Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL6D1YE)

• DOT Name: Collagen alpha-1(IV) chain (COL4A1)
• Synonyms: Collagen alpha-1(IV) chain
• Gene Name: COL4A1
• Related Disease:
  Brain small vessel disease 1 with or without ocular anomalies
  Neoplasm
  Rheumatoid arthritis
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome
  Axenfeld anomaly
  Breast neoplasm
  Cardiovascular disease
  Cataract
  Cerebral palsy
  Coronary atherosclerosis
  Coronary heart disease
  Dementia
  High blood pressure
  Microphthalmia
  Migraine disorder
  Myocardial infarction
  Myopathy
  Nephrotic syndrome
  Peripheral arterial disease
  Pulmonary hypertension
  Schizencephaly
  Stomach cancer
  Stroke
  Urinary bladder neoplasm
  Hemolytic anemia
  Leukodystrophy
  Melanoma
  Microangiopathy and leukoencephalopathy, pontine, autosomal dominant
  Movement disorder
  Porencephaly
  Familial porencephaly
  Muscular dystrophy-dystroglycanopathy, type A
  Obsolete pontine autosomal dominant microangiopathy with leukoencephalopathy
  Retinal arterial tortuosity
  Axenfeld-Rieger syndrome
  Axenfeld-Rieger syndrome type 1
  Axenfeld-Rieger syndrome type 3
  Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy
  Cerebrovascular disease
  Diabetic kidney disease
  Focal segmental glomerulosclerosis
  Gastric cancer
  Leukoencephalopathy with vanishing white matter
  Rieger anomaly
  Vascular disease
• UniProt ID: CO4A1_HUMAN
• PDB ID: 1LI1; 5NAX; 5NAY; 6MPX
• Pfam ID: PF01413 ; PF01391
• Sequence:
  MGPRLSVWLLLLPAALLLHEEHSRAAAKGGCAGSGCGKCDCHGVKGQKGERGLPGLQGVI
  GFPGMQGPEGPQGPPGQKGDTGEPGLPGTKGTRGPPGASGYPGNPGLPGIPGQDGPPGPP
  GIPGCNGTKGERGPLGPPGLPGFAGNPGPPGLPGMKGDPGEILGHVPGMLLKGERGFPGI
  PGTPGPPGLPGLQGPVGPPGFTGPPGPPGPPGPPGEKGQMGLSFQGPKGDKGDQGVSGPP
  GVPGQAQVQEKGDFATKGEKGQKGEPGFQGMPGVGEKGEPGKPGPRGKPGKDGDKGEKGS
  PGFPGEPGYPGLIGRQGPQGEKGEAGPPGPPGIVIGTGPLGEKGERGYPGTPGPRGEPGP
  KGFPGLPGQPGPPGLPVPGQAGAPGFPGERGEKGDRGFPGTSLPGPSGRDGLPGPPGSPG
  PPGQPGYTNGIVECQPGPPGDQGPPGIPGQPGFIGEIGEKGQKGESCLICDIDGYRGPPG
  PQGPPGEIGFPGQPGAKGDRGLPGRDGVAGVPGPQGTPGLIGQPGAKGEPGEFYFDLRLK
  GDKGDPGFPGQPGMPGRAGSPGRDGHPGLPGPKGSPGSVGLKGERGPPGGVGFPGSRGDT
  GPPGPPGYGPAGPIGDKGQAGFPGGPGSPGLPGPKGEPGKIVPLPGPPGAEGLPGSPGFP
  GPQGDRGFPGTPGRPGLPGEKGAVGQPGIGFPGPPGPKGVDGLPGDMGPPGTPGRPGFNG
  LPGNPGVQGQKGEPGVGLPGLKGLPGLPGIPGTPGEKGSIGVPGVPGEHGAIGPPGLQGI
  RGEPGPPGLPGSVGSPGVPGIGPPGARGPPGGQGPPGLSGPPGIKGEKGFPGFPGLDMPG
  PKGDKGAQGLPGITGQSGLPGLPGQQGAPGIPGFPGSKGEMGVMGTPGQPGSPGPVGAPG
  LPGEKGDHGFPGSSGPRGDPGLKGDKGDVGLPGKPGSMDKVDMGSMKGQKGDQGEKGQIG
  PIGEKGSRGDPGTPGVPGKDGQAGQPGQPGPKGDPGISGTPGAPGLPGPKGSVGGMGLPG
  TPGEKGVPGIPGPQGSPGLPGDKGAKGEKGQAGPPGIGIPGLRGEKGDQGIAGFPGSPGE
  KGEKGSIGIPGMPGSPGLKGSPGSVGYPGSPGLPGEKGDKGLPGLDGIPGVKGEAGLPGT
  PGPTGPAGQKGEPGSDGIPGSAGEKGEPGLPGRGFPGFPGAKGDKGSKGEVGFPGLAGSP
  GIPGSKGEQGFMGPPGPQGQPGLPGSPGHATEGPKGDRGPQGQPGLPGLPGPMGPPGLPG
  IDGVKGDKGNPGWPGAPGVPGPKGDPGFQGMPGIGGSPGITGSKGDMGPPGVPGFQGPKG
  LPGLQGIKGDQGDQGVPGAKGLPGPPGPPGPYDIIKGEPGLPGPEGPPGLKGLQGLPGPK
  GQQGVTGLVGIPGPPGIPGFDGAPGQKGEMGPAGPTGPRGFPGPPGPDGLPGSMGPPGTP
  SVDHGFLVTRHSQTIDDPQCPSGTKILYHGYSLLYVQGNERAHGQDLGTAGSCLRKFSTM
  PFLFCNINNVCNFASRNDYSYWLSTPEPMPMSMAPITGENIRPFISRCAVCEAPAMVMAV
  HSQTIQIPPCPSGWSSLWIGYSFVMHTSAGAEGSGQALASPGSCLEEFRSAPFIECHGRG
  TCNYYANAYSFWLATIERSEMFKKPTPSTLKAGELRTHVSRCQVCMRRT
• 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; Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation.
• Tissue Specificity: Highly expressed in placenta.
• 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)
  Scavenging by Class A Receptors (R-HSA-3000480)
  NCAM1 interactions (R-HSA-419037)
  Collagen chain trimerization (R-HSA-8948216)
  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
Brain small vessel disease 1 with or without ocular anomalies	DISJKAHD	Definitive	Autosomal dominant	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[3]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[3]
Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome	DISKKF3C	Strong	Autosomal dominant	[5]
Axenfeld anomaly	DIS15GVG	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Cataract	DISUD7SL	Strong	Genetic Variation	[9]
Cerebral palsy	DIS82ODL	Strong	Biomarker	[10]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[11]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[12]
Dementia	DISXL1WY	Strong	Genetic Variation	[13]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[14]
Microphthalmia	DISGEBES	Strong	Genetic Variation	[15]
Migraine disorder	DISFCQTG	Strong	Biomarker	[16]
Myocardial infarction	DIS655KI	Strong	Biomarker	[17]
Myopathy	DISOWG27	Strong	Genetic Variation	[18]
Nephrotic syndrome	DISSPSC2	Strong	Genetic Variation	[19]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[20]
Pulmonary hypertension	DIS1RSP5	Strong	Therapeutic	[21]
Schizencephaly	DISZVYEC	Strong	Genetic Variation	[22]
Stomach cancer	DISKIJSX	Strong	Biomarker	[23]
Stroke	DISX6UHX	Strong	Biomarker	[18]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[24]
Hemolytic anemia	DIS803XQ	moderate	Genetic Variation	[25]
Leukodystrophy	DISVY1TT	moderate	Genetic Variation	[26]
Melanoma	DIS1RRCY	moderate	Biomarker	[27]
Microangiopathy and leukoencephalopathy, pontine, autosomal dominant	DIS9LOSD	Moderate	Autosomal dominant	[28]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[29]
Porencephaly	DISXBWXN	moderate	Genetic Variation	[18]
Familial porencephaly	DISTLT56	Supportive	Autosomal dominant	[30]
Muscular dystrophy-dystroglycanopathy, type A	DISZTBC4	Supportive	Autosomal recessive	[31]
Obsolete pontine autosomal dominant microangiopathy with leukoencephalopathy	DISMDQJ6	Supportive	Autosomal dominant	[32]
Retinal arterial tortuosity	DISYUV7F	Supportive	Autosomal dominant	[33]
Axenfeld-Rieger syndrome	DIS6XY4L	Limited	Biomarker	[6]
Axenfeld-Rieger syndrome type 1	DISCJK7U	Limited	Biomarker	[6]
Axenfeld-Rieger syndrome type 3	DIS0YYSM	Limited	Biomarker	[6]
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy	DIS93Z3E	Limited	Genetic Variation	[34]
Cerebrovascular disease	DISAB237	Limited	Genetic Variation	[35]
Diabetic kidney disease	DISJMWEY	Limited	Biomarker	[36]
Focal segmental glomerulosclerosis	DISJNHH0	Limited	Biomarker	[37]
Gastric cancer	DISXGOUK	Limited	Biomarker	[23]
Leukoencephalopathy with vanishing white matter	DIS3J8NN	Limited	Biomarker	[6]
Rieger anomaly	DISNBLZ5	Limited	Biomarker	[6]
Vascular disease	DISVS67S	Limited	Genetic Variation	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Menadione	DMSJDTY	Approved	Collagen alpha-1(IV) chain (COL4A1) increases the Cytology abnormal ADR of Menadione.	[62]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Collagen alpha-1(IV) chain (COL4A1).	[46]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[47]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Collagen alpha-1(IV) chain (COL4A1).	[48]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[49]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Collagen alpha-1(IV) chain (COL4A1).	[50]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[51]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Collagen alpha-1(IV) chain (COL4A1).	[52]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Collagen alpha-1(IV) chain (COL4A1).	[53]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Collagen alpha-1(IV) chain (COL4A1).	[43]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[54]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[43]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[55]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Collagen alpha-1(IV) chain (COL4A1).	[56]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Collagen alpha-1(IV) chain (COL4A1).	[57]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[59]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Collagen alpha-1(IV) chain (COL4A1).	[61]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Collagen alpha-1(IV) chain (COL4A1).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Collagen alpha-1(IV) chain (COL4A1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-1(IV) chain (COL4A1).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collagen alpha-1(IV) chain (COL4A1).	[60]

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