Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYQ28V9)

• DOT Name: IQ calmodulin-binding motif-containing protein 1 (IQCB1)
• Synonyms: Nephrocystin-5; p53 and DNA damage-regulated IQ motif protein; PIQ
• Gene Name: IQCB1
• Related Disease:
  Leber congenital amaurosis 9
  Senior-Loken syndrome 5
  Autism spectrum disorder
  Bardet biedl syndrome
  Beta-thalassemia major
  Blindness
  Inherited retinal dystrophy
  Jalili syndrome
  Kidney failure
  Klinefelter syndrome
  Multiple sclerosis
  Nephronophthisis
  Nephronophthisis 3
  Retinitis pigmentosa
  Schizophrenia
  Sjogren-Larsson syndrome
  Cystic kidney disease
  Nephropathy
  Retinopathy
  Leber congenital amaurosis
  Senior-Loken syndrome
  Ciliopathy
  Digestive system neoplasm
  Stroke
• UniProt ID: IQCB1_HUMAN
• Pfam ID: PF00612
• Sequence:
  MKPTGTDPRILSIAAEVAKSPEQNVPVILLKLKEIINITPLGSSELKKIKQDIYCYDLIQ
  YCLLVLSQDYSRIQGGWTTISQLTQILSHCCVGLEPGEDAEEFYNELLPSAAENFLVLGR
  QLQTCFINAAKAEEKDELLHFFQIVTDSLFWLLGGHVELIQNVLQSDHFLHLLQADNVQI
  GSAVMMMLQNILQINSGDLLRIGRKALYSILDEVIFKLFSTPSPVIRSTATKLLLLMAES
  HQEILILLRQSTCYKGLRRLLSKQETGTEFSQELRQLVGLLSPMVYQEVEEQKLHQAACL
  IQAYWKGFQTRKRLKKLPSAVIALQRSFRSKRSKMLLEINRQKEEEDLKLQLQLQRQRAM
  RLSRELQLSMLEIVHPGQVEKHYREMEEKSALIIQKHWRGYRERKNFHQQRQSLIEYKAA
  VTLQRAALKFLAKCRKKKKLFAPWRGLQELTDARRVELKKRVDDYVRRHLGSPMSDVVSR
  ELHAQAQERLQHYFMGRALEERAQQHREALIAQISTNVEQLMKAPSLKEAEGKEPELFLS
  RSRPVAAKAKQAHLTTLKHIQAPWWKKLGEESGDEIDVPKDELSIELENLFIGGTKPP
• Function: Involved in ciliogenesis. The function in an early step in cilia formation depends on its association with CEP290/NPHP6. Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2 and BBS5 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating CEP290/NPHP6.
• Tissue Specificity: Ubiquitously expressed in fetal and adult tissues. Localized to the outer segments and connecting cilia of photoreceptor cells. Up-regulated in a number of primary colorectal and gastric tumors.
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leber congenital amaurosis 9	DIS35YGW	Definitive	Autosomal recessive	[1]
Senior-Loken syndrome 5	DISAQTI0	Definitive	Autosomal recessive	[2]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[3]
Bardet biedl syndrome	DISTBNZW	Strong	Biomarker	[4]
Beta-thalassemia major	DISW06BV	Strong	Biomarker	[5]
Blindness	DISTIM10	Strong	Biomarker	[6]
Inherited retinal dystrophy	DISGGL77	Strong	Biomarker	[7]
Jalili syndrome	DIS3FJ55	Strong	Biomarker	[7]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[8]
Klinefelter syndrome	DISOUI7W	Strong	Biomarker	[9]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[10]
Nephronophthisis	DISXU4HY	Strong	Genetic Variation	[11]
Nephronophthisis 3	DIS4CC6R	Strong	Genetic Variation	[12]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[13]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[14]
Sjogren-Larsson syndrome	DISP943Y	Strong	Genetic Variation	[11]
Cystic kidney disease	DISRT1LM	moderate	Biomarker	[15]
Nephropathy	DISXWP4P	moderate	Genetic Variation	[16]
Retinopathy	DISB4B0F	moderate	Biomarker	[15]
Leber congenital amaurosis	DISMGH8F	Supportive	Autosomal dominant	[8]
Senior-Loken syndrome	DISGBSGP	Supportive	Autosomal recessive	[17]
Ciliopathy	DIS10G4I	Limited	Genetic Variation	[11]
Digestive system neoplasm	DISPOJCT	Limited	Biomarker	[18]
Stroke	DISX6UHX	Limited	Biomarker	[19]

12 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 IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[23]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[24]
Selenium	DM25CGV	Approved	Selenium decreases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[25]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[26]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[27]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of IQ calmodulin-binding motif-containing protein 1 (IQCB1).	[31]

References

• [1] Comprehensive mutation analysis by whole-exome sequencing in 41 Chinese families with Leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2013 Jun 26;54(6):4351-7. doi: 10.1167/iovs.13-11606.
• [2] 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.
• [3] IQ discrepancy differentiates levels of fine motor skills and their relationship in children with autism spectrum disorders.Neuropsychiatr Dis Treat. 2018 Feb 20;14:597-605. doi: 10.2147/NDT.S153102. eCollection 2018.
• [4] Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integrity, ciliary trafficking and cargo delivery.Hum Mol Genet. 2015 Apr 15;24(8):2185-200. doi: 10.1093/hmg/ddu738. Epub 2014 Dec 30.
• [5] Neurocognitive dysfunction in children with thalassemia major: psychometric, neurophysiologic and radiologic evaluation.Hematology. 2017 Dec;22(10):617-622. doi: 10.1080/10245332.2017.1338212. Epub 2017 Jun 16.
• [6] Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes).Sci Rep. 2017 Mar 21;7:43918. doi: 10.1038/srep43918.
• [7] Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1.Mol Genet Genomics. 2018 Jun;293(3):699-710. doi: 10.1007/s00438-018-1417-6. Epub 2018 Jan 10.
• [8] IQCB1 mutations in patients with leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2011 Feb 11;52(2):834-9. doi: 10.1167/iovs.10-5221.
• [9] Neuropsychological profiles of adults with Klinefelter syndrome.J Int Neuropsychol Soc. 2001 May;7(4):446-56. doi: 10.1017/s1355617701744013.
• [10] Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors.Mult Scler. 2016 Dec;22(14):1783-1793. doi: 10.1177/1352458516635873. Epub 2016 Feb 26.
• [11] Rescue of cone function in cone-only Nphp5 knockout mouse model with Leber congenital amaurosis phenotype.Mol Vis. 2018 Dec 30;24:834-846. eCollection 2018.
• [12] Identification of a gene for renal-hepatic-pancreatic dysplasia by microarray-based homozygosity mapping. J Mol Diagn. 2010 Jan;12(1):125-31. doi: 10.2353/jmoldx.2010.090033. Epub 2009 Dec 10.
• [13] Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
• [14] Polish Adult Reading Test (PART) - construction of Polish test for estimating the level of premorbid intelligence in schizophrenia.Psychiatr Pol. 2017 Aug 29;51(4):673-685. doi: 10.12740/PP/OnlineFirst/63207. Epub 2017 Aug 29.
• [15] Specific retinal phenotype in early IQCB1-related disease.Eye (Lond). 2018 Mar;32(3):646-651. doi: 10.1038/eye.2017.283. Epub 2017 Dec 8.
• [16] Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused by NPHP5 mutation.Hum Mol Genet. 2016 Oct 1;25(19):4211-4226. doi: 10.1093/hmg/ddw254. Epub 2016 Aug 9.
• [17] Senior-L?ken syndrome: a syndromic form of retinal dystrophy associated with nephronophthisis. Vision Res. 2012 Dec 15;75:88-97. doi: 10.1016/j.visres.2012.07.003. Epub 2012 Jul 20.
• [18] Cloning and characterization of a p53 and DNA damage down-regulated gene PIQ that codes for a novel calmodulin-binding IQ motif protein and is up-regulated in gastrointestinal cancers.Cancer Res. 2005 Dec 1;65(23):10725-33. doi: 10.1158/0008-5472.CAN-05-1132.
• [19] Language and cognitive outcomes after childhood stroke: Theoretical implications for hemispheric specialization.Cortex. 2019 Nov;120:509-523. doi: 10.1016/j.cortex.2019.07.020. Epub 2019 Aug 17.
• [20] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [21] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [22] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [23] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [24] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [25] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [26] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [27] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [28] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [29] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [30] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [31] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.