Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWF4L0U)

• DOT Name: Transient receptor potential cation channel subfamily V member 5 (TRPV5)
• Synonyms: TrpV5; Calcium transport protein 2; CaT2; Epithelial calcium channel 1; ECaC; ECaC1; Osm-9-like TRP channel 3; OTRPC3
• Gene Name: TRPV5
• Related Disease:
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  B-cell neoplasm
  Cataract
  Chronic kidney disease
  Cystic fibrosis
  Familial hypocalciuric hypercalcemia 1
  High blood pressure
  Hypercalcaemia
  leukaemia
  Leukemia
  Neoplasm
  Non-small-cell lung cancer
  Osteoarthritis
  Pseudohypoaldosteronism type 2D
  Type-1/2 diabetes
  Urolithiasis
  Clear cell renal carcinoma
  Nephrocalcinosis
  Renal cell carcinoma
  Gitelman syndrome
  Pulmonary tuberculosis
• UniProt ID: TRPV5_HUMAN
• PDB ID: 5OEO
• Pfam ID: PF00023 ; PF12796 ; PF00520
• Sequence:
  MGGFLPKAEGPGSQLQKLLPSFLVREQDWDQHLDKLHMLQQKRILESPLLRASKENDLSV
  LRQLLLDCTCDVRQRGALGETALHIAALYDNLEAALVLMEAAPELVFEPTTCEAFAGQTA
  LHIAVVNQNVNLVRALLTRRASVSARATGTAFRHSPRNLIYFGEHPLSFAACVNSEEIVR
  LLIEHGADIRAQDSLGNTVLHILILQPNKTFACQMYNLLLSYDGHGDHLQPLDLVPNHQG
  LTPFKLAGVEGNTVMFQHLMQKRRHIQWTYGPLTSILYDLTEIDSWGEELSFLELVVSSD
  KREARQILEQTPVKELVSFKWNKYGRPYFCILAALYLLYMICFTTCCVYRPLKFRGGNRT
  HSRDITILQQKLLQEAYETREDIIRLVGELVSIVGAVIILLLEIPDIFRVGASRYFGKTI
  LGGPFHVIIITYASLVLVTMVMRLTNTNGEVVPMSFALVLGWCSVMYFTRGFQMLGPFTI
  MIQKMIFGDLMRFCWLMAVVILGFASAFYIIFQTEDPTSLGQFYDYPMALFTTFELFLTV
  IDAPANYDVDLPFMFSIVNFAFTIIATLLMLNLFIAMMGDTHWRVAQERDELWRAQVVAT
  TVMLERKLPRCLWPRSGICGCEFGLGDRWFLRVENHNDQNPLRVLRYVEVFKNSDKEDDQ
  EHPSEKQPSGAESGTLARASLALPTSSLSRTASQSSSHRGWEILRQNTLGHLNLGLNLSE
  GDGEEVYHF
• Function: Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine. Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules. The channel is activated by low internal calcium level and the current exhibits an inward rectification. A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay. Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating.
• Tissue Specificity: Expressed at high levels in kidney, small intestine and pancreas, and at lower levels in testis, prostate, placenta, brain, colon and rectum.
• KEGG Pathway:
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
• Reactome Pathway: TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[3]
Cataract	DISUD7SL	Strong	Genetic Variation	[4]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[5]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[6]
Familial hypocalciuric hypercalcemia 1	DISPW6O5	Strong	Biomarker	[7]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[7]
Hypercalcaemia	DISKQ2K7	Strong	Biomarker	[8]
leukaemia	DISS7D1V	Strong	Biomarker	[9]
Leukemia	DISNAKFL	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Osteoarthritis	DIS05URM	Strong	Biomarker	[12]
Pseudohypoaldosteronism type 2D	DIS2AO4N	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[13]
Urolithiasis	DISNFTKT	Strong	Genetic Variation	[14]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[15]
Nephrocalcinosis	DIS5ZVJP	moderate	Biomarker	[16]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[15]
Gitelman syndrome	DISEM9V2	Limited	Genetic Variation	[17]
Pulmonary tuberculosis	DIS6FLUM	Limited	Biomarker	[18]

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 Transient receptor potential cation channel subfamily V member 5 (TRPV5).	[19]

References

• [1] Cancer risk susceptibility loci in a Swedish population.Oncotarget. 2017 Nov 25;8(66):110300-110310. doi: 10.18632/oncotarget.22687. eCollection 2017 Dec 15.
• [2] Metabolic profiling of intra- and extracranial carotid artery atherosclerosis.Atherosclerosis. 2018 May;272:60-65. doi: 10.1016/j.atherosclerosis.2018.03.015. Epub 2018 Mar 8.
• [3] Transient Receptor Potential Vanilloid 5 Mediates Ca2+ Influx and Inhibits Chondrocyte Autophagy in a Rat Osteoarthritis Model.Cell Physiol Biochem. 2017;42(1):319-332. doi: 10.1159/000477387. Epub 2017 May 25.
• [4] Cataract mutations and lens development.Prog Retin Eye Res. 1999 Mar;18(2):235-67. doi: 10.1016/s1350-9462(98)00018-4.
• [5] Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase.PLoS One. 2017 Jan 20;12(1):e0170654. doi: 10.1371/journal.pone.0170654. eCollection 2017.
• [6] The low PLC-1 expression in cystic fibrosis bronchial epithelial cells induces upregulation of TRPV6 channel activity.Cell Calcium. 2015 Jan;57(1):38-48. doi: 10.1016/j.ceca.2014.11.005. Epub 2014 Nov 18.
• [7] WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4.Am J Physiol Renal Physiol. 2007 Feb;292(2):F545-54. doi: 10.1152/ajprenal.00187.2006. Epub 2006 Oct 3.
• [8] Structure-based characterization of novel TRPV5 inhibitors.Elife. 2019 Oct 25;8:e49572. doi: 10.7554/eLife.49572.
• [9] Endogenous expression of TRPV5 and TRPV6 calcium channels in human leukemia K562 cells.Am J Physiol Cell Physiol. 2009 May;296(5):C1098-104. doi: 10.1152/ajpcell.00435.2008. Epub 2009 Mar 18.
• [10] Expression and prognostic roles of TRPV5 and TRPV6 in non-small cell lung cancer after curative resection.Asian Pac J Cancer Prev. 2014;15(6):2559-63. doi: 10.7314/apjcp.2014.15.6.2559.
• [11] The construction and analysis of the aberrant lncRNA-miRNA-mRNA network in non-small cell lung cancer.J Thorac Dis. 2019 May;11(5):1772-1778. doi: 10.21037/jtd.2019.05.69.
• [12] Transient Receptor Potential Channel, Vanilloid 5, Induces Chondrocyte Apoptosis in a Rat Osteoarthritis Model Through the Mediation of Ca2+ Influx.Cell Physiol Biochem. 2018;46(2):687-698. doi: 10.1159/000488725. Epub 2018 Mar 29.
• [13] Relationship between catalase haplotype and arterial aging.Atherosclerosis. 2013 Mar;227(1):100-5. doi: 10.1016/j.atherosclerosis.2012.12.015. Epub 2013 Jan 8.
• [14] Association of TRPV5 gene polymorphism with calcium urolithiasis: a case-control study from West Bengal, India.World J Urol. 2020 May;38(5):1311-1322. doi: 10.1007/s00345-019-02911-7. Epub 2019 Aug 19.
• [15] Vitamin D receptor suppresses proliferation and metastasis in renal cell carcinoma cell lines via regulating the expression of the epithelial Ca2+ channel TRPV5.PLoS One. 2018 Apr 16;13(4):e0195844. doi: 10.1371/journal.pone.0195844. eCollection 2018.
• [16] Urinary plasmin inhibits TRPV5 in nephrotic-range proteinuria.J Am Soc Nephrol. 2012 Nov;23(11):1824-34. doi: 10.1681/ASN.2011111126. Epub 2012 Sep 27.
• [17] Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome.Hum Mutat. 2010 Dec;31(12):1304-15. doi: 10.1002/humu.21364. Epub 2010 Oct 14.
• [18] Efficacy and Safety of Mycobacterium indicus pranii as an adjunct therapy in Category II pulmonary tuberculosis in a randomized trial.Sci Rep. 2017 Jun 13;7(1):3354. doi: 10.1038/s41598-017-03514-1.
• [19] 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.