Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5E59C8)

• DOT Name: Collagen alpha-1(II) chain (COL2A1)
• Synonyms: Alpha-1 type II collagen
• Gene Name: COL2A1
• Related Disease:
  Achondrogenesis type II
  Bone resorption
  Disorder of orbital region
  Kniest dysplasia
  Platyspondylic dysplasia, Torrance type
  Spondyloepimetaphyseal dysplasia, Strudwick type
  Spondyloepiphyseal dysplasia congenita
  Spondyloepiphyseal dysplasia with metatarsal shortening
  Spondylometaphyseal dysplasia
  Spondyloperipheral dysplasia
  Stickler syndrome type 1
  Stickler syndrome, type I, nonsyndromic ocular
  Arthritis
  Avascular necrosis of femoral head, primary, 1
  Cataract
  Chondrosarcoma
  Hypothyroidism
  Legg-Calve-Perthes disease
  Melanoma
  Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
  Otospondylomegaepiphyseal dysplasia, autosomal recessive
  Spondyloepiphyseal dysplasia
  Spondyloepiphyseal dysplasia tarda, X-linked
  Spondylometaphyseal dysplasia, 'corner fracture' type
  Synovitis
  Wagner disease
  Cataract 20 multiple types
  Hyperplasia
  Multiple epiphyseal dysplasia
  Myopia
  Sensorineural hearing loss disorder
  Spondyloepimetaphyseal dysplasia
  Spondyloepiphyseal dysplasia, Stanescu type
  Autosomal dominant rhegmatogenous retinal detachment
  Dysspondyloenchondromatosis
  Familial avascular necrosis of femoral head
  Hypochondrogenesis
  Multiple epiphyseal dysplasia, Beighton type
  Spondylometaphyseal dysplasia, Schmidt type
  Fetal growth restriction
  Hyperostosis corticalis generalisata
  Isolated cleft palate
  Melnick-Needles syndrome
  Osteochondrodysplasia
  Otospondylomegaepiphyseal dysplasia
  Schwartz-Jampel syndrome
  Schwartz-Jampel syndrome type 1
  Vitreoretinopathy with phalangeal epiphyseal dysplasia
• UniProt ID: CO2A1_HUMAN
• PDB ID: 1U5M; 2FSE; 2SEB; 5NIR; 5OCX; 5OCY; 6BIN; 6HG7; 6NIX; 7NZE
• Pfam ID: PF01410 ; PF01391 ; PF00093
• Sequence:
  MIRLGAPQTLVLLTLLVAAVLRCQGQDVQEAGSCVQDGQRYNDKDVWKPEPCRICVCDTG
  TVLCDDIICEDVKDCLSPEIPFGECCPICPTDLATASGQPGPKGQKGEPGDIKDIVGPKG
  PPGPQGPAGEQGPRGDRGDKGEKGAPGPRGRDGEPGTPGNPGPPGPPGPPGPPGLGGNFA
  AQMAGGFDEKAGGAQLGVMQGPMGPMGPRGPPGPAGAPGPQGFQGNPGEPGEPGVSGPMG
  PRGPPGPPGKPGDDGEAGKPGKAGERGPPGPQGARGFPGTPGLPGVKGHRGYPGLDGAKG
  EAGAPGVKGESGSPGENGSPGPMGPRGLPGERGRTGPAGAAGARGNDGQPGPAGPPGPVG
  PAGGPGFPGAPGAKGEAGPTGARGPEGAQGPRGEPGTPGSPGPAGASGNPGTDGIPGAKG
  SAGAPGIAGAPGFPGPRGPPGPQGATGPLGPKGQTGEPGIAGFKGEQGPKGEPGPAGPQG
  APGPAGEEGKRGARGEPGGVGPIGPPGERGAPGNRGFPGQDGLAGPKGAPGERGPSGLAG
  PKGANGDPGRPGEPGLPGARGLTGRPGDAGPQGKVGPSGAPGEDGRPGPPGPQGARGQPG
  VMGFPGPKGANGEPGKAGEKGLPGAPGLRGLPGKDGETGAAGPPGPAGPAGERGEQGAPG
  PSGFQGLPGPPGPPGEGGKPGDQGVPGEAGAPGLVGPRGERGFPGERGSPGAQGLQGPRG
  LPGTPGTDGPKGASGPAGPPGAQGPPGLQGMPGERGAAGIAGPKGDRGDVGEKGPEGAPG
  KDGGRGLTGPIGPPGPAGANGEKGEVGPPGPAGSAGARGAPGERGETGPPGPAGFAGPPG
  ADGQPGAKGEQGEAGQKGDAGAPGPQGPSGAPGPQGPTGVTGPKGARGAQGPPGATGFPG
  AAGRVGPPGSNGNPGPPGPPGPSGKDGPKGARGDSGPPGRAGEPGLQGPAGPPGEKGEPG
  DDGPSGAEGPPGPQGLAGQRGIVGLPGQRGERGFPGLPGPSGEPGKQGAPGASGDRGPPG
  PVGPPGLTGPAGEPGREGSPGADGPPGRDGAAGVKGDRGETGAVGAPGAPGPPGSPGPAG
  PTGKQGDRGEAGAQGPMGPSGPAGARGIQGPQGPRGDKGEAGEPGERGLKGHRGFTGLQG
  LPGPPGPSGDQGASGPAGPSGPRGPPGPVGPSGKDGANGIPGPIGPPGPRGRSGETGPAG
  PPGNPGPPGPPGPPGPGIDMSAFAGLGPREKGPDPLQYMRADQAAGGLRQHDAEVDATLK
  SLNNQIESIRSPEGSRKNPARTCRDLKLCHPEWKSGDYWIDPNQGCTLDAMKVFCNMETG
  ETCVYPNPANVPKKNWWSSKSKEKKHIWFGETINGGFHFSYGDDNLAPNTANVQMTFLRL
  LSTEGSQNITYHCKNSIAYLDEAAGNLKKALLIQGSNDVEIRAEGNSRFTYTALKDGCTK
  HTGKWGKTVIEYRSQKTSRLPIIDIAPMDIGGPEQEFGVDIGPVCFL
• Function: Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces.
• Tissue Specificity: Isoform 2 is highly expressed in juvenile chondrocyte and low in fetal chondrocyte.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Protein digestion and absorption (hsa04974)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  Extracellular matrix organization (R-HSA-1474244)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Signaling by PDGF (R-HSA-186797)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  Integrin cell surface interactions (R-HSA-216083)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  ECM proteoglycans (R-HSA-3000178)
  NCAM1 interactions (R-HSA-419037)
  MET activates PTK2 signaling (R-HSA-8874081)
  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
Achondrogenesis type II	DIS7IMR5	Definitive	Autosomal dominant	[1]
Bone resorption	DISGSZ65	Definitive	Biomarker	[2]
Disorder of orbital region	DISH0ECJ	Definitive	Biomarker	[3]
Kniest dysplasia	DISCHQ9R	Definitive	Autosomal dominant	[1]
Platyspondylic dysplasia, Torrance type	DIS1NJHF	Definitive	Autosomal dominant	[1]
Spondyloepimetaphyseal dysplasia, Strudwick type	DISNRAF6	Definitive	Autosomal dominant	[4]
Spondyloepiphyseal dysplasia congenita	DISLC6W8	Definitive	Autosomal dominant	[1]
Spondyloepiphyseal dysplasia with metatarsal shortening	DISPOUCA	Definitive	Autosomal dominant	[5]
Spondylometaphyseal dysplasia	DISDTAJK	Definitive	Autosomal dominant	[1]
Spondyloperipheral dysplasia	DISAXS3D	Definitive	Autosomal dominant	[1]
Stickler syndrome type 1	DIST5L4S	Definitive	Autosomal dominant	[1]
Stickler syndrome, type I, nonsyndromic ocular	DIST3E07	Definitive	Autosomal dominant	[6]
Arthritis	DIST1YEL	Strong	Biomarker	[7]
Avascular necrosis of femoral head, primary, 1	DISJMQ4T	Strong	Autosomal dominant	[8]
Cataract	DISUD7SL	Strong	Biomarker	[9]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[10]
Hypothyroidism	DISR0H6D	Strong	Therapeutic	[11]
Legg-Calve-Perthes disease	DISE7BRZ	Strong	Autosomal dominant	[8]
Melanoma	DIS1RRCY	Strong	Biomarker	[12]
Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis	DISDEM11	Strong	Autosomal dominant	[13]
Otospondylomegaepiphyseal dysplasia, autosomal recessive	DISGKOCR	Strong	Autosomal recessive	[14]
Spondyloepiphyseal dysplasia	DIS1JG9A	Strong	Genetic Variation	[15]
Spondyloepiphyseal dysplasia tarda, X-linked	DIS9EL3M	Strong	Genetic Variation	[16]
Spondylometaphyseal dysplasia, 'corner fracture' type	DIS2MS2B	Strong	Genetic Variation	[17]
Synovitis	DISW2GPY	Strong	Biomarker	[18]
Wagner disease	DISAJ1K0	Strong	Genetic Variation	[19]
Cataract 20 multiple types	DISN0IHS	moderate	Biomarker	[9]
Hyperplasia	DISK4DFB	moderate	Biomarker	[20]
Multiple epiphyseal dysplasia	DIS5FZLR	moderate	Biomarker	[21]
Myopia	DISK5S60	moderate	Genetic Variation	[22]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Altered Expression	[23]
Spondyloepimetaphyseal dysplasia	DISO4L5A	moderate	Biomarker	[24]
Spondyloepiphyseal dysplasia, Stanescu type	DISWY1VQ	Moderate	Autosomal dominant	[1]
Autosomal dominant rhegmatogenous retinal detachment	DISVAMM4	Supportive	Autosomal dominant	[25]
Dysspondyloenchondromatosis	DISLRVIC	Supportive	Autosomal dominant	[26]
Familial avascular necrosis of femoral head	DIS1X75T	Supportive	Autosomal dominant	[27]
Hypochondrogenesis	DIS0VDXA	Supportive	Autosomal dominant	[28]
Multiple epiphyseal dysplasia, Beighton type	DISVQ08J	Supportive	Autosomal dominant	[29]
Spondylometaphyseal dysplasia, Schmidt type	DISG1OAZ	Supportive	Autosomal dominant	[30]
Fetal growth restriction	DIS5WEJ5	Limited	Biomarker	[31]
Hyperostosis corticalis generalisata	DISR4BHB	Limited	Biomarker	[21]
Isolated cleft palate	DISV80CD	Limited	Biomarker	[32]
Melnick-Needles syndrome	DIS0KTGM	Limited	Biomarker	[21]
Osteochondrodysplasia	DIS9SPWW	Limited	Genetic Variation	[33]
Otospondylomegaepiphyseal dysplasia	DISFFHOF	Limited	Autosomal recessive	[5]
Schwartz-Jampel syndrome	DIS3HCR8	Limited	Biomarker	[21]
Schwartz-Jampel syndrome type 1	DIS42TKQ	Limited	Biomarker	[21]
Vitreoretinopathy with phalangeal epiphyseal dysplasia	DISTV1J8	Limited	Unknown	[34]

2 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-1(II) chain (COL2A1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-1(II) chain (COL2A1).	[52]

23 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-1(II) chain (COL2A1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Collagen alpha-1(II) chain (COL2A1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Collagen alpha-1(II) chain (COL2A1).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[39]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[40]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[41]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[42]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[43]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[41]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[44]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Collagen alpha-1(II) chain (COL2A1).	[45]
Alendronate	DMY2KX9	Approved	Alendronate decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[46]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[47]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[48]
Diacerein	DMN2Q5I	Phase 4	Diacerein increases the expression of Collagen alpha-1(II) chain (COL2A1).	[49]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[50]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Collagen alpha-1(II) chain (COL2A1).	[51]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Collagen alpha-1(II) chain (COL2A1).	[49]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Collagen alpha-1(II) chain (COL2A1).	[54]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-1(II) chain (COL2A1).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Collagen alpha-1(II) chain (COL2A1).	[56]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Collagen alpha-1(II) chain (COL2A1).	[57]

References

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