Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9YXZSO)

• DOT Name: H(+)/Cl(-) exchange transporter 5 (CLCN5)
• Synonyms: Chloride channel protein 5; ClC-5; Chloride transporter ClC-5
• Gene Name: CLCN5
• Related Disease:
  Classic lissencephaly
  Dent disease type 1
  Intellectual disability
  Bartter syndrome
  Chronic renal failure
  Dent disease type 2
  End-stage renal disease
  Glomerulosclerosis
  Hepatitis C virus infection
  Hypophosphatemic rickets
  Inflammatory bowel disease
  Interstitial nephritis
  Irritable bowel syndrome
  Kidney failure
  Nephrocalcinosis
  Nephropathy
  Oculocerebrorenal syndrome
  Osteoporosis
  Renal fibrosis
  Rickets
  Vitamin D-dependent rickets, type 2
  Goiter
  Plasma cell myeloma
  Renal tubular transport disease
  Small lymphocytic lymphoma
  Chronic kidney disease
  Familial primary hypomagnesemia
  Glioma
  Malignant glioma
  Membranous glomerulonephritis
  Mixed glioma
  Non-insulin dependent diabetes
  Renal tubule disorder
• UniProt ID: CLCN5_HUMAN
• PDB ID: 2J9L; 2JA3
• Pfam ID: PF00571 ; PF00654
• Sequence:
  MAMWQGAMDNRGFQQGSFSSFQNSSSDEDLMDIPATAMDFSMRDDVPPLDREVGEDKSYN
  GGGIGSSNRIMDFLEEPIPGVGTYDDFNTIDWVREKSRDRDRHREITNKSKESTWALIHS
  VSDAFSGWLLMLLIGLLSGSLAGLIDISAHWMTDLKEGICTGGFWFNHEHCCWNSEHVTF
  EERDKCPEWNSWSQLIISTDEGAFAYIVNYFMYVLWALLFAFLAVSLVKVFAPYACGSGI
  PEIKTILSGFIIRGYLGKWTLVIKTITLVLAVSSGLSLGKEGPLVHVACCCGNILCHCFN
  KYRKNEAKRREVLSAAAAAGVSVAFGAPIGGVLFSLEEVSYYFPLKTLWRSFFAALVAAF
  TLRSINPFGNSRLVLFYVEFHTPWHLFELVPFILLGIFGGLWGALFIRTNIAWCRKRKTT
  QLGKYPVIEVLVVTAITAILAFPNEYTRMSTSELISELFNDCGLLDSSKLCDYENRFNTS
  KGGELPDRPAGVGVYSAMWQLALTLILKIVITIFTFGMKIPSGLFIPSMAVGAIAGRLLG
  VGMEQLAYYHQEWTVFNSWCSQGADCITPGLYAMVGAAACLGGVTRMTVSLVVIMFELTG
  GLEYIVPLMAAAMTSKWVADALGREGIYDAHIRLNGYPFLEAKEEFAHKTLAMDVMKPRR
  NDPLLTVLTQDSMTVEDVETIISETTYSGFPVVVSRESQRLVGFVLRRDLIISIENARKK
  QDGVVSTSIIYFTEHSPPLPPYTPPTLKLRNILDLSPFTVTDLTPMEIVVDIFRKLGLRQ
  CLVTHNGRLLGIITKKDVLKHIAQMANQDPDSILFN
• Function: Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels (Probable).
• Tissue Specificity: Kidney. Moderately expressed in aortic vascular smooth muscle and endothelial cells, and at a slightly higher level in the coronary vascular smooth muscle.
• KEGG Pathway: Neutrophil extracellular trap formation (hsa04613)
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic lissencephaly	DISR8S3S	Definitive	Biomarker	[1]
Dent disease type 1	DISNGJIQ	Definitive	X-linked	[2]
Intellectual disability	DISMBNXP	Definitive	Biomarker	[3]
Bartter syndrome	DIS7D44B	Strong	Genetic Variation	[4]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[5]
Dent disease type 2	DISJFNHL	Strong	Biomarker	[6]
End-stage renal disease	DISXA7GG	Strong	Genetic Variation	[5]
Glomerulosclerosis	DISJF20Z	Strong	Genetic Variation	[7]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[8]
Hypophosphatemic rickets	DIS7XTW5	Strong	Biomarker	[9]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[10]
Interstitial nephritis	DISKQGND	Strong	Genetic Variation	[11]
Irritable bowel syndrome	DIS27206	Strong	Altered Expression	[10]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[12]
Nephrocalcinosis	DIS5ZVJP	Strong	Genetic Variation	[13]
Nephropathy	DISXWP4P	Strong	Altered Expression	[14]
Oculocerebrorenal syndrome	DIS8TEDY	Strong	Biomarker	[15]
Osteoporosis	DISF2JE0	Strong	Biomarker	[16]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[17]
Rickets	DISH89YF	Strong	Biomarker	[18]
Vitamin D-dependent rickets, type 2	DISZHFC3	Strong	Biomarker	[9]
Goiter	DISLCGI6	moderate	Biomarker	[19]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[20]
Renal tubular transport disease	DISBGF8S	moderate	Biomarker	[21]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[22]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[17]
Familial primary hypomagnesemia	DIS6TTKI	Limited	Genetic Variation	[23]
Glioma	DIS5RPEH	Limited	Biomarker	[24]
Malignant glioma	DISFXKOV	Limited	Biomarker	[24]
Membranous glomerulonephritis	DISFSUKQ	Limited	Biomarker	[14]
Mixed glioma	DIS64UY3	Limited	Biomarker	[24]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[14]
Renal tubule disorder	DISAFXMQ	Limited	Genetic Variation	[25]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[36]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[30]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[31]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[32]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[33]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[34]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[35]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[37]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of H(+)/Cl(-) exchange transporter 5 (CLCN5).	[41]

References

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