Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3BQUBH)

• DOT Name: Collagen alpha-2(XI) chain (COL11A2)
• Synonyms: Collagen alpha-2(XI) chain
• Gene Name: COL11A2
• Related Disease:
  Autosomal dominant nonsyndromic hearing loss 13
  Autosomal recessive nonsyndromic hearing loss 53
  Classic Hodgkin lymphoma
  Epithelial ovarian cancer
  Nonsyndromic genetic hearing loss
  Otospondylomegaepiphyseal dysplasia
  Otospondylomegaepiphyseal dysplasia, autosomal dominant
  Otospondylomegaepiphyseal dysplasia, autosomal recessive
  Ovarian neoplasm
  Adult glioblastoma
  B-cell neoplasm
  Breast cancer
  Carcinoma
  Castration-resistant prostate carcinoma
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Congenital deformities of limbs
  Connective tissue disorder
  Deafness
  Endometrial carcinoma
  Ewing sarcoma
  Fanconi anemia complementation group A
  Fanconi's anemia
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hereditary breast carcinoma
  Isolated Pierre-Robin syndrome
  Leukemia
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Osteoarthritis
  Pancreatic cancer
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Sensorineural hearing loss disorder
  Small-cell lung cancer
  Stickler syndrome
  Stickler syndrome type 1
  Stickler syndrome type 2
  Acute myelogenous leukaemia
  Triple negative breast cancer
  Autosomal dominant nonsyndromic hearing loss
  Fibrochondrogenesis
  Hearing loss, autosomal recessive
  Breast neoplasm
  Neuroblastoma
  Pancreatic ductal carcinoma
  Rheumatoid arthritis
• UniProt ID: COBA2_HUMAN
• Pfam ID: PF01410 ; PF01391 ; PF02210
• Sequence:
  MERCSRCHRLLLLLPLVLGLSAAPGWAGAPPVDVLRALRFPSLPDGVRRAKGICPADVAY
  RVARPAQLSAPTRQLFPGGFPKDFSLLTVVRTRPGLQAPLLTLYSAQGVRQLGLELGRPV
  RFLYEDQTGRPQPPSQPVFRGLSLADGKWHRVAVAVKGQSVTLIVDCKKRVTRPLPRSAR
  PVLDTHGVIIFGARILDEEVFEGDVQELAIVPGVQAAYESCEQKELECEGGQRERPQNQQ
  PHRAQRSPQQQPSRLHRPQNQEPQSQPTESLYYDYEPPYYDVMTTGTTPDYQDPTPGEEE
  EILESSLLPPLEEEQTDLQVPPTADRFQAEEYGEGGTDPPEGPYDYTYGYGDDYREETEL
  GPALSAETAHSGAAAHGPRGLKGEKGEPAVLEPGMLVEGPPGPEGPAGLIGPPGIQGNPG
  PVGDPGERGPPGRAGLPGSDGAPGPPGTSLMLPFRFGSGGGDKGPVVAAQEAQAQAILQQ
  ARLALRGPPGPMGYTGRPGPLGQPGSPGLKGESGDLGPQGPRGPQGLTGPPGKAGRRGRA
  GADGARGMPGDPGVKGDRGFDGLPGLPGEKGHRGDTGAQGLPGPPGEDGERGDDGEIGPR
  GLPGESGPRGLLGPKGPPGIPGPPGVRGMDGPQGPKGSLGPQGEPGPPGQQGTPGTQGLP
  GPQGAIGPHGEKGPQGKPGLPGMPGSDGPPGHPGKEGPPGTKGNQGPSGPQGPLGYPGPR
  GVKGVDGIRGLKGHKGEKGEDGFPGFKGDIGVKGDRGEVGVPGSRGEDGPEGPKGRTGPT
  GDPGPPGLMGEKGKLGVPGLPGYPGRQGPKGSLGFPGFPGASGEKGARGLSGKSGPRGER
  GPTGPRGQRGPRGATGKSGAKGTSGGDGPHGPPGERGLPGPQGPNGFPGPKGPLGPPGKD
  GLPGHPGQRGEVGFQGKTGPPGPPGVVGPQGAAGETGPMGERGHPGPPGPPGEQGLPGTA
  GKEGTKGDPGPPGAPGKDGPAGLRGFPGERGLPGTAGGPGLKGNEGPSGPPGPAGSPGER
  GAAGSGGPIGPPGRPGPQGPPGAAGEKGVPGEKGPIGPTGRDGVQGPVGLPGPAGPPGVA
  GEDGDKGEVGDPGQKGTKGNKGEHGPPGPPGPIGPVGQPGAAGADGEPGARGPQGHFGAK
  GDEGTRGFNGPPGPIGLQGLPGPSGEKGETGDVGPMGPPGPPGPRGPAGPNGADGPQGPP
  GGVGNLGPPGEKGEPGESGSPGIQGEPGVKGPRGERGEKGESGQPGEPGPPGPKGPTGDD
  GPKGNPGPVGFPGDPGPPGEGGPRGQDGAKGDRGEDGEPGQPGSPGPTGENGPPGPLGKR
  GPAGSPGSEGRQGGKGAKGDPGAIGAPGKTGPVGPAGPAGKPGPDGLRGLPGSVGQQGRP
  GATGQAGPPGPVGPPGLPGLRGDAGAKGEKGHPGLIGLIGPPGEQGEKGDRGLPGPQGSP
  GQKGEMGIPGASGPIGPGGPPGLPGPAGPKGAKGATGPGGPKGEKGVQGPPGHPGPPGEV
  IQPLPIQMPKKTRRSVDGSRLMQEDEAIPTGGAPGSPGGLEEIFGSLDSLREEIEQMRRP
  TGTQDSPARTCQDLKLCHPELPDGEYWVDPNQGCARDAFRVFCNFTAGGETCVTPRDDVT
  QFSYVDSEGSPVGVVQLTFLRLLSVSAHQDVSYPCSGAARDGPLRLRGANEDELSPETSP
  YVKEFRDGCQTQQGRTVLEVRTPVLEQLPVLDASFSDLGAPPRRGGVLLGPVCFMG
• Function: May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  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)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  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

51 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant nonsyndromic hearing loss 13	DISFLETQ	Definitive	Autosomal dominant	[1]
Autosomal recessive nonsyndromic hearing loss 53	DISNONVR	Definitive	Autosomal recessive	[2]
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Genetic Variation	[3]
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[4]
Nonsyndromic genetic hearing loss	DISZX61P	Definitive	Autosomal dominant	[5]
Otospondylomegaepiphyseal dysplasia	DISFFHOF	Definitive	Autosomal dominant	[5]
Otospondylomegaepiphyseal dysplasia, autosomal dominant	DISZ5155	Definitive	Autosomal dominant	[6]
Otospondylomegaepiphyseal dysplasia, autosomal recessive	DISGKOCR	Definitive	Autosomal recessive	[7]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[8]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[9]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[10]
Carcinoma	DISH9F1N	Strong	Biomarker	[11]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[12]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[13]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[14]
Congenital deformities of limbs	DISP4N1Q	Strong	Biomarker	[7]
Connective tissue disorder	DISKXBS3	Strong	Biomarker	[15]
Deafness	DISKCLH4	Strong	Genetic Variation	[16]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[17]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[18]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[19]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[19]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[20]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[21]
Hereditary breast carcinoma	DISAEZT5	Strong	Biomarker	[22]
Isolated Pierre-Robin syndrome	DISVEHG7	Strong	Genetic Variation	[23]
Leukemia	DISNAKFL	Strong	Altered Expression	[24]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[10]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[10]
Osteoarthritis	DIS05URM	Strong	Biomarker	[25]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[26]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[27]
Prostate cancer	DISF190Y	Strong	Biomarker	[28]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[28]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[29]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[30]
Stickler syndrome	DISQWFHN	Strong	Genetic Variation	[31]
Stickler syndrome type 1	DIST5L4S	Strong	Genetic Variation	[31]
Stickler syndrome type 2	DIS4AZNW	Strong	Biomarker	[32]
Acute myelogenous leukaemia	DISCSPTN	moderate	Biomarker	[33]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[34]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[35]
Fibrochondrogenesis	DIS8RUBC	Supportive	Autosomal dominant	[15]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[35]
Breast neoplasm	DISNGJLM	Limited	Genetic Variation	[36]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[37]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Genetic Variation	[38]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Collagen alpha-2(XI) chain (COL11A2) affects the response to substance of Cisplatin.	[50]

8 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-2(XI) chain (COL11A2).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collagen alpha-2(XI) chain (COL11A2).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Collagen alpha-2(XI) chain (COL11A2).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Collagen alpha-2(XI) chain (COL11A2).	[43]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Collagen alpha-2(XI) chain (COL11A2).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Collagen alpha-2(XI) chain (COL11A2).	[46]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Collagen alpha-2(XI) chain (COL11A2).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Collagen alpha-2(XI) chain (COL11A2).	[49]

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-2(XI) chain (COL11A2).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Collagen alpha-2(XI) chain (COL11A2).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Collagen alpha-2(XI) chain (COL11A2).	[48]

References

• [1] Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13). Nat Genet. 1999 Dec;23(4):413-9. doi: 10.1038/70516.
• [2] Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus. J Med Genet. 2005 Oct;42(10):e61. doi: 10.1136/jmg.2005.032615. Epub 2005 Jul 20.
• [3] Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin's lymphoma.Nat Commun. 2013;4:2549. doi: 10.1038/ncomms3549.
• [4] Choosing wisely: Selecting PARP inhibitor combinations to promote anti-tumor immune responses beyond BRCA mutations.Gynecol Oncol. 2020 Feb;156(2):488-497. doi: 10.1016/j.ygyno.2019.09.021. Epub 2019 Oct 17.
• [5] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [6] Stickler syndrome without eye involvement is caused by mutations in COL11A2, the gene encoding the alpha2(XI) chain of type XI collagen. J Pediatr. 1998 Feb;132(2):368-71. doi: 10.1016/s0022-3476(98)70466-4.
• [7] Oto-spondylo-megaepiphyseal dysplasia (OSMED): clinical and radiological findings in sibs homozygous for premature stop codon mutation in the COL11A2 gene. Am J Med Genet A. 2006 Jun 1;140(11):1189-95. doi: 10.1002/ajmg.a.31205.
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• [16] Hearing impairment in Stickler syndrome: a systematic review.Orphanet J Rare Dis. 2012 Oct 30;7:84. doi: 10.1186/1750-1172-7-84.
• [17] Fatostatin suppresses growth and enhances apoptosis by blocking SREBP-regulated metabolic pathways in endometrial carcinoma. Oncol Rep. 2018 Apr;39(4):1919-1929.
• [18] The Ewing Family of Tumors Relies on BCL-2 and BCL-X(L) to Escape PARP Inhibitor Toxicity.Clin Cancer Res. 2019 Mar 1;25(5):1664-1675. doi: 10.1158/1078-0432.CCR-18-0277. Epub 2018 Oct 22.
• [19] Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair.J Natl Cancer Inst. 2016 Feb 4;108(7):djv437. doi: 10.1093/jnci/djv437. Print 2016 Jul.
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• [23] Collagen XI sequence variations in nonsyndromic cleft palate, Robin sequence and micrognathia.Eur J Hum Genet. 2003 Mar;11(3):265-70. doi: 10.1038/sj.ejhg.5200950.
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• [27] Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma.Leukemia. 2020 Jan;34(1):234-244. doi: 10.1038/s41375-019-0542-5. Epub 2019 Aug 19.
• [28] A novel CRISPR-engineered prostate cancer cell line defines the AR-V transcriptome and identifies PARP inhibitor sensitivities.Nucleic Acids Res. 2019 Jun 20;47(11):5634-5647. doi: 10.1093/nar/gkz286.
• [29] Audiological evaluation of affected members from a Dutch DFNA8/12 (TECTA) family.J Assoc Res Otolaryngol. 2007 Mar;8(1):1-7. doi: 10.1007/s10162-006-0060-9. Epub 2006 Nov 30.
• [30] Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer.Cancer Discov. 2019 May;9(5):646-661. doi: 10.1158/2159-8290.CD-18-1020. Epub 2019 Feb 18.
• [31] Non-ocular Stickler syndrome with a novel mutation in COL11A2 diagnosed by massively parallel sequencing in Japanese hearing loss patients.Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:111S-7S. doi: 10.1177/0003489415575044. Epub 2015 Mar 16.
• [32] Targeted disruption of Col11a2 produces a mild cartilage phenotype in transgenic mice: comparison with the human disorder otospondylomegaepiphyseal dysplasia (OSMED).Dev Dyn. 2001 Oct;222(2):141-52. doi: 10.1002/dvdy.1178.
• [33] Targeting ADP-ribosylation by PARP inhibitors in acute myeloid leukaemia and related disorders.Biochem Pharmacol. 2019 Sep;167:133-148. doi: 10.1016/j.bcp.2019.04.019. Epub 2019 Apr 24.
• [34] MUC1-C Integrates Chromatin Remodeling and PARP1 Activity in the DNA Damage Response of Triple-Negative Breast Cancer Cells.Cancer Res. 2019 Apr 15;79(8):2031-2041. doi: 10.1158/0008-5472.CAN-18-3259. Epub 2019 Mar 1.
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