Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAN1S5B)

• DOT Name: Calmodulin-binding transcription activator 1 (CAMTA1)
• Gene Name: CAMTA1
• Related Disease:
  Cerebellar dysfunction with variable cognitive and behavioral abnormalities
  Intellectual disability
  Adult glioblastoma
  Amyotrophic lateral sclerosis
  Angiosarcoma
  Astrocytoma
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cerebellar ataxia
  Dedifferentiated liposarcoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Major depressive disorder
  Mood disorder
  Neoplasm
  Neuroblastoma
  Non-insulin dependent diabetes
  Periodontal disease
  Amyotrophic lateral sclerosis type 1
  Colorectal carcinoma
  Coronary heart disease
  Periodontitis
  Prostate carcinoma
• UniProt ID: CMTA1_HUMAN
• PDB ID: 2CXK
• Pfam ID: PF12796 ; PF03859 ; PF00612 ; PF01833
• Sequence:
  MWRAEGKWLPKTSRKSVSQSVFCGTSTYCVLNTVPPIEDDHGNSNSSHVKIFLPKKLLEC
  LPKCSSLPKERHRWNTNEEIAAYLITFEKHEEWLTTSPKTRPQNGSMILYNRKKVKYRKD
  GYCWKKRKDGKTTREDHMKLKVQGVECLYGCYVHSSIIPTFHRRCYWLLQNPDIVLVHYL
  NVPAIEDCGKPCGPILCSINTDKKEWAKWTKEELIGQLKPMFHGIKWTCSNGNSSSGFSV
  EQLVQQILDSHQTKPQPRTHNCLCTGSLGAGGSVHHKCNSAKHRIISPKVEPRTGGYGSH
  SEVQHNDVSEGKHEHSHSKGSSREKRNGKVAKPVLLHQSSTEVSSTNQVEVPDTTQSSPV
  SISSGLNSDPDMVDSPVVTGVSGMAVASVMGSLSQSATVFMSEVTNEAVYTMSPTAGPNH
  HLLSPDASQGLVLAVSSDGHKFAFPTTGSSESLSMLPTNVSEELVLSTTLDGGRKIPETT
  MNFDPDCFLNNPKQGQTYGGGGLKAEMVSSNIRHSPPGERSFSFTTVLTKEIKTEDTSFE
  QQMAKEAYSSSAAAVAASSLTLTAGSSLLPSGGGLSPSTTLEQMDFSAIDSNKDYTSSFS
  QTGHSPHIHQTPSPSFFLQDASKPLPVEQNTHSSLSDSGGTFVMPTVKTEASSQTSSCSG
  HVETRIESTSSLHLMQFQANFQAMTAEGEVTMETSQAAEGSEVLLKSGELQACSSEHYLQ
  PETNGVIRSAGGVPILPGNVVQGLYPVAQPSLGNASNMELSLDHFDISFSNQFSDLINDF
  ISVEGGSSTIYGHQLVSGDSTALSQSEDGARAPFTQAEMCLPCCSPQQGSLQLSSSEGGA
  STMAYMHVAEVVSAASAQGTLGMLQQSGRVFMVTDYSPEWSYPEGGVKVLITGPWQEASN
  NYSCLFDQISVPASLIQPGVLRCYCPAHDTGLVTLQVAFNNQIISNSVVFEYKARALPTL
  PSSQHDWLSLDDNQFRMSILERLEQMERRMAEMTGSQQHKQASGGGSSGGGSGSGNGGSQ
  AQCASGTGALGSCFESRVVVVCEKMMSRACWAKSKHLIHSKTFRGMTLLHLAAAQGYATL
  IQTLIKWRTKHADSIDLELEVDPLNVDHFSCTPLMWACALGHLEAAVVLYKWDRRAISIP
  DSLGRLPLGIARSRGHVKLAECLEHLQRDEQAQLGQNPRIHCPASEEPSTESWMAQWHSE
  AISSPEIPKGVTVIASTNPELRRPRSEPSNYYSSESHKDYPAPKKHKLNPEYFQTRQEKL
  LPTALSLEEPNIRKQSPSSKQSVPETLSPSEGVRDFSRELSPPTPETAAFQASGSQPVGK
  WNSKDLYIGVSTVQVTGNPKGTSVGKEAAPSQVRPREPMSVLMMANREVVNTELGSYRDS
  AENEECGQPMDDIQVNMMTLAEHIIEATPDRIKQENFVPMESSGLERTDPATISSTMSWL
  ASYLADADCLPSAAQIRSAYNEPLTPSSNTSLSPVGSPVSEIAFEKPNLPSAADWSEFLS
  ASTSEKVENEFAQLTLSDHEQRELYEAARLVQTAFRKYKGRPLREQQEVAAAVIQRCYRK
  YKQYALYKKMTQAAILIQSKFRSYYEQKKFQQSRRAAVLIQKYYRSYKKCGKRRQARRTA
  VIVQQKLRSSLLTKKQDQAARKIMRFLRRCRHSPLVDHRLYKRSERIEKGQGT
• Function: Transcriptional activator.
• Tissue Specificity: Normally expressed in non-neoplastic adult central nervous system tissues: detected in whole brain, cerebellum, brain cortex, occipital lobe, frontal lobe, temporal lobe, putamen. Expression levels are low in oligodendroglial tumors, and are reduced by half in oligodendroglioma and astrocytoma cases with 1p loss of heterozygosity. Detected in neuroblastic-type cultured neuroblastoma cells. Expressed in heart and kidney.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar dysfunction with variable cognitive and behavioral abnormalities	DISF3NPW	Definitive	Autosomal dominant	[1]
Intellectual disability	DISMBNXP	Definitive	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[4]
Angiosarcoma	DISIYS9W	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[9]
Dedifferentiated liposarcoma	DISYJUCJ	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[12]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[14]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[8]
Periodontal disease	DISJQHVN	Strong	Genetic Variation	[15]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Limited	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[16]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[17]
Periodontitis	DISI9JOI	Limited	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[18]

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Calmodulin-binding transcription activator 1 (CAMTA1).	[19]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Calmodulin-binding transcription activator 1 (CAMTA1).	[25]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Calmodulin-binding transcription activator 1 (CAMTA1).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Calmodulin-binding transcription activator 1 (CAMTA1).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Calmodulin-binding transcription activator 1 (CAMTA1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[24]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[26]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[31]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Calmodulin-binding transcription activator 1 (CAMTA1).	[32]

References

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• [2] Intragenic CAMTA1 deletions are associated with a spectrum of neurobehavioral phenotypes.Clin Genet. 2015 May;87(5):478-82. doi: 10.1111/cge.12407. Epub 2014 May 20.
• [3] CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem cells.EMBO J. 2011 Aug 19;30(20):4309-22. doi: 10.1038/emboj.2011.301.
• [4] Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis.JAMA Neurol. 2016 Jul 1;73(7):812-20. doi: 10.1001/jamaneurol.2016.1114.
• [5] CAMTA-1 Expression in 24 Cases of Hepatic Epithelioid Hemangioendothelioma in a Single Institute: Diagnostic Utility for Differential Diagnosis from Hepatic Angiosarcoma.In Vivo. 2019 Nov-Dec;33(6):2293-2297. doi: 10.21873/invivo.11736.
• [6] Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene.Clin Cancer Res. 2005 Feb 1;11(3):1119-28.
• [7] Long Noncoding RNA CAMTA1 Promotes Proliferation and Mobility of the Human Breast Cancer Cell Line MDA-MB-231 via Targeting miR-20b.Oncol Res. 2018 May 7;26(4):625-635. doi: 10.3727/096504017X14953948675395. Epub 2017 May 21.
• [8] CAMTA1 T polymorphism is associated with neuropsychological test performance in older adults with cardiovascular disease.Psychogeriatrics. 2011 Sep;11(3):135-40. doi: 10.1111/j.1479-8301.2011.00357.x. Epub 2011 Jun 15.
• [9] Neuropsychological and neuroimaging phenotype induced by a CAMTA1 mutation.Brain Dev. 2014 Sep;36(8):711-5. doi: 10.1016/j.braindev.2013.09.008. Epub 2013 Oct 18.
• [10] Immunohistochemical correlates of recurrent genetic alterations in sarcomas.Genes Chromosomes Cancer. 2019 Feb;58(2):111-123. doi: 10.1002/gcc.22700. Epub 2018 Dec 19.
• [11] Long Noncoding RNA lncCAMTA1 Promotes Proliferation and Cancer Stem Cell-Like Properties of Liver Cancer by Inhibiting CAMTA1.Int J Mol Sci. 2016 Sep 23;17(10):1617. doi: 10.3390/ijms17101617.
• [12] Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways.Nat Commun. 2018 Apr 16;9(1):1470. doi: 10.1038/s41467-018-03819-3.
• [13] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
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• [18] Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy.J Natl Cancer Inst. 2020 Feb 1;112(2):179-190. doi: 10.1093/jnci/djz075.
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• [21] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [22] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [23] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [24] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [25] Epigenome-Wide Assessment of DNA Methylation in the Placenta and Arsenic Exposure in the New Hampshire Birth Cohort Study (USA). Environ Health Perspect. 2016 Aug;124(8):1253-60. doi: 10.1289/ehp.1510437. Epub 2016 Jan 15.
• [26] Evaluation of early biomarkers of muscle anabolic response to testosterone. J Cachexia Sarcopenia Muscle. 2011 Mar;2(1):45-56. doi: 10.1007/s13539-011-0021-y. Epub 2011 Feb 26.
• [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.
• [28] 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.
• [29] 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.
• [30] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [31] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [32] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.