Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWE0T6Q)

• DOT Name: Calcium-responsive transcription factor (CARF)
• Synonyms: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 8 protein; Calcium-response factor; CaRF; Testis development protein NYD-SP24
• Gene Name: CARF
• Related Disease:
  Anorexia nervosa cachexia
  Bipolar disorder
  Colorectal carcinoma
  Glioblastoma multiforme
  Intellectual disability
  Major depressive disorder
  Obesity
  Schizophrenia
  Coronary heart disease
  Neoplasm
  Advanced cancer
  Migraine disorder
• UniProt ID: CARTF_HUMAN
• Pfam ID: PF15299
• Sequence:
  MEQSNDSLRVNHNDGEESKTSAQVFEHLICMDSRDSSFGQNDSPTVLPITTREANNSLIS
  QNIPGPLTQTQTLSAEQFHLVDQNGQAIQYELQSLGESNAQMMIVASPTENGQVLRVIPP
  TQTGMAQVIIPQGQLVDVNSPRDVPEEKPSNRNLPTVRVDTLADNTSNYILHPQTSFPLP
  KKSVTGMLEEPLLGPLQPLSSNTPIWACRLRSCEKIGDSYRGYCVSETELESVLTFHKQQ
  TQSVWGTRQSPSPAKPATRLMWKSQYVPYDGIPFVNAGSRAVVMECQYGPRRKGFQLKKV
  SEQESRSCQLYKATCPARIYIKKVQKFPEYRVPTDPKIDKKIIRMEQEKAFNMLKKNLVD
  AGGVLRWYVQLPTQQAHQYHELETPCLTLSPSPFPVSSLEEEETAVRDENCALPSRLHPQ
  VAHKIQELVSQGIEQVYAVRKQLRKFVERELFKPDEVPERHNLSFFPTVNDIKNHIHEVQ
  KSLRNGDTVYNSEIIPATLQWTTDSGNILKETMTVTFAEGNSPGESITTKVETNQTRGSL
  SPEPTHLLSSLSSFQPKIFTQLQGLQLQPRYTSPDESPAVVSVNNQPSSSPSGLLDTIGS
  AVMNNNSLLLGQSHSLQRDTCLTQNNSTASTMGNLPEPDQNLVAMDELVEVGDVEDTGNL
  EGTVHRILLGDVQTIPIQIIDNHSALIEENPESTISVSQVKQEPKEPALSMEAKKTVDYK
  KLSAT
• Function: Acts as a transcriptional activator that mediates the calcium- and neuron-selective induction of BDNF exon III transcription. Binds to the consensus calcium-response element CaRE1 5'-CTATTTCGAG-3' sequence.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[5]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[6]
Neoplasm	DISZKGEW	Disputed	Genetic Variation	[7]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[8]
Migraine disorder	DISFCQTG	Limited	Genetic Variation	[9]

8 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 Calcium-responsive transcription factor (CARF).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Calcium-responsive transcription factor (CARF).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Calcium-responsive transcription factor (CARF).	[12]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Calcium-responsive transcription factor (CARF).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Calcium-responsive transcription factor (CARF).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Calcium-responsive transcription factor (CARF).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calcium-responsive transcription factor (CARF).	[17]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Calcium-responsive transcription factor (CARF).	[18]

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 affects the methylation of Calcium-responsive transcription factor (CARF).	[14]

References

• [1] Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index.Mol Psychiatry. 2017 Feb;22(2):192-201. doi: 10.1038/mp.2016.71. Epub 2016 May 17.
• [2] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [3] CARF, As An Oncogene, Promotes Colorectal Cancer Stemness By Activating ERBB Signaling Pathway.Onco Targets Ther. 2019 Nov 1;12:9041-9051. doi: 10.2147/OTT.S225733. eCollection 2019.
• [4] NFAT1-Mediated Regulation of NDEL1 Promotes Growth and Invasion of Glioma Stem-like Cells.Cancer Res. 2019 May 15;79(10):2593-2603. doi: 10.1158/0008-5472.CAN-18-3297. Epub 2019 Apr 2.
• [5] Intragenic CAMTA1 rearrangements cause non-progressive congenital ataxia with or without intellectual disability. J Med Genet. 2012 Jun;49(6):400-8. doi: 10.1136/jmedgenet-2012-100856.
• [6] Association analyses based on false discovery rate implicate new loci for coronary artery disease.Nat Genet. 2017 Sep;49(9):1385-1391. doi: 10.1038/ng.3913. Epub 2017 Jul 17.
• [7] Mutational and LOH analyses of the chromosome 4q region in esophageal adenocarcinoma.Oncology. 2006;70(3):168-72. doi: 10.1159/000094444. Epub 2006 Jul 7.
• [8] Molecular Insights Into Withaferin-A-Induced Senescence: Bioinformatics and Experimental Evidence to the Role of NFB and CARF.J Gerontol A Biol Sci Med Sci. 2019 Jan 16;74(2):183-191. doi: 10.1093/gerona/gly107.
• [9] Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [14] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] 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.
• [18] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.