Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHG60RE)

• DOT Name: Collagen alpha-5(IV) chain (COL4A5)
• Synonyms: Collagen alpha-5(IV) chain
• Gene Name: COL4A5
• Related Disease:
  Alport syndrome
  Pneumonia
  Retinopathy
  Rheumatoid arthritis
  Vascular purpura
  X-linked Alport syndrome
  X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
  Acute respiratory failure
  Adult respiratory distress syndrome
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Chondrosarcoma
  Chronic renal failure
  Colorectal neoplasm
  Deafness
  Dermatomyositis
  Diabetic kidney disease
  Early-onset anterior polar cataract
  End-stage renal disease
  Epilepsy
  Focal segmental glomerulosclerosis
  Glomerulonephritis
  Glomerulosclerosis
  Hematuria, benign familial
  Hereditary nephritis
  IgA nephropathy
  Kidney failure
  Leiomyoma
  Long QT syndrome
  Lung adenocarcinoma
  Lung carcinoma
  Minimally invasive lung adenocarcinoma
  Neoplasm
  Nephritis
  Uterine fibroids
  Adenocarcinoma
  Arrhythmia
  Arterial tortuosity syndrome
  Chronic kidney disease
  Lung cancer
  Trichohepatoenteric syndrome
  Non-insulin dependent diabetes
  Asthma
  Intellectual disability
  Nephrotic syndrome
  Sensorineural hearing loss disorder
  T-cell acute lymphoblastic leukaemia
• UniProt ID: CO4A5_HUMAN
• PDB ID: 5NAZ; 6WKU
• Pfam ID: PF01413 ; PF01391
• Sequence:
  MKLRGVSLAAGLFLLALSLWGQPAEAAACYGCSPGSKCDCSGIKGEKGERGFPGLEGHPG
  LPGFPGPEGPPGPRGQKGDDGIPGPPGPKGIRGPPGLPGFPGTPGLPGMPGHDGAPGPQG
  IPGCNGTKGERGFPGSPGFPGLQGPPGPPGIPGMKGEPGSIIMSSLPGPKGNPGYPGPPG
  IQGLPGPTGIPGPIGPPGPPGLMGPPGPPGLPGPKGNMGLNFQGPKGEKGEQGLQGPPGP
  PGQISEQKRPIDVEFQKGDQGLPGDRGPPGPPGIRGPPGPPGGEKGEKGEQGEPGKRGKP
  GKDGENGQPGIPGLPGDPGYPGEPGRDGEKGQKGDTGPPGPPGLVIPRPGTGITIGEKGN
  IGLPGLPGEKGERGFPGIQGPPGLPGPPGAAVMGPPGPPGFPGERGQKGDEGPPGISIPG
  PPGLDGQPGAPGLPGPPGPAGPHIPPSDEICEPGPPGPPGSPGDKGLQGEQGVKGDKGDT
  CFNCIGTGISGPPGQPGLPGLPGPPGSLGFPGQKGEKGQAGATGPKGLPGIPGAPGAPGF
  PGSKGEPGDILTFPGMKGDKGELGSPGAPGLPGLPGTPGQDGLPGLPGPKGEPGGITFKG
  ERGPPGNPGLPGLPGNIGPMGPPGFGPPGPVGEKGIQGVAGNPGQPGIPGPKGDPGQTIT
  QPGKPGLPGNPGRDGDVGLPGDPGLPGQPGLPGIPGSKGEPGIPGIGLPGPPGPKGFPGI
  PGPPGAPGTPGRIGLEGPPGPPGFPGPKGEPGFALPGPPGPPGLPGFKGALGPKGDRGFP
  GPPGPPGRTGLDGLPGPKGDVGPNGQPGPMGPPGLPGIGVQGPPGPPGIPGPIGQPGLHG
  IPGEKGDPGPPGLDVPGPPGERGSPGIPGAPGPIGPPGSPGLPGKAGASGFPGTKGEMGM
  MGPPGPPGPLGIPGRSGVPGLKGDDGLQGQPGLPGPTGEKGSKGEPGLPGPPGPMDPNLL
  GSKGEKGEPGLPGIPGVSGPKGYQGLPGDPGQPGLSGQPGLPGPPGPKGNPGLPGQPGLI
  GPPGLKGTIGDMGFPGPQGVEGPPGPSGVPGQPGSPGLPGQKGDKGDPGISSIGLPGLPG
  PKGEPGLPGYPGNPGIKGSVGDPGLPGLPGTPGAKGQPGLPGFPGTPGPPGPKGISGPPG
  NPGLPGEPGPVGGGGHPGQPGPPGEKGKPGQDGIPGPAGQKGEPGQPGFGNPGPPGLPGL
  SGQKGDGGLPGIPGNPGLPGPKGEPGFHGFPGVQGPPGPPGSPGPALEGPKGNPGPQGPP
  GRPGLPGPEGPPGLPGNGGIKGEKGNPGQPGLPGLPGLKGDQGPPGLQGNPGRPGLNGMK
  GDPGLPGVPGFPGMKGPSGVPGSAGPEGEPGLIGPPGPPGLPGPSGQSIIIKGDAGPPGI
  PGQPGLKGLPGPQGPQGLPGPTGPPGDPGRNGLPGFDGAGGRKGDPGLPGQPGTRGLDGP
  PGPDGLQGPPGPPGTSSVAHGFLITRHSQTTDAPQCPQGTLQVYEGFSLLYVQGNKRAHG
  QDLGTAGSCLRRFSTMPFMFCNINNVCNFASRNDYSYWLSTPEPMPMSMQPLKGQSIQPF
  ISRCAVCEAPAVVIAVHSQTIQIPHCPQGWDSLWIGYSFMMHTSAGAEGSGQALASPGSC
  LEEFRSAPFIECHGRGTCNYYANSYSFWLATVDVSDMFSKPQSETLKAGDLRTRISRCQV
  CMKRT
• Function: Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.
• Tissue Specificity: Isoform 2 is found in kidney.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Cytoskeleton in muscle cells (hsa04820)
  Relaxin sig.ling pathway (hsa04926)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Protein digestion and absorption (hsa04974)
  Amoebiasis (hsa05146)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
• Reactome Pathway:
  Extracellular matrix organization (R-HSA-1474244)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Signaling by PDGF (R-HSA-186797)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  Integrin cell surface interactions (R-HSA-216083)
  Anchoring fibril formation (R-HSA-2214320)
  Crosslinking of collagen fibrils (R-HSA-2243919)
  Laminin interactions (R-HSA-3000157)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  ECM proteoglycans (R-HSA-3000178)
  NCAM1 interactions (R-HSA-419037)
  Collagen chain trimerization (R-HSA-8948216)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alport syndrome	DIS25AB4	Definitive	X-linked	[1]
Pneumonia	DIS8EF3M	Definitive	Biomarker	[2]
Retinopathy	DISB4B0F	Definitive	Genetic Variation	[3]
Rheumatoid arthritis	DISTSB4J	Definitive	Genetic Variation	[4]
Vascular purpura	DIS6ZZMF	Definitive	Biomarker	[5]
X-linked Alport syndrome	DISBWRMJ	Definitive	X-linked	[1]
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius	DIS6QXIR	Definitive	Genetic Variation	[6]
Acute respiratory failure	DIS5KQ5Y	Strong	Biomarker	[7]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[10]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[10]
Chondrosarcoma	DIS4I7JB	Strong	Altered Expression	[11]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[12]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[13]
Deafness	DISKCLH4	Strong	Biomarker	[14]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[15]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[16]
Early-onset anterior polar cataract	DISTOPIY	Strong	Biomarker	[2]
End-stage renal disease	DISXA7GG	Strong	Genetic Variation	[12]
Epilepsy	DISBB28L	Strong	Genetic Variation	[17]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[18]
Glomerulonephritis	DISPZIQ3	Strong	Genetic Variation	[19]
Glomerulosclerosis	DISJF20Z	Strong	Genetic Variation	[20]
Hematuria, benign familial	DISCWU1L	Strong	Genetic Variation	[21]
Hereditary nephritis	DISECBR1	Strong	Biomarker	[22]
IgA nephropathy	DISZ8MTK	Strong	Altered Expression	[23]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[24]
Leiomyoma	DISLDDFN	Strong	Genetic Variation	[25]
Long QT syndrome	DISMKWS3	Strong	Biomarker	[26]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[27]
Lung carcinoma	DISTR26C	Strong	Biomarker	[28]
Minimally invasive lung adenocarcinoma	DIS4W83X	Strong	Altered Expression	[29]
Neoplasm	DISZKGEW	Strong	Biomarker	[30]
Nephritis	DISQZQ70	Strong	Genetic Variation	[31]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[32]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[33]
Arrhythmia	DISFF2NI	moderate	Genetic Variation	[34]
Arterial tortuosity syndrome	DISWG36B	moderate	Genetic Variation	[35]
Chronic kidney disease	DISW82R7	moderate	Genetic Variation	[36]
Lung cancer	DISCM4YA	moderate	Biomarker	[28]
Trichohepatoenteric syndrome	DISL3ODF	moderate	Biomarker	[34]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[37]
Asthma	DISW9QNS	Limited	Genetic Variation	[38]
Intellectual disability	DISMBNXP	Limited	Biomarker	[39]
Nephrotic syndrome	DISSPSC2	Limited	Genetic Variation	[40]
Sensorineural hearing loss disorder	DISJV45Z	Limited	Biomarker	[41]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Altered Expression	[42]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Collagen alpha-5(IV) chain (COL4A5) affects the response to substance of Cisplatin.	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Collagen alpha-5(IV) chain (COL4A5).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Collagen alpha-5(IV) chain (COL4A5).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Collagen alpha-5(IV) chain (COL4A5).	[56]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the methylation of Collagen alpha-5(IV) chain (COL4A5).	[57]

11 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 Collagen alpha-5(IV) chain (COL4A5).	[44]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Collagen alpha-5(IV) chain (COL4A5).	[45]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-5(IV) chain (COL4A5).	[46]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Collagen alpha-5(IV) chain (COL4A5).	[47]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Collagen alpha-5(IV) chain (COL4A5).	[48]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Collagen alpha-5(IV) chain (COL4A5).	[49]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Collagen alpha-5(IV) chain (COL4A5).	[50]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Collagen alpha-5(IV) chain (COL4A5).	[51]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Collagen alpha-5(IV) chain (COL4A5).	[52]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Collagen alpha-5(IV) chain (COL4A5).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Collagen alpha-5(IV) chain (COL4A5).	[55]

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