Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM9IM6J)

• DOT Name: Collagen alpha-1(XIII) chain (COL13A1)
• Synonyms: COLXIIIA1
• Gene Name: COL13A1
• Related Disease:
  Advanced cancer
  Congenital myasthenic syndrome 19
  LambertEaton myasthenic syndrome
  Liver cirrhosis
  Myocardial infarction
  Non-alcoholic fatty liver disease
  Parkinson disease
  Urinary bladder neoplasm
  Bladder cancer
  Congenital myasthenic syndrome
  Urinary bladder cancer
  Obsolete presynaptic congenital myasthenic syndrome
  Postsynaptic congenital myasthenic syndrome
• UniProt ID: CODA1_HUMAN
• Pfam ID: PF01391
• Sequence:
  MVAERTHKAAATGARGPGELGAPGTVALVAARAERGARLPSPGSCGLLTLALCSLALSLL
  AHFRTAELQARVLRLEAERGEQQMETAILGRVNQLLDEKWKLHSRRRREAPKTSPGCNCP
  PGPPGPTGRPGLPGDKGAIGMPGRVGSPGDAGLSIIGPRGPPGQPGTRGFPGFPGPIGLD
  GKPGHPGPKGDMGLTGPPGQPGPQGQKGEKGQCGEYPHRECLSSMPAALRSSQIIALKLL
  PLLNSVRLAPPPVIKRRTFQGEQSQASIQGPPGPPGPPGPSGPLGHPGLPGPMGPPGLPG
  PPGPKGDPGIQGYHGRKGERGMPGMPGKHGAKGAPGIAVAGMKGEPGIPGTKGEKGAEGS
  PGLPGLLGQKGEKGDAGNSIGGGRGEPGPPGLPGPPGPKGEAGVDGQVGPPGQPGDKGER
  GAAGEQGPDGPKGSKGEPGKGEMVDYNGNINEALQEIRTLALMGPPGLPGQIGPPGAPGI
  PGQKGEIGLPGPPGHDGEKGPRGKPGDMGPPGPQGPPGKDGPPGVKGENGHPGSPGEKGE
  KGETGQAGSPGEKGEAGEKGNPGAEVPGLPGPEGPPGPPGLQGVPGPKGEAGLDGAKGEK
  GFQGEKGDRGPLGLPGASGLDGRPGPPGTPGPIGVPGPAGPKGERGSKGDPGMTGPTGAA
  GLPGLHGPPGDKGNRGERGKKGSRGPKGDKGDQGAPGLDAPCPLGEDGLPVQGCWNK
• Function: Involved in cell-matrix and cell-cell adhesion interactions that are required for normal development. May participate in the linkage between muscle fiber and basement membrane. May play a role in endochondral ossification of bone and branching morphogenesis of lung. Binds heparin. At neuromuscular junctions, may play a role in acetylcholine receptor clustering.
• Tissue Specificity: Widely expressed in both fetal and adult ocular tissues (at protein level). In the eye, expression is accentuated in the ciliary muscle, optic nerve and the neural retina. In early placenta, localized to fibroblastoid stromal cells of the placental villi, to endothelial cells of developing capillaries and to cells of the cytotrophoblastic columns. Also detected in large decidual cells of the decidual membrane and to stromal cells of the gestational endometrium, but not in the epithelial cells in the endometrial glands. Isoform 10: Expressed in muscle .
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
  Integrin cell surface interactions (R-HSA-216083)
  Collagen chain trimerization (R-HSA-8948216)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Congenital myasthenic syndrome 19	DIS9CV2D	Strong	Autosomal recessive	[2]
LambertEaton myasthenic syndrome	DISN0Q7Q	Strong	Genetic Variation	[3]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[4]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[5]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[4]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	moderate	Biomarker	[7]
Congenital myasthenic syndrome	DISJLG2T	moderate	Genetic Variation	[8]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[7]
Obsolete presynaptic congenital myasthenic syndrome	DISCATK3	Supportive	Autosomal dominant	[9]
Postsynaptic congenital myasthenic syndrome	DIS92VN2	Supportive	Autosomal recessive	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Collagen alpha-1(XIII) chain (COL13A1) decreases the response to substance of Simvastatin.	[32]

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(XIII) chain (COL13A1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collagen alpha-1(XIII) chain (COL13A1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Collagen alpha-1(XIII) chain (COL13A1).	[17]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[18]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[19]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[20]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Collagen alpha-1(XIII) chain (COL13A1).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[22]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[29]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[30]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Collagen alpha-1(XIII) chain (COL13A1).	[31]

References

• [1] Collagen type IV alpha 1 (COL4A1) and collagen type XIII alpha 1 (COL13A1) produced in cancer cells promote tumor budding at the invasion front in human urothelial carcinoma of the bladder.Oncotarget. 2017 May 30;8(22):36099-36114. doi: 10.18632/oncotarget.16432.
• [2] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [3] The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations. Brain. 2019 Jun 1;142(6):1547-1560. doi: 10.1093/brain/awz107.
• [4] Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.Gastroenterology. 2010 Nov;139(5):1567-76, 1576.e1-6. doi: 10.1053/j.gastro.2010.07.057. Epub 2010 Aug 11.
• [5] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [6] Parkinson disease loci in the mid-western Amish.Hum Genet. 2013 Nov;132(11):1213-21. doi: 10.1007/s00439-013-1316-1. Epub 2013 Jun 21.
• [7] Diagnostic and prognostic role of urinary collagens in primary human bladder cancer.Cancer Sci. 2017 Nov;108(11):2221-2228. doi: 10.1111/cas.13384. Epub 2017 Sep 15.
• [8] Congenital myasthenic syndrome caused by novel COL13A1 mutations.J Neurol. 2019 May;266(5):1107-1112. doi: 10.1007/s00415-019-09239-7. Epub 2019 Feb 14.
• [9] Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII 1 Chain. Am J Hum Genet. 2015 Dec 3;97(6):878-85. doi: 10.1016/j.ajhg.2015.10.017. Epub 2015 Nov 25.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [12] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [16] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [17] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [18] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [19] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [20] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [21] Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells. J Nutr. 2006 Jan;136(1):75-82.
• [22] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [23] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [24] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [25] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [26] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [27] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [28] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [29] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [30] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [31] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [32] NCI60 cancer cell line panel data and RNAi analysis help identify EAF2 as a modulator of simvastatin and lovastatin response in HCT-116 cells. PLoS One. 2011 Apr 4;6(4):e18306. doi: 10.1371/journal.pone.0018306.