Details of Drug Off-Target (DOT)

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

• DOT Name: Gamma-crystallin C (CRYGC)
• Synonyms: Gamma-C-crystallin; Gamma-crystallin 2-1; Gamma-crystallin 3
• Gene Name: CRYGC
• Related Disease:
  Cataract 2, multiple types
  Cataract 9 multiple types
  Multiple sclerosis
  Systemic lupus erythematosus
  Acute otitis media
  Advanced cancer
  Aortic valve stenosis
  Atrial fibrillation
  Cardiac failure
  Cataract 20 multiple types
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Immunodeficiency
  Otitis media
  Renal fibrosis
  Retinal degeneration
  Tuberculosis
  Chronic obstructive pulmonary disease
  Neuroblastoma
  Small lymphocytic lymphoma
  Cataract - microcornea syndrome
  Early-onset lamellar cataract
  Early-onset nuclear cataract
  Pulverulent cataract
  Asthma
  Cataract
  Colorectal carcinoma
  Neoplasm
• UniProt ID: CRGC_HUMAN
• PDB ID: 2NBR
• Pfam ID: PF00030
• Sequence:
  MGKITFYEDRAFQGRSYETTTDCPNLQPYFSRCNSIRVESGCWMLYERPNYQGQQYLLRR
  GEYPDYQQWMGLSDSIRSCCLIPQTVSHRLRLYEREDHKGLMMELSEDCPSIQDRFHLSE
  IRSLHVLEGCWVLYELPNYRGRQYLLRPQEYRRCQDWGAMDAKAGSLRRVVDLY
• Function: Crystallins are the dominant structural components of the vertebrate eye lens.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract 2, multiple types	DISF9EJ8	Definitive	Autosomal dominant	[1]
Cataract 9 multiple types	DIS9JQ8P	Definitive	Autosomal dominant	[1]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	Definitive	Biomarker	[2]
Acute otitis media	DISL8D8G	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Aortic valve stenosis	DISW7AQ9	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Cataract 20 multiple types	DISN0IHS	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Immunodeficiency	DIS093I0	Strong	Biomarker	[9]
Otitis media	DISGZDUO	Strong	Altered Expression	[3]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[10]
Retinal degeneration	DISM1JHQ	Strong	Biomarker	[11]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[12]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[13]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[14]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[15]
Cataract - microcornea syndrome	DISL51AQ	Supportive	Autosomal dominant	[16]
Early-onset lamellar cataract	DISR7WXX	Supportive	Autosomal dominant	[17]
Early-onset nuclear cataract	DISGIHUY	Supportive	Autosomal dominant	[18]
Pulverulent cataract	DISMJ2AH	Supportive	Autosomal dominant	[19]
Asthma	DISW9QNS	Limited	Altered Expression	[20]
Cataract	DISUD7SL	Limited	Genetic Variation	[21]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[22]
Neoplasm	DISZKGEW	Limited	Biomarker	[23]

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 Gamma-crystallin C (CRYGC).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Gamma-crystallin C (CRYGC).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Gamma-crystallin C (CRYGC).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Gamma-crystallin C (CRYGC).	[25]

References

• [1] The gamma-crystallins and human cataracts: a puzzle made clearer. Am J Hum Genet. 1999 Nov;65(5):1261-7. doi: 10.1086/302619.
• [2] CCL genes in multiple sclerosis and systemic lupus erythematosus.J Neuroimmunol. 2008 Aug 30;200(1-2):145-52. doi: 10.1016/j.jneuroim.2008.05.016. Epub 2008 Jul 3.
• [3] Otitis Media and Nasopharyngeal Colonization in ccl3(-/-) Mice.Infect Immun. 2017 Oct 18;85(11):e00148-17. doi: 10.1128/IAI.00148-17. Print 2017 Nov.
• [4] Likert vs PI-RADS v2: a comparison of two radiological scoring systems for detection of clinically significant prostate cancer.BJU Int. 2020 Jan;125(1):49-55. doi: 10.1111/bju.14916. Epub 2019 Nov 1.
• [5] MicroRNA-19b is a potential biomarker of increased myocardial collagen cross-linking in patients with aortic stenosis and heart failure.Sci Rep. 2017 Jan 16;7:40696. doi: 10.1038/srep40696.
• [6] Combination of Circulating Type I Collagen-Related Biomarkers Is AssociatedWith AtrialFibrillation.J Am Coll Cardiol. 2019 Apr 2;73(12):1398-1410. doi: 10.1016/j.jacc.2018.12.074.
• [7] A 6-bp deletion in the Crygc gene leading to a nuclear and radial cataract in the mouse.Invest Ophthalmol Vis Sci. 2002 Jan;43(1):236-40.
• [8] Investigation of apoptotic effect of juglone on CCL-228-SW 480 colon cancer cell line.J Cancer Res Ther. 2019 Jan-Mar;15(1):68-74. doi: 10.4103/jcrt.JCRT_880_17.
• [9] In Human Immunodeficiency Virus primary infection, early combined antiretroviral therapy reduced T-cell activation but failed to restore their polyfunctionality.Immunology. 2019 Aug;157(4):322-330. doi: 10.1111/imm.13089. Epub 2019 Jul 8.
• [10] Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7-CTLA-4 and CCL-CCR pathways.Mol Cell Biochem. 2018 Apr;441(1-2):191-199. doi: 10.1007/s11010-017-3185-8. Epub 2017 Sep 5.
• [11] Genetic, age and light mediated effects on crystallin protein expression in the retina.Photochem Photobiol. 2006 Jul-Aug;82(4):1088-96. doi: 10.1562/2005-06-30-RA-599.
• [12] Dual-protected amino acid derivatives as new antitubercular agents.Chem Biol Drug Des. 2018 Aug;92(2):1576-1580. doi: 10.1111/cbdd.13315. Epub 2018 May 31.
• [13] Chemokine expression by small sputum macrophages in COPD.Mol Med. 2011;17(7-8):762-70. doi: 10.2119/molmed.2010.00202. Epub 2011 Feb 9.
• [14] Targeted liposomal c-myc antisense oligodeoxynucleotides induce apoptosis and inhibit tumor growth and metastases in human melanoma models.Clin Cancer Res. 2003 Oct 1;9(12):4595-605.
• [15] Immunotoxins in cancer therapy: Review and update.Int Rev Immunol. 2017 Jul 4;36(4):207-219. doi: 10.1080/08830185.2017.1284211. Epub 2017 Mar 1.
• [16] A nonsense mutation of CRYGC associated with autosomal dominant congenital nuclear cataracts and microcornea in a Chinese pedigree. Mol Vis. 2012;18:1874-80. Epub 2012 Jul 11.
• [17] Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts. J Med Genet. 2002 May;39(5):352-8. doi: 10.1136/jmg.39.5.352.
• [18] A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family. Mol Vis. 2008 Jul 9;14:1272-6.
• [19] A 5-base insertion in the gammaC-crystallin gene is associated with autosomal dominant variable zonular pulverulent cataract. Hum Genet. 2000 May;106(5):531-7. doi: 10.1007/s004390000289.
• [20] A CCL chemokine-derived peptide (CDIP-2) exerts anti-inflammatory activity via CCR1, CCR2 and CCR3 chemokine receptors: Implications as a potential therapeutic treatment of asthma.Int Immunopharmacol. 2014 May;20(1):1-11. doi: 10.1016/j.intimp.2014.01.032. Epub 2014 Feb 20.
• [21] A novel mutation impairing the tertiary structure and stability of C-crystallin (CRYGC) leads to cataract formation in humans and zebrafish lens.Hum Mutat. 2012 Feb;33(2):391-401. doi: 10.1002/humu.21648. Epub 2011 Dec 8.
• [22] In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human Stathmin 1 oncoprotein.DNA Cell Biol. 2011 Sep;30(9):715-26. doi: 10.1089/dna.2011.1240. Epub 2011 May 25.
• [23] Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members.Int J Oncol. 2011 Aug;39(2):483-91. doi: 10.3892/ijo.2011.1054. Epub 2011 May 25.
• [24] 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.
• [25] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [26] 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.
• [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.