Details of Drug Off-Target (DOT)

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

DOT Name	Podocin (NPHS2)
Gene Name	NPHS2
Related Disease	Chronic renal failure ( ) Nephrotic syndrome, type 2 ( ) Amyloidosis ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Autosomal dominant polycystic kidney disease ( ) Azoospermia ( ) Childhood kidney Wilms tumor ( ) Chronic kidney disease ( ) Congenital nephrotic syndrome, Finnish type ( ) Eclampsia ( ) End-stage renal disease ( ) Glomerulonephritis ( ) Glomerulosclerosis ( ) Idiopathic nephrotic syndrome ( ) IgA nephropathy ( ) Membranous glomerulonephritis ( ) Metabolic disorder ( ) Myocardial ischemia ( ) Nephritis ( ) Nephropathy ( ) Purpura ( ) Trichohepatoenteric syndrome ( ) Type-1/2 diabetes ( ) Wilms tumor ( ) Autosomal dominant medullary cystic kidney disease with or without hyperuricemia ( ) Familial nephrotic syndrome ( ) Macular corneal dystrophy ( ) Nephrotic syndrome ( ) Pierson syndrome ( ) Renal fibrosis ( ) Familial idiopathic steroid-resistant nephrotic syndrome ( ) Kidney failure ( ) Diphtheria ( ) Fabry disease ( ) Hematuria, benign familial ( ) High blood pressure ( )
UniProt ID	PODO_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01145
Sequence	MERRARSSSRESRGRGGRTPHKENKRAKAERSGGGRGRQEAGPEPSGSGRAGTPGEPRAP AATVVDVDEVRGSGEEGTEVVALLESERPEEGTKSSGLGACEWLLVLISLLFIIMTFPFS IWFCVKVVQEYERVIIFRLGHLLPGRAKGPGLFFFLPCLDTYHKVDLRLQTLEIPFHEIV TKDMFIMEIDAICYYRMENASLLLSSLAHVSKAVQFLVQTTMKRLLAHRSLTEILLERKS IAQDAKVALDSVTCIWGIKVERIEIKDVRLPAGLQHSLAVEAEAQRQAKVRMIAAEAEKA ASESLRMAAEILSGTPAAVQLRYLHTLQSLSTEKPSTVVLPLPFDLLNCLSSPSNRTQGS LPFPSPSKPVEPLNPKKKDSPML
Function	Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton.
Tissue Specificity	Almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli.
Reactome Pathway	Nephrin family interactions (R-HSA-373753 )

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Nephrotic syndrome, type 2	DISIRFO1	Definitive	Autosomal recessive	[2]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[4]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[4]
Autosomal dominant polycystic kidney disease	DISBHWUI	Strong	Altered Expression	[5]
Azoospermia	DIS94181	Strong	Altered Expression	[6]
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Altered Expression	[7]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[8]
Congenital nephrotic syndrome, Finnish type	DIS8P7EH	Strong	Genetic Variation	[9]
Eclampsia	DISWPO8U	Strong	Altered Expression	[10]
End-stage renal disease	DISXA7GG	Strong	Genetic Variation	[1]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[11]
Glomerulosclerosis	DISJF20Z	Strong	Biomarker	[12]
Idiopathic nephrotic syndrome	DISV4XYG	Strong	CausalMutation	[13]
IgA nephropathy	DISZ8MTK	Strong	Altered Expression	[14]
Membranous glomerulonephritis	DISFSUKQ	Strong	Biomarker	[15]
Metabolic disorder	DIS71G5H	Strong	Altered Expression	[16]
Myocardial ischemia	DISFTVXF	Strong	Genetic Variation	[4]
Nephritis	DISQZQ70	Strong	Biomarker	[17]
Nephropathy	DISXWP4P	Strong	Biomarker	[18]
Purpura	DISWPOOE	Strong	Biomarker	[17]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[19]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[20]
Wilms tumor	DISB6T16	Strong	Genetic Variation	[21]
Autosomal dominant medullary cystic kidney disease with or without hyperuricemia	DIS3PLLZ	moderate	Genetic Variation	[22]
Familial nephrotic syndrome	DISADF8G	moderate	Genetic Variation	[21]
Macular corneal dystrophy	DISOLD0H	moderate	Biomarker	[23]
Nephrotic syndrome	DISSPSC2	moderate	Genetic Variation	[24]
Pierson syndrome	DIS0DF3C	moderate	Biomarker	[25]
Renal fibrosis	DISMHI3I	moderate	Biomarker	[12]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[26]
Kidney failure	DISOVQ9P	Disputed	Genetic Variation	[27]
Diphtheria	DISZWM55	Limited	Biomarker	[28]
Fabry disease	DISUUQJF	Limited	Altered Expression	[29]
Hematuria, benign familial	DISCWU1L	Limited	Biomarker	[30]
High blood pressure	DISY2OHH	Limited	Altered Expression	[31]
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⏷ Show the Full List of 37 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

4 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 Podocin (NPHS2).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Podocin (NPHS2).	[33]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Podocin (NPHS2).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Podocin (NPHS2).	[36]
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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 Podocin (NPHS2).	[35]
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References

1	An inducible mouse model of podocin-mutation-related nephrotic syndrome.PLoS One. 2017 Oct 19;12(10):e0186574. doi: 10.1371/journal.pone.0186574. eCollection 2017.
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	Hsf-1 affects podocyte markers NPHS1, NPHS2 and WT1 in a transgenic mouse model of TTRVal30Met-related amyloidosis.Amyloid. 2013 Sep;20(3):164-72. doi: 10.3109/13506129.2013.814046. Epub 2013 Jul 5.
4	Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease.Circulation. 2002 Mar 26;105(12):1440-5. doi: 10.1161/01.cir.0000012145.80593.25.
5	Podocyte Injury in Autosomal Dominant Polycystic Kidney Disease.Nephron. 2019;142(4):311-319. doi: 10.1159/000499741. Epub 2019 May 22.
6	New perspectives on the renal slit diaphragm protein podocin.Mod Pathol. 2011 Aug;24(8):1101-10. doi: 10.1038/modpathol.2011.58. Epub 2011 Apr 15.
7	Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptor 2 Agonist.J Pharmacol Exp Ther. 2018 Oct;367(1):82-94. doi: 10.1124/jpet.118.249375. Epub 2018 Jul 27.
8	Stabilization of hypoxia-inducible factor 1 by cobalt chloride impairs podocyte morphology and slit-diaphragm function.J Cell Biochem. 2019 May;120(5):7667-7678. doi: 10.1002/jcb.28041. Epub 2018 Nov 1.
9	Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration. Hum Mol Genet. 2002 Feb 15;11(4):379-88. doi: 10.1093/hmg/11.4.379.
10	The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an L-NAME model of pre-eclampsia.Mol Cell Biochem. 2017 Mar;427(1-2):59-67. doi: 10.1007/s11010-016-2897-5. Epub 2016 Dec 19.
11	Evaluation of Tryptic Podocin Peptide in Urine Sediment Using LC-MS-MRM Method as a Potential Biomarker of Glomerular Injury in Dogs with Clinical Signs of Renal and Cardiac Disorders.Molecules. 2019 Aug 26;24(17):3088. doi: 10.3390/molecules24173088.
12	Salidroside ameliorates Adriamycin nephropathy in mice by inhibiting -catenin activity.J Cell Mol Med. 2019 Jun;23(6):4443-4453. doi: 10.1111/jcmm.14340. Epub 2019 Apr 16.
13	Endoplasmic reticulum-retained podocin mutants are massively degraded by the proteasome.J Biol Chem. 2018 Mar 16;293(11):4122-4133. doi: 10.1074/jbc.RA117.001159. Epub 2018 Jan 30.
14	Sorting Nexin 9 facilitates podocin endocytosis in the injured podocyte.Sci Rep. 2017 Mar 7;7:43921. doi: 10.1038/srep43921.
15	The transcriptional regulation of podocin (NPHS2) by Lmx1b and a promoter single nucleotide polymorphism.Cell Mol Biol Lett. 2009;14(4):679-91. doi: 10.2478/s11658-009-0026-0. Epub 2009 Jun 27.
16	Wenshen Jianpi recipe, a blended traditional Chinese medicine, ameliorates proteinuria and renal injury in a rat model of diabetic nephropathy.BMC Complement Altern Med. 2019 Jul 30;19(1):193. doi: 10.1186/s12906-019-2598-1.
17	Lack of association between NPHS2 gene polymorphisms and Henoch-Schnlein purpura nephritis.Arch Dermatol Res. 2007 Jun;299(3):151-5. doi: 10.1007/s00403-007-0752-y. Epub 2007 Mar 29.
18	Epidermal growth factor receptor and podocin predict nephropathy progression in type 2 diabetic patients through interaction with the autophagy influencer ULK-1.J Diabetes Complications. 2019 Feb;33(2):128-133. doi: 10.1016/j.jdiacomp.2018.11.007. Epub 2018 Nov 22.
19	Mutations in NPHS2 in sporadic steroid-resistant nephrotic syndrome in Chinese children.Nephrol Dial Transplant. 2005 May;20(5):902-8. doi: 10.1093/ndt/gfh769. Epub 2005 Mar 15.
20	Euterpe oleracea Mart. seed extract protects against renal injury in diabetic and spontaneously hypertensive rats: role of inflammation and oxidative stress.Eur J Nutr. 2018 Mar;57(2):817-832. doi: 10.1007/s00394-016-1371-1. Epub 2017 Jan 20.
21	Cyclosporine A responsive congenital nephrotic syndrome with single heterozygous variants in NPHS1, NPHS2, and PLCE1.Pediatr Nephrol. 2018 Jul;33(7):1269-1272. doi: 10.1007/s00467-018-3961-z. Epub 2018 Apr 16.
22	Endoplasmic reticulum stress and monogenic kidney diseases in precision nephrology.Pediatr Nephrol. 2019 Sep;34(9):1493-1500. doi: 10.1007/s00467-018-4031-2. Epub 2018 Aug 11.
23	Podocin and uPAR are good biomarkers in cases of Focal and segmental glomerulosclerosis in pediatric renal biopsies.PLoS One. 2019 Jun 12;14(6):e0217569. doi: 10.1371/journal.pone.0217569. eCollection 2019.
24	Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications for Genetic Counseling.Am J Kidney Dis. 2019 Mar;73(3):400-403. doi: 10.1053/j.ajkd.2018.06.034. Epub 2018 Sep 18.
25	Molecular pathology of nephrotic syndrome in childhood: a contemporary approach to diagnosis.Pediatr Dev Pathol. 2008 Jul-Aug;11(4):154-63. doi: 10.2350/07-11-0375.1.
26	Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2002 Feb;13(2):388-393. doi: 10.1681/ASN.V132388.
27	Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis.Int J Mol Sci. 2019 Jan 26;20(3):519. doi: 10.3390/ijms20030519.
28	Urine podocyte mRNAs mark progression of renal disease.J Am Soc Nephrol. 2009 May;20(5):1041-52. doi: 10.1681/ASN.2007121328. Epub 2009 Apr 23.
29	Tandem mass spectrometry analysis of urinary podocalyxin and podocin in the investigation of podocyturia in women with preeclampsia and Fabry disease patients.Clin Chim Acta. 2019 Aug;495:67-75. doi: 10.1016/j.cca.2019.03.1615. Epub 2019 Mar 19.
30	Co-Inheritance of Functional Podocin Variants with Heterozygous Collagen IV Mutations Predisposes to Renal Failure.Nephron. 2015;130(3):200-12. doi: 10.1159/000432406. Epub 2015 Jun 26.
31	Effects of the novel nonsteroidal mineralocorticoid receptor blocker, esaxerenone (CS-3150), on blood pressure and urinary angiotensinogen in low-renin Dahl salt-sensitive hypertensive rats.Hypertens Res. 2019 Jun;42(6):769-778. doi: 10.1038/s41440-018-0187-1. Epub 2018 Dec 26.
32	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
33	Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
34	Simvastatin maintains steady patterns of GFR and improves AER and expression of slit diaphragm proteins in type II diabetes. Kidney Int. 2006 Jul;70(1):177-86. doi: 10.1038/sj.ki.5001515. Epub 2006 May 17.
35	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.
36	Bisphenol A impaired cell adhesion by altering the expression of adhesion and cytoskeleton proteins on human podocytes. Sci Rep. 2020 Oct 6;10(1):16638. doi: 10.1038/s41598-020-73636-6.