Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7GS82E)

• DOT Name: Collagen alpha-1(XXI) chain (COL21A1)
• Synonyms: Collagen alpha-1(XXI) chain
• Gene Name: COL21A1
• Related Disease:
  Cleft lip
  Cocaine addiction
  Isolated cleft lip
  Psychotic disorder
  High blood pressure
• UniProt ID: COLA1_HUMAN
• Pfam ID: PF01391 ; PF00092
• Sequence:
  MAHYITFLCMVLVLLLQNSVLAEDGEVRSSCRTAPTDLVFILDGSYSVGPENFEIVKKWL
  VNITKNFDIGPKFIQVGVVQYSDYPVLEIPLGSYDSGEHLTAAVESILYLGGNTKTGKAI
  QFALDYLFAKSSRFLTKIAVVLTDGKSQDDVKDAAQAARDSKITLFAIGVGSETEDAELR
  AIANKPSSTYVFYVEDYIAISKIREVMKQKLCEESVCPTRIPVAARDERGFDILLGLDVN
  KKVKKRIQLSPKKIKGYEVTSKVDLSELTSNVFPEGLPPSYVFVSTQRFKVKKIWDLWRI
  LTIDGRPQIAVTLNGVDKILLFTTTSVINGSQVVTFANPQVKTLFDEGWHQIRLLVTEQD
  VTLYIDDQQIENKPLHPVLGILINGQTQIGKYSGKEETVQFDVQKLRIYCDPEQNNRETA
  CEIPGFNGECLNGPSDVGSTPAPCICPPGKPGLQGPKGDPGLPGNPGYPGQPGQDGKPGY
  QGIAGTPGVPGSPGIQGARGLPGYKGEPGRDGDKGDRGLPGFPGLHGMPGSKGEMGAKGD
  KGSPGFYGKKGAKGEKGNAGFPGLPGPAGEPGRHGKDGLMGSPGFKGEAGSPGAPGQDGT
  RGEPGIPGFPGNRGLMGQKGEIGPPGQQGKKGAPGMPGLMGSNGSPGQPGTPGSKGSKGE
  PGIQGMPGASGLKGEPGATGSPGEPGYMGLPGIQGKKGDKGNQGEKGIQGQKGENGRQGI
  PGQQGIQGHHGAKGERGEKGEPGVRGAIGSKGESGVDGLMGPAGPKGQPGDPGPQGPPGL
  DGKPGREFSEQFIRQVCTDVIRAQLPVLLQSGRIRNCDHCLSQHGSPGIPGPPGPIGPEG
  PRGLPGLPGRDGVPGLVGVPGRPGVRGLKGLPGRNGEKGSQGFGYPGEQGPPGPPGPEGP
  PGISKEGPPGDPGLPGKDGDHGKPGIQGQPGPPGICDPSLCFSVIARRDPFRKGPNY
• Tissue Specificity: Highly expressed in lymph node, jejunum, pancreas, stomach, trachea, testis, uterus and placenta; moderately expressed in brain, colon, lung, prostate, spinal cord, salivary gland and vascular smooth-muscle cells and very weakly expressed in heart, liver, kidney, bone marrow, spleen, thymus, skeletal muscle, adrenal gland and peripheral leukocytes. Expression in heart was higher in the right ventricle and atrium than in the left ventricle and atrium.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Collagen chain trimerization (R-HSA-8948216)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cleft lip	DISV3XW6	Strong	Genetic Variation	[1]
Cocaine addiction	DISHTRXG	Strong	Biomarker	[2]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[1]
Psychotic disorder	DIS4UQOT	Strong	Genetic Variation	[3]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Collagen alpha-1(XXI) chain (COL21A1) affects the response to substance of Cocaine.	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Collagen alpha-1(XXI) chain (COL21A1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[9]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[14]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Collagen alpha-1(XXI) chain (COL21A1).	[15]

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(XXI) chain (COL21A1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-1(XXI) chain (COL21A1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Collagen alpha-1(XXI) chain (COL21A1).	[12]

References

• [1] Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate.Mol Genet Genomic Med. 2019 May;7(5):e635. doi: 10.1002/mgg3.635. Epub 2019 Mar 28.
• [2] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [3] Genome-wide association study of atypical psychosis.Am J Med Genet B Neuropsychiatr Genet. 2013 Oct;162B(7):679-86. doi: 10.1002/ajmg.b.32164.
• [4] Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.Nat Genet. 2016 Oct;48(10):1151-1161. doi: 10.1038/ng.3654. Epub 2016 Sep 12.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] 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.
• [13] 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.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [16] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.