theranostic Conjugates for Antibody-Targeted Cancer Therapy and Near-Infrared Optical Imaging.ChemMedChem. 2018 Dec 20;13(24):2606-2617. doi: 10.1002/cmdc.201800598. Epub 2018 Nov 26.
18 Adenosine deaminase and body mass index in non-insulin-dependent diabetes mellitus.Metabolism. 1999 Aug;48(8):949-51. doi: 10.1016/s0026-0495(99)90187-7.
19 The Proto-oncogene PKC regulates the alternative splicing of Bcl-x pre-mRNA.Mol Cancer Res. 2012 May;10(5):660-9. doi: 10.1158/1541-7786.MCR-11-0363. Epub 2012 Apr 20.
20 Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts.Arthritis Rheum. 2003 Mar;48(3):668-74. doi: 10.1002/art.10956.
21 Association of G22A and A4223C ADA1 gene polymorphisms and ADA activity with PCOS.Syst Biol Reprod Med. 2016 Jun;62(3):213-22. doi: 10.3109/19396368.2016.1143055. Epub 2016 Mar 15.
22 A study of Adenosine-Deaminase genetic polymorphism in rheumatoid arthritis.Int J Immunopathol Pharmacol. 2010 Jul-Sep;23(3):791-5. doi: 10.1177/039463201002300313.
23 Identification of Novel Adenosine Deaminase 2 Gene Variants and Varied Clinical Phenotype in Pediatric Vasculitis.Arthritis Rheumatol. 2019 Oct;71(10):1747-1755. doi: 10.1002/art.40913. Epub 2019 Aug 26.
24 Nanobodies against surface biomarkers enable the analysis of tumor genetic heterogeneity in uveal melanoma patient-derived xenografts.Pigment Cell Melanoma Res. 2017 May;30(3):317-327. doi: 10.1111/pcmr.12577. Epub 2017 Apr 19.
25 What's new in autoinflammation?.Pediatr Nephrol. 2019 Dec;34(12):2449-2456. doi: 10.1007/s00467-018-4155-4. Epub 2018 Dec 14.
26 A monogenic autoinflammatory disease with fatal vasculitis: deficiency of adenosine deaminase 2.Curr Opin Rheumatol. 2020 Jan;32(1):3-14. doi: 10.1097/BOR.0000000000000669.
27 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
28 ADA*2 allele of the adenosine deaminase gene may protect against coronary artery disease.Cardiology. 2007;108(4):275-81. doi: 10.1159/000099096. Epub 2007 Feb 8.
29 A rare case of asynchronous bilateral B-cell lymphoma of the breast.Jpn J Clin Oncol. 1989 Dec;19(4):391-6.
30 ADA polymorphisms and asthma: a study in the Chinese Han population.J Asthma. 2006 Apr;43(3):203-6. doi: 10.1080/02770900600566827.
31 ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation.Front Immunol. 2019 Jan 14;9:2767. doi: 10.3389/fimmu.2018.02767. eCollection 2018.
32 Novel Mutation in CECR1 Leads to Deficiency of ADA2 with Associated Neutropenia.J Clin Immunol. 2018 Apr;38(3):273-277. doi: 10.1007/s10875-018-0487-x. Epub 2018 Mar 21.
33 Procedures and recommended times in the care process of the patient with pancreatic cancer: PAN-TIME consensus between scientific societies.Clin Transl Oncol. 2017 Jul;19(7):834-843. doi: 10.1007/s12094-016-1609-7. Epub 2017 Jan 19.
34 Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data.Appl Health Econ Health Policy. 2017 Feb;15(1):45-55. doi: 10.1007/s40258-016-0271-0.
35 A study of three polymorphic sites of the ADA gene in children with type 1 diabetes mellitus.J Pediatr Endocrinol Metab. 2010 Mar;23(3):283-90. doi: 10.1515/jpem.2010.23.3.283.
36 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
37 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
38 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
39 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
40 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
41 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
42 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
43 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
44 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
45 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
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