Details of Drug Off-Target (DOT)

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

• DOT Name: Chondrolectin (CHODL)
• Synonyms: Transmembrane protein MT75
• Gene Name: CHODL
• Related Disease:
  Bulimia nervosa
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Hepatocellular carcinoma
  Spinal muscular atrophy
• UniProt ID: CHODL_HUMAN
• Pfam ID: PF00059
• Sequence:
  MSRVVSLLLGAALLCGHGAFCRRVVSGQKVCFADFKHPCYKMAYFHELSSRVSFQEARLA
  CESEGGVLLSLENEAEQKLIESMLQNLTKPGTGISDGDFWIGLWRNGDGQTSGACPDLYQ
  WSDGSNSQYRNWYTDEPSCGSEKCVVMYHQPTANPGLGGPYLYQWNDDRCNMKHNYICKY
  EPEINPTAPVEKPYLTNQPGDTHQNVVVTEAGIIPNLIYVVIPTIPLLLLILVAFGTCCF
  QMLHKSKGRTKTSPNQSTLWISKSTRKESGMEV
• Function: May play a role in the development of the nervous system such as in neurite outgrowth and elongation. May be involved in motor axon growth and guidance.
• Tissue Specificity: Found in spleen, testis, prostate and fetal liver. Expression limited to vascular muscle of testis, smooth muscle of prostate stroma, heart muscle, skeletal muscle, crypts of small intestine, and red pulp of spleen. B lymphocytes express isoform 2 only; peripheral blood T lymphocytes express isoform 3 only; granulocytes and monocytes express neither isoform 2 nor isoform 3. During development of T lymphocytes, bone marrow progenitor cells express isoform 2 only; thymocytes at different stages of maturation express predominantly isoform 2 and weakly isoform 3, and mature thymocytes express only isoform 2.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bulimia nervosa	DISGQ59Y	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[2]
Spinal muscular atrophy	DISTLKOB	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Chondrolectin (CHODL).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Chondrolectin (CHODL).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Chondrolectin (CHODL).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Chondrolectin (CHODL).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Chondrolectin (CHODL).	[9]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Chondrolectin (CHODL).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Chondrolectin (CHODL).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Chondrolectin (CHODL).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Chondrolectin (CHODL).	[7]

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 affects the methylation of Chondrolectin (CHODL).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Chondrolectin (CHODL).	[12]

References

• [1] Genetic variants associated with disordered eating.Int J Eat Disord. 2013 Sep;46(6):594-608. doi: 10.1002/eat.22133. Epub 2013 Apr 9.
• [2] Expression of CHODL in hepatocellular carcinoma affects invasion and migration of liver cancer cells.Oncol Lett. 2017 Feb;13(2):715-721. doi: 10.3892/ol.2016.5466. Epub 2016 Dec 6.
• [3] Chondrolectin is a novel diagnostic biomarker and a therapeutic target for lung cancer.Clin Cancer Res. 2011 Dec 15;17(24):7712-22. doi: 10.1158/1078-0432.CCR-11-0619. Epub 2011 Oct 20.
• [4] Interaction of Axonal Chondrolectin with Collagen XIXa1 Is Necessary for Precise Neuromuscular Junction Formation.Cell Rep. 2019 Oct 29;29(5):1082-1098.e10. doi: 10.1016/j.celrep.2019.09.033.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [7] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [8] 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.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [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.