Details of Drug Off-Target (DOT)

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

• DOT Name: Collagen alpha-1(XXII) chain (COL22A1)
• Synonyms: Collagen alpha-1(XXII) chain
• Gene Name: COL22A1
• Related Disease:
  Diffuse systemic sclerosis
  Major depressive disorder
  Muscular dystrophy
  Acute myelogenous leukaemia
  Gastrointestinal stromal tumour
  Chronic hepatitis B virus infection
  Small-cell lung cancer
• UniProt ID: COMA1_HUMAN
• Pfam ID: PF01391 ; PF00092
• Sequence:
  MAGLRGNAVAGLLWMLLLWSGGGGCQAQRAGCKSVHYDLVFLLDTSSSVGKEDFEKVRQW
  VANLVDTFEVGPDRTRVGVVRYSDRPTTAFELGLFGSQEEVKAAARRLAYHGGNTNTGDA
  LRYITARSFSPHAGGRPRDRAYKQVAILLTDGRSQDLVLDAAAAAHRAGIRIFAVGVGEA
  LKEELEEIASEPKSAHVFHVSDFNAIDKIRGKLRRRLCENVLCPSVRVEGDRFKHTNGGT
  KEITGFDLMDLFSVKEILGKRENGAQSSYVRMGSFPVVQSTEDVFPQGLPDEYAFVTTFR
  FRKTSRKEDWYIWQVIDQYSIPQVSIRLDGENKAVEYNAVGAMKDAVRVVFRGSRVNDLF
  DRDWHKMALSIQAQNVSLHIDCALVQTLPIEERENIDIQGKTVIGKRLYDSVPIDFDLQR
  IVIYCDSRHAELETCCDIPSGPCQVTVVTEPPPPPPPQRPPTPGSEQIGFLKTINCSCPA
  GEKGEMGVAGPMGLPGPKGDIGAIGPVGAPGPKGEKGDVGIGPFGQGEKGEKGSLGLPGP
  PGRDGSKGMRGEPGELGEPGLPGEVGMRGPQGPPGLPGPPGRVGAPGLQGERGEKGTRGE
  KGERGLDGFPGKPGDTGQQGRPGPSGVAGPQGEKGDVGPAGPPGVPGSVVQQEGLKGEQG
  APGPRGHQGAPGPPGARGPIGPEGRDGPPGLQGLRGKKGDMGPPGIPGLLGLQGPPGPPG
  VPGPPGPGGSPGLPGEIGFPGKPGPPGPTGPPGKDGPNGPPGPPGTKGEPGERGEDGLPG
  KPGLRGEIGEQGLAGRPGEKGEAGLPGAPGFPGVRGEKGDQGEKGELGLPGLKGDRGEKG
  EAGPAGPPGLPGTTSLFTPHPRMPGEQGPKGEKGDPGLPGEPGLQGRPGELGPQGPTGPP
  GAKGQEGAHGAPGAAGNPGAPGHVGAPGPSGPPGSVGAPGLRGTPGKDGERGEKGAAGEE
  GSPGPVGPRGDPGAPGLPGPPGKGKDGEPGLRGSPGLPGPLGTKAACGKVRGSENCALGG
  QCVKGDRGAPGIPGSPGSRGDPGIGVAGPPGPSGPPGDKGSPGSRGLPGFPGPQGPAGRD
  GAPGNPGERGPPGKPGLSSLLSPGDINLLAKDVCNDCPPGPPGLPGLPGFKGDKGVPGKP
  GREGTEGKKGEAGPPGLPGPPGIAGPQGSQGERGADGEVGQKGDQGHPGVPGFMGPPGNP
  GPPGADGIAGAAGPPGIQGSPGKEGPPGPQGPSGLPGIPGEEGKEGRDGKPGPPGEPGKA
  GEPGLPGPEGARGPPGFKGHTGDSGAPGPRGESGAMGLPGQEGLPGKDGDTGPTGPQGPQ
  GPRGPPGKNGSPGSPGEPGPSGTPGQKGSKGENGSPGLPGFLGPRGPPGEPGEKGVPGKE
  GVPGKPGEPGFKGERGDPGIKGDKGPPGGKGQPGDPGIPGHKGHTGLMGPQGLPGENGPV
  GPPGPPGQPGFPGLRGESPSMETLRRLIQEELGKQLETRLAYLLAQMPPAYMKSSQGRPG
  PPGPPGKDGLPGRAGPMGEPGRPGQGGLEGPSGPIGPKGERGAKGDPGAPGVGLRGEMGP
  PGIPGQPGEPGYAKDGLPGIPGPQGETGPAGHPGLPGPPGPPGQCDPSQCAYFASLAARP
  GNVKGP
• Function: Acts as a cell adhesion ligand for skin epithelial cells and fibroblasts.
• Tissue Specificity: Restrictive expression is observed at tissue junctions such as the myotendinous junction in skeletal and heart muscle, the articular cartilage-synovial fluid junction, or the border between the anagen hair follicle and the dermis in the skin. It is deposited in the basement membrane zone of the myotendinous junction and the hair follicle and associated with the extrafibrillar matrix in cartilage.
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diffuse systemic sclerosis	DISYF5LP	Strong	Biomarker	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[4]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Altered Expression	[5]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Genetic Variation	[6]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[7]

9 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(XXII) chain (COL22A1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[14]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen alpha-1(XXII) chain (COL22A1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Collagen alpha-1(XXII) chain (COL22A1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collagen alpha-1(XXII) chain (COL22A1).	[17]

References

• [1] Brief Report: Whole-Exome Sequencing for Identification of Potential Causal Variants for Diffuse Cutaneous Systemic Sclerosis.Arthritis Rheumatol. 2016 Sep;68(9):2257-62. doi: 10.1002/art.39721.
• [2] A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders.Transl Psychiatry. 2019 May 23;9(1):150. doi: 10.1038/s41398-019-0481-y.
• [3] Knockdown of col22a1 gene in zebrafish induces a muscular dystrophy by disruption of the myotendinous junction.Development. 2013 Nov;140(22):4602-13. doi: 10.1242/dev.096024. Epub 2013 Oct 16.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] Integrated genomic study of quadruple-WT GIST (KIT/PDGFRA/SDH/RAS pathway wild-type GIST).BMC Cancer. 2014 Sep 20;14:685. doi: 10.1186/1471-2407-14-685.
• [6] Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study.Clin Infect Dis. 2019 Nov 13;69(11):1969-1979. doi: 10.1093/cid/ciz084.
• [7] Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.Nat Genet. 2012 Oct;44(10):1111-6. doi: 10.1038/ng.2405. Epub 2012 Sep 2.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] 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.
• [11] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [12] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [16] 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.
• [17] 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.