Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH435SV)

DOT Name	Cone-rod homeobox protein (CRX)
Gene Name	CRX
Related Disease	Cone-rod dystrophy 2 ( ) Leber congenital amaurosis 7 ( ) Advanced cancer ( ) Age-related macular degeneration ( ) Amelogenesis imperfecta ( ) Blindness ( ) Cardiac failure ( ) Colitis ( ) Colorectal carcinoma ( ) Congestive heart failure ( ) Crohn disease ( ) Diabetic retinopathy ( ) Fatty acyl-CoA reductase 1 deficiency ( ) Hereditary macular dystrophy ( ) Inflammatory bowel disease ( ) Inherited retinal dystrophy ( ) Leber congenital amaurosis 1 ( ) Long QT syndrome ( ) Myocardial infarction ( ) Neoplasm ( ) Osteoporosis ( ) Pathologic nystagmus ( ) Pineoblastoma ( ) Prostate cancer ( ) Prostate carcinoma ( ) Retinopathy ( ) Septooptic dysplasia ( ) Stargardt disease ( ) Syphilis ( ) Ulcerative colitis ( ) Hepatocellular carcinoma ( ) Retinal degeneration ( ) Cone-rod dystrophy ( ) Leber congenital amaurosis ( ) Retinitis pigmentosa ( ) Autosomal dominant cerebellar ataxia type II ( ) Chronic obstructive pulmonary disease ( ) Combined deficiency of factor V and factor VIII ( ) Disorder of orbital region ( ) Malignant rhabdoid tumour ( ) Proliferative vitreoretinopathy ( )
UniProt ID	CRX_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00046 ; PF03529
Sequence	MMAYMNPGPHYSVNALALSGPSVDLMHQAVPYPSAPRKQRRERTTFTRSQLEELEALFAK TQYPDVYAREEVALKINLPESRVQVWFKNRRAKCRQQRQQQKQQQQPPGGQAKARPAKRK AGTSPRPSTDVCPDPLGISDSYSPPLPGPSGSPTTAVATVSIWSPASESPLPEAQRAGLV ASGPSLTSAPYAMTYAPASAFCSSPSAYGSPSSYFSGLDPYLSPMVPQLGGPALSPLSGP SVGPSLAQSPTSLSGQSYGAYSPVDSLEFKDPTGTWKFTYNPMDPLDYKDQSAWKFQIL
Function	Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors.
Tissue Specificity	Retina.

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cone-rod dystrophy 2	DISX2RWY	Definitive	Autosomal dominant	[1]
Leber congenital amaurosis 7	DISD023K	Definitive	Semidominant	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[3]
Amelogenesis imperfecta	DISGYR9E	Strong	Genetic Variation	[4]
Blindness	DISTIM10	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[8]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[9]
Fatty acyl-CoA reductase 1 deficiency	DISZ4COL	Strong	Genetic Variation	[10]
Hereditary macular dystrophy	DISEYSYY	Strong	Biomarker	[3]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[11]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[12]
Leber congenital amaurosis 1	DISY2B33	Strong	Genetic Variation	[13]
Long QT syndrome	DISMKWS3	Strong	Biomarker	[14]
Myocardial infarction	DIS655KI	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Osteoporosis	DISF2JE0	Strong	Biomarker	[17]
Pathologic nystagmus	DIS1QSPO	Strong	Genetic Variation	[18]
Pineoblastoma	DISQK8F3	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[19]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[19]
Retinopathy	DISB4B0F	Strong	Biomarker	[20]
Septooptic dysplasia	DISXYR1H	Strong	Genetic Variation	[21]
Stargardt disease	DISPXOTO	Strong	Genetic Variation	[22]
Syphilis	DISJ73BS	Strong	Biomarker	[23]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[24]
Retinal degeneration	DISM1JHQ	moderate	Biomarker	[25]
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[26]
Leber congenital amaurosis	DISMGH8F	Supportive	Autosomal dominant	[27]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[28]
Autosomal dominant cerebellar ataxia type II	DIS0PM39	Limited	Altered Expression	[29]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[30]
Combined deficiency of factor V and factor VIII	DISZM9BG	Limited	Biomarker	[31]
Disorder of orbital region	DISH0ECJ	Limited	Genetic Variation	[32]
Malignant rhabdoid tumour	DIS46HZU	Limited	Biomarker	[33]
Proliferative vitreoretinopathy	DISZTEK1	Limited	Biomarker	[34]
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⏷ Show the Full List of 41 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Cone-rod homeobox protein (CRX) decreases the response to substance of Camptothecin.	[38]
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1 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 increases the methylation of Cone-rod homeobox protein (CRX).	[35]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cone-rod homeobox protein (CRX).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cone-rod homeobox protein (CRX).	[37]
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References

1	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2	CRX is a diagnostic marker of retinal and pineal lineage tumors.PLoS One. 2009 Nov 20;4(11):e7932. doi: 10.1371/journal.pone.0007932.
3	Extending the Spectrum of EYS-Associated Retinal Disease to Macular Dystrophy.Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2049-2063. doi: 10.1167/iovs.18-25531.
4	Identification of a locus on chromosome 2q11 at which recessive amelogenesis imperfecta and cone-rod dystrophy cosegregate.Eur J Hum Genet. 2002 Dec;10(12):865-9. doi: 10.1038/sj.ejhg.5200884.
5	A complete, homozygous CRX deletion causing nullizygosity is a new genetic mechanism for Leber congenital amaurosis.Sci Rep. 2018 Mar 22;8(1):5034. doi: 10.1038/s41598-018-22704-z.
6	Cost-of-illness studies in heart failure: a systematic review 2004-2016.BMC Cardiovasc Disord. 2018 May 2;18(1):74. doi: 10.1186/s12872-018-0815-3.
7	Differential responses of neurons in the rat caudal ventrolateral medulla to visceral and somatic noxious stimuli and their alterations in colitis.Brain Res Bull. 2019 Oct;152:299-310. doi: 10.1016/j.brainresbull.2019.07.030. Epub 2019 Aug 1.
8	High Adherence to Surveillance Guidelines in Inflammatory Bowel Disease Patients Results in Low Colorectal Cancer and Dysplasia Rates, While Rates of Dysplasia are Low Before the Suggested Onset of Surveillance.J Crohns Colitis. 2019 Sep 27;13(10):1343-1350. doi: 10.1093/ecco-jcc/jjz066.
9	Cost Effectiveness of Treatments for Diabetic Retinopathy: A Systematic Literature Review.Pharmacoeconomics. 2019 Aug;37(8):995-1010. doi: 10.1007/s40273-019-00800-w.
10	The many faces of peroxisomal disorders: Lessons from a large Arab cohort.Clin Genet. 2019 Feb;95(2):310-319. doi: 10.1111/cge.13481. Epub 2018 Dec 18.
11	A synthetic TLR4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease.J Immunol. 2005 May 15;174(10):6416-23. doi: 10.4049/jimmunol.174.10.6416.
12	The phenotypic variability of retinal dystrophies associated with mutations in CRX, with report of a novel macular dystrophy phenotype.Invest Ophthalmol Vis Sci. 2014 Sep 30;55(10):6934-44. doi: 10.1167/iovs.14-14715.
13	Generation of a human iPSC line, INMi004-A, with a point mutation in CRX associated with autosomal dominant Leber congenital amaurosis.Stem Cell Res. 2019 Jul;38:101476. doi: 10.1016/j.scr.2019.101476. Epub 2019 Jun 3.
14	A Systematic Review on the Cost-Effectiveness of Genetic and Electrocardiogram Testing for Long QT Syndrome in Infants and Young Adults.Value Health. 2015 Jul;18(5):700-8. doi: 10.1016/j.jval.2015.03.1788. Epub 2015 May 16.
15	Systematic assessment of decision-analytic models evaluating diagnostic tests for acute myocardial infarction based on cardiac troponin assays.Expert Rev Pharmacoecon Outcomes Res. 2018 Dec;18(6):619-640. doi: 10.1080/14737167.2018.1512857. Epub 2018 Sep 6.
16	NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma.Cancer Cell. 2018 Mar 12;33(3):435-449.e6. doi: 10.1016/j.ccell.2018.02.006.
17	Efficacy and safety of Zuogui Pill in treating osteoporosis: Study protocol of a systematic review.Medicine (Baltimore). 2019 Feb;98(8):e13936. doi: 10.1097/MD.0000000000013936.
18	Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.Nat Genet. 2000 Jan;24(1):79-83. doi: 10.1038/71732.
19	Peptide T7-modified polypeptide with disulfide bonds for targeted delivery of plasmid DNA for gene therapy of prostate cancer.Int J Nanomedicine. 2018 Oct 30;13:6913-6927. doi: 10.2147/IJN.S180957. eCollection 2018.
20	NMNAT1 variants cause cone and cone-rod dystrophy.Eur J Hum Genet. 2018 Mar;26(3):428-433. doi: 10.1038/s41431-017-0029-7. Epub 2017 Nov 28.
21	Ocular malformations and developmental genes.J AAPOS. 1998 Dec;2(6):317-23. doi: 10.1016/s1091-8531(98)90024-6.
22	Cone rod dystrophies.Orphanet J Rare Dis. 2007 Feb 1;2:7. doi: 10.1186/1750-1172-2-7.
23	Rapid diagnostic test for antenatal syphilis screening in low-income and middle-income countries: a systematic review and meta-analysis.BMJ Open. 2018 Feb 21;8(2):e018132. doi: 10.1136/bmjopen-2017-018132.
24	Gadoxetic acid-enhanced MRI for the characterization of hepatocellular carcinoma: A systematic review and meta-analysis.J Magn Reson Imaging. 2017 Jan;45(1):281-290. doi: 10.1002/jmri.25345. Epub 2016 Jun 14.
25	A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene.Am J Hum Genet. 1998 Nov;63(5):1307-15. doi: 10.1086/302101.
26	A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree. Int J Ophthalmol. 2015 Dec 18;8(6):1112-7. doi: 10.3980/j.issn.2222-3959.2015.06.06. eCollection 2015.
27	Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function. Hum Mol Genet. 1999 Feb;8(2):299-305. doi: 10.1093/hmg/8.2.299.
28	Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
29	Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7.Neuron. 2001 Sep 27;31(6):913-27. doi: 10.1016/s0896-6273(01)00422-6.
30	The Qigong Wuqinxi for chronic obstructive pulmonary disease: Protocol for a systematic review and meta-analysis.Medicine (Baltimore). 2019 Jul;98(30):e16633. doi: 10.1097/MD.0000000000016633.
31	Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII.FEBS Lett. 2010 Mar 5;584(5):878-82. doi: 10.1016/j.febslet.2010.02.009. Epub 2010 Feb 9.
32	Pathogenicity discrimination and genetic test reference for CRX variants based on genotype-phenotype analysis.Exp Eye Res. 2019 Dec;189:107846. doi: 10.1016/j.exer.2019.107846. Epub 2019 Oct 15.
33	CRX/OTX3: a useful marker in the differential diagnosis of tumors of the pineal region and indicator of photoreceptor differentiation in medulloblastomas and atypical teratoid rhabdoid tumors.Appl Immunohistochem Mol Morphol. 2013 May;21(3):248-53. doi: 10.1097/PAI.0b013e3182649dad.
34	Expression of VEGF-A, Otx homeobox and p53 family genes in proliferative vitreoretinopathy.Mediators Inflamm. 2013;2013:857380. doi: 10.1155/2013/857380. Epub 2013 Oct 21.
35	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.
36	Development of human retinal organoid models for bisphenol toxicity assessment. Ecotoxicol Environ Saf. 2022 Oct 15;245:114094. doi: 10.1016/j.ecoenv.2022.114094. Epub 2022 Sep 18.
37	Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
38	ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.