Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC4G2YC)

• DOT Name: Collagen alpha-1(X) chain (COL10A1)
• Synonyms: Collagen alpha-1(X) chain
• Gene Name: COL10A1
• Related Disease:
  Breast carcinoma
  Pyle disease
  Schmid metaphyseal chondrodysplasia
  Advanced cancer
  Age-related macular degeneration
  Bladder cancer
  Breast cancer
  Breast neoplasm
  Colorectal carcinoma
  Ductal breast carcinoma in situ
  Inflammatory breast cancer
  Keloid
  Lung adenocarcinoma
  Morquio syndrome
  Non-small-cell lung cancer
  Oral cancer
  Osteoarthritis
  Progressive pseudorheumatoid arthropathy of childhood
  Spondyloepimetaphyseal dysplasia
  Urinary bladder cancer
  Urinary bladder neoplasm
  Achondroplasia
  Pseudoachondroplasia
  Skeletal dysplasia
  Spondyloepimetaphyseal dysplasia, Strudwick type
  Gastric cancer
  Macular corneal dystrophy
  Myopia
  Neoplasm
  Osteochondrodysplasia
  Stomach cancer
• UniProt ID: COAA1_HUMAN
• PDB ID: 1GR3
• Pfam ID: PF00386 ; PF01391
• Sequence:
  MLPQIPFLLLVSLNLVHGVFYAERYQMPTGIKGPLPNTKTQFFIPYTIKSKGIAVRGEQG
  TPGPPGPAGPRGHPGPSGPPGKPGYGSPGLQGEPGLPGPPGPSAVGKPGVPGLPGKPGER
  GPYGPKGDVGPAGLPGPRGPPGPPGIPGPAGISVPGKPGQQGPTGAPGPRGFPGEKGAPG
  VPGMNGQKGEMGYGAPGRPGERGLPGPQGPTGPSGPPGVGKRGENGVPGQPGIKGDRGFP
  GEMGPIGPPGPQGPPGERGPEGIGKPGAAGAPGQPGIPGTKGLPGAPGIAGPPGPPGFGK
  PGLPGLKGERGPAGLPGGPGAKGEQGPAGLPGKPGLTGPPGNMGPQGPKGIPGSHGLPGP
  KGETGPAGPAGYPGAKGERGSPGSDGKPGYPGKPGLDGPKGNPGLPGPKGDPGVGGPPGL
  PGPVGPAGAKGMPGHNGEAGPRGAPGIPGTRGPIGPPGIPGFPGSKGDPGSPGPPGPAGI
  ATKGLNGPTGPPGPPGPRGHSGEPGLPGPPGPPGPPGQAVMPEGFIKAGQRPSLSGTPLV
  SANQGVTGMPVSAFTVILSKAYPAIGTPIPFDKILYNRQQHYDPRTGIFTCQIPGIYYFS
  YHVHVKGTHVWVGLYKNGTPVMYTYDEYTKGYLDQASGSAIIDLTENDQVWLQLPNAESN
  GLYSSEYVHSSFSGFLVAPM
• Function: Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  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)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Pyle disease	DISJ2YQ3	Definitive	Biomarker	[2]
Schmid metaphyseal chondrodysplasia	DISX2EGR	Definitive	Autosomal dominant	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[5]
Bladder cancer	DISUHNM0	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Biomarker	[9]
Inflammatory breast cancer	DIS3QRWA	Strong	Altered Expression	[9]
Keloid	DISV09JY	Strong	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[11]
Morquio syndrome	DIS2Y2P2	Strong	Biomarker	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[13]
Oral cancer	DISLD42D	Strong	Biomarker	[14]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[15]
Progressive pseudorheumatoid arthropathy of childhood	DISBMRIW	Strong	Genetic Variation	[16]
Spondyloepimetaphyseal dysplasia	DISO4L5A	Strong	Biomarker	[17]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[6]
Achondroplasia	DISYWN2O	moderate	Genetic Variation	[18]
Pseudoachondroplasia	DISVJW4A	moderate	Genetic Variation	[18]
Skeletal dysplasia	DIS5Z8U6	moderate	Altered Expression	[19]
Spondyloepimetaphyseal dysplasia, Strudwick type	DISNRAF6	moderate	Genetic Variation	[20]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[21]
Macular corneal dystrophy	DISOLD0H	Limited	Genetic Variation	[22]
Myopia	DISK5S60	Limited	Genetic Variation	[23]
Neoplasm	DISZKGEW	Limited	Biomarker	[24]
Osteochondrodysplasia	DIS9SPWW	Limited	Altered Expression	[19]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Collagen alpha-1(X) chain (COL10A1).	[25]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Collagen alpha-1(X) chain (COL10A1).	[26]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Collagen alpha-1(X) chain (COL10A1).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Collagen alpha-1(X) chain (COL10A1).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Collagen alpha-1(X) chain (COL10A1).	[29]

References

• [1] Extracellular matrix proteins as diagnostic markers of breast carcinoma.J Cell Physiol. 2018 Aug;233(8):6280-6290. doi: 10.1002/jcp.26513. Epub 2018 Mar 9.
• [2] Spondylar dysplasia in type X collagenopathy.Pediatr Radiol. 2001 Feb;31(2):76-80. doi: 10.1007/s002470000394.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] High expression of COL10A1 is associated with poor prognosis in colorectal cancer.Onco Targets Ther. 2018 Mar 20;11:1571-1581. doi: 10.2147/OTT.S160196. eCollection 2018.
• [5] Seven new loci associated with age-related macular degeneration.Nat Genet. 2013 Apr;45(4):433-9, 439e1-2. doi: 10.1038/ng.2578. Epub 2013 Mar 3.
• [6] Risk score based on three mRNA expression predicts the survival of bladder cancer.Oncotarget. 2017 Jun 27;8(37):61583-61591. doi: 10.18632/oncotarget.18642. eCollection 2017 Sep 22.
• [7] MMP13 is potentially a new tumor marker for breast cancer diagnosis.Oncol Rep. 2009 Nov;22(5):1119-27. doi: 10.3892/or_00000544.
• [8] COL10A1 expression is elevated in diverse solid tumor types and is associated with tumor vasculature.Future Oncol. 2012 Aug;8(8):1031-40. doi: 10.2217/fon.12.79.
• [9] Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers.BMC Med Genomics. 2018 Sep 20;11(1):80. doi: 10.1186/s12920-018-0403-5.
• [10] Aberrant connective tissue differentiation towards cartilage and bone underlies human keloids in African Americans.Exp Dermatol. 2017 Aug;26(8):721-727. doi: 10.1111/exd.13271. Epub 2017 Feb 28.
• [11] Secreted phosphoprotein 1 upstream invasive network construction and analysis of lung adenocarcinoma compared with human normal adjacent tissues by integrative biocomputation.Cell Biochem Biophys. 2010 Apr;56(2-3):59-71. doi: 10.1007/s12013-009-9071-6.
• [12] Mutations in the N-terminal globular domain of the type X collagen gene (COL10A1) in patients with Schmid metaphyseal chondrodysplasia.Hum Mutat. 1997;9(2):131-5. doi: 10.1002/(SICI)1098-1004(1997)9:2<131::AID-HUMU5>3.0.CO;2-C.
• [13] MiR-384 induces apoptosis and autophagy of non-small cell lung cancer cells through the negative regulation of Collagen -1(X) chain gene.Biosci Rep. 2019 Feb 1;39(2):BSR20181523. doi: 10.1042/BSR20181523. Print 2019 Feb 28.
• [14] Exosomes derived from microRNA-101-3p-overexpressing human bone marrow mesenchymal stem cells suppress oral cancer cell proliferation, invasion, and migration.Mol Cell Biochem. 2019 Aug;458(1-2):11-26. doi: 10.1007/s11010-019-03526-7. Epub 2019 Jun 4.
• [15] Targeting -catenin dependent Wnt signaling via peptidomimetic inhibitors in murine chondrocytes and OA cartilage.Osteoarthritis Cartilage. 2018 Jun;26(6):818-823. doi: 10.1016/j.joca.2018.02.908. Epub 2018 Mar 17.
• [16] Assignment of gene responsible for progressive pseudorheumatoid dysplasia to chromosome 6 and examination of COL10A1 as candidate gene.Eur J Hum Genet. 1998 May-Jun;6(3):251-6. doi: 10.1038/sj.ejhg.5200187.
• [17] Linkage studies of a Missouri kindred with autosomal dominant spondyloepimetaphyseal dysplasia (SEMD) indicate genetic heterogeneity.J Bone Miner Res. 1997 Aug;12(8):1204-9. doi: 10.1359/jbmr.1997.12.8.1204.
• [18] SSCP and segregation analysis of the human type X collagen gene (COL10A1) in heritable forms of chondrodysplasia.Am J Hum Genet. 1992 Oct;51(4):841-9.
• [19] Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.J Clin Invest. 2017 Oct 2;127(10):3861-3865. doi: 10.1172/JCI93094. Epub 2017 Sep 18.
• [20] A novel sequence variant in COL10A1 causing spondylometaphyseal dysplasia accompanied with coxa valga: A case report.Medicine (Baltimore). 2019 Jul;98(30):e16485. doi: 10.1097/MD.0000000000016485.
• [21] TGF-1-SOX9 axis-inducible COL10A1 promotes invasion and metastasis in gastric cancer via epithelial-to-mesenchymal transition.Cell Death Dis. 2018 Aug 28;9(9):849. doi: 10.1038/s41419-018-0877-2.
• [22] RMRP mutations in cartilage-hair hypoplasia.Am J Med Genet A. 2006 Oct 1;140(19):2121-30. doi: 10.1002/ajmg.a.31331.
• [23] Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
• [24] Bioinformatics approach reveals systematic mechanism underlying lung adenocarcinoma.Tumori. 2015 May-Jun;101(3):281-6. doi: 10.5301/tj.5000278. Epub 2015 May 21.
• [25] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [26] Parathyroid hormone 1-34 reduces dexamethasone-induced terminal differentiation in human articular chondrocytes. Toxicology. 2016 Aug 10;368-369:116-128.
• [27] Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt/-catenin signaling pathway. Toxicol Lett. 2016 Jan 5;240(1):68-80. doi: 10.1016/j.toxlet.2015.10.007. Epub 2015 Oct 22.
• [28] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [29] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.