Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS7UF36)

DOT Name	Cytosolic 5'-nucleotidase 1A (NT5C1A)
Synonyms	cN1A; EC 3.1.3.5; EC 3.1.3.89; EC 3.1.3.99; 5'-deoxynucleotidase; Cytosolic 5'-nucleotidase IA; cN-I; cN-IA
Gene Name	NT5C1A
Related Disease	Chronic kidney disease ( ) Chronic renal failure ( ) End-stage renal disease ( ) Matthew-Wood syndrome ( ) Pancreatic cancer ( ) Pancreatic ductal carcinoma ( ) Pancreatic tumour ( ) Renal fibrosis ( ) Clear cell renal carcinoma ( ) Cyclic hematopoiesis ( ) Cytomegalovirus infection ( ) Graft-versus-host disease ( ) Juvenile idiopathic arthritis ( ) Kidney failure ( ) Leukopenia ( ) Mixed connective tissue disease ( ) Myositis disease ( ) Neoplasm ( ) Nephropathy ( ) Renal cell carcinoma ( ) Renal tubular acidosis ( ) Sjogren syndrome ( ) Systemic sclerosis ( ) High blood pressure ( ) leukaemia ( ) Leukemia ( ) Heterotaxy, visceral, 2, autosomal ( ) Dermatomyositis ( ) Erectile dysfunction ( ) Hepatitis C virus infection ( ) Lupus nephritis ( ) Polymyositis ( ) Systemic lupus erythematosus ( ) Thyroid gland papillary carcinoma ( )
UniProt ID	5NT1A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.1.3.5; 3.1.3.89; 3.1.3.99
Pfam ID	PF06189
Sequence	MEPGQPREPQEPREPGPGAETAAAPVWEEAKIFYDNLAPKKKPKSPKPQNAVTIAVSSRA LFRMDEEQQIYTEQGVEEYVRYQLEHENEPFSPGPAFPFVKALEAVNRRLRELYPDSEDV FDIVLMTNNHAQVGVRLINSINHYDLFIERFCMTGGNSPICYLKAYHTNLYLSADAEKVR EAIDEGIAAATIFSPSRDVVVSQSQLRVAFDGDAVLFSDESERIVKAHGLDRFFEHEKAH ENKPLAQGPLKGFLEALGRLQKKFYSKGLRLECPIRTYLVTARSAASSGARALKTLRSWG LETDEALFLAGAPKGPLLEKIRPHIFFDDQMFHVAGAQEMGTVAAHVPYGVAQTPRRTAP AKQAPSAQ
Function	Catalyzes the hydrolysis of ribonucleotide and deoxyribonucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside. AMP is the major substrate but can also hydrolyze dCMP and IMP.
Tissue Specificity	Highly expressed in skeletal muscle. Detected at intermediate levels in heart, brain, kidney and pancreas.
KEGG Pathway	Purine metabolism (hsa00230 ) Pyrimidine metabolism (hsa00240 ) Nicoti.te and nicoti.mide metabolism (hsa00760 ) Metabolic pathways (hsa01100 ) Nucleotide metabolism (hsa01232 )
Reactome Pathway	Purine catabolism (R-HSA-74259 ) Pyrimidine catabolism (R-HSA-73621 )
BioCyc Pathway	MetaCyc:HS04074-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Chronic kidney disease	DISW82R7	Definitive	Biomarker	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[2]
End-stage renal disease	DISXA7GG	Definitive	Genetic Variation	[2]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[3]
Pancreatic cancer	DISJC981	Definitive	Altered Expression	[3]
Pancreatic ductal carcinoma	DIS26F9Q	Definitive	Altered Expression	[3]
Pancreatic tumour	DIS3U0LK	Definitive	Biomarker	[3]
Renal fibrosis	DISMHI3I	Definitive	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[5]
Cyclic hematopoiesis	DISQQOM4	Strong	Biomarker	[6]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[7]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[8]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[9]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[10]
Leukopenia	DISJMBMM	Strong	Biomarker	[11]
Mixed connective tissue disease	DISXX0H8	Strong	Genetic Variation	[12]
Myositis disease	DISCIXF0	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[5]
Renal tubular acidosis	DISE1NDR	Strong	Biomarker	[14]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[12]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	moderate	Biomarker	[15]
leukaemia	DISS7D1V	moderate	Genetic Variation	[16]
Leukemia	DISNAKFL	moderate	Genetic Variation	[16]
Heterotaxy, visceral, 2, autosomal	DISPJ9QY	Disputed	Genetic Variation	[17]
Dermatomyositis	DIS50C5O	Limited	Biomarker	[18]
Erectile dysfunction	DISD8MTH	Limited	Biomarker	[19]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[20]
Lupus nephritis	DISCVGPZ	Limited	Biomarker	[21]
Polymyositis	DIS5DHFP	Limited	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Limited	Biomarker	[18]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[22]
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⏷ Show the Full List of 34 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
Azathioprine	DMMZSXQ	Approved	Cytosolic 5'-nucleotidase 1A (NT5C1A) increases the Bone marrow toxicity ADR of Azathioprine.	[25]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytosolic 5'-nucleotidase 1A (NT5C1A).	[23]
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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 increases the methylation of Cytosolic 5'-nucleotidase 1A (NT5C1A).	[24]
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References

1	Genetic variance in ABCB1 and CYP3A5 does not contribute toward the development of chronic kidney disease after liver transplantation.Pharmacogenet Genomics. 2014 Sep;24(9):427-35. doi: 10.1097/FPC.0000000000000063.
2	Evolution of lung and kidney allograft function in patients receiving kidney after lung transplantation.Clin Transplant. 2018 Feb;32(2). doi: 10.1111/ctr.13169. Epub 2017 Dec 21.
3	Cytosolic 5'-nucleotidase 1A is overexpressed in pancreatic cancer and mediates gemcitabine resistance by reducing intracellular gemcitabine metabolites.EBioMedicine. 2019 Feb;40:394-405. doi: 10.1016/j.ebiom.2019.01.037. Epub 2019 Jan 30.
4	Nox2 is a mediator of chronic CsA nephrotoxicity.Am J Transplant. 2012 Aug;12(8):1997-2007. doi: 10.1111/j.1600-6143.2012.04081.x. Epub 2012 May 8.
5	Honokiol inhibits c-Met-HO-1 tumor-promoting pathway and its cross-talk with calcineurin inhibitor-mediated renal cancer growth.Sci Rep. 2017 Jul 19;7(1):5900. doi: 10.1038/s41598-017-05455-1.
6	Analysis of bilirubin UDP-glucuronosyltransferase gene mutations in an unusual Crigler-Najjar syndrome patient.Mol Med Rep. 2012 Sep;6(3):667-9. doi: 10.3892/mmr.2012.950. Epub 2012 Jun 15.
7	Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.Cochrane Database Syst Rev. 2019 Dec 16;12(12):CD004290. doi: 10.1002/14651858.CD004290.pub3.
8	PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL.Blood Adv. 2019 Feb 12;3(3):360-369. doi: 10.1182/bloodadvances.2018027748.
9	Anti-NT5C1A autoantibodies are associated with more severe disease in patients with juvenile myositis.Ann Rheum Dis. 2018 May;77(5):714-719. doi: 10.1136/annrheumdis-2017-212436. Epub 2018 Jan 23.
10	A randomized trial of everolimus-based quadruple therapy vs standard triple therapy early after lung transplantation.Am J Transplant. 2019 Jun;19(6):1759-1769. doi: 10.1111/ajt.15251. Epub 2019 Feb 5.
11	Mammalian Target of Rapamycin Inhibitors Combined With Calcineurin Inhibitors as Initial Immunosuppression in Renal Transplantation: A Meta-analysis.Transplantation. 2019 Oct;103(10):2031-2056. doi: 10.1097/TP.0000000000002769.
12	Prevalence of anti-NT5C1A antibodies in Japanese patients with autoimmune rheumatic diseases in comparison with other patient cohorts.Clin Chim Acta. 2017 Sep;472:1-4. doi: 10.1016/j.cca.2017.07.002. Epub 2017 Jul 4.
13	Etiological analysis of graft dysfunction following living kidney transplantation: a report of 366 biopsies.Ren Fail. 2018 Nov;40(1):219-225. doi: 10.1080/0886022X.2018.1455592.
14	Clinical analysis of hyperkalemic renal tubular acidosis caused by calcineurin inhibitors in solid organ transplant recipients.J Clin Pharm Ther. 2017 Feb;42(1):122-124. doi: 10.1111/jcpt.12485. Epub 2016 Dec 14.
15	Pathophysiological mechanisms of calcineurin inhibitor-induced nephrotoxicity and arterial hypertension.Physiol Res. 2017 May 4;66(2):167-180. doi: 10.33549/physiolres.933332. Epub 2016 Dec 16.
16	Pharmacogenetic characterization of naturally occurring germline NT5C1A variants to chemotherapeutic nucleoside analogs.Pharmacogenet Genomics. 2016 Jun;26(6):271-9. doi: 10.1097/FPC.0000000000000208.
17	Effect of Calcineurin Inhibitor-Free, Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate After Heart Transplantation.Transplantation. 2017 Nov;101(11):2793-2800. doi: 10.1097/TP.0000000000001706.
18	Autoantibodies to Cytosolic 5'-Nucleotidase 1A in Primary Sjgren's Syndrome and Systemic Lupus Erythematosus.Front Immunol. 2018 Jun 5;9:1200. doi: 10.3389/fimmu.2018.01200. eCollection 2018.
19	M1 Macrophages Are Predominantly Recruited to the Major Pelvic Ganglion of the Rat Following Cavernous Nerve Injury.J Sex Med. 2017 Feb;14(2):187-195. doi: 10.1016/j.jsxm.2016.12.012.
20	Efficacy and safety of sofosbuvir-based antiviral therapy to treat hepatitis C virus infection after kidney transplantation.Clin Kidney J. 2018 Jun;11(3):429-433. doi: 10.1093/ckj/sfx112. Epub 2017 Oct 30.
21	Recurrence of disease following organ transplantation in autoimmune liver disease and systemic lupus erythematosus.Cell Immunol. 2020 Jan;347:104021. doi: 10.1016/j.cellimm.2019.104021. Epub 2019 Nov 16.
22	Computed Tomography-Detected Central Lymph Node Metastasis in Ultrasonography Node-Negative Papillary Thyroid Carcinoma: Is It Really Significant?.Ann Surg Oncol. 2017 Feb;24(2):442-449. doi: 10.1245/s10434-016-5552-1. Epub 2016 Sep 13.
23	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
24	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.
25	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.