Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJZ8UEL)

• DOT Name: Neurocalcin-delta (NCALD)
• Gene Name: NCALD
• Related Disease:
  Acute myelogenous leukaemia
  Alzheimer disease
  Cardiovascular disease
  Coeliac disease
  Diabetic kidney disease
  Epithelial ovarian cancer
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Spinal muscular atrophy
  Alcohol dependence
  Alcohol-induced disorders
  Alcohol-related disorders
  Major depressive disorder
• UniProt ID: NCALD_HUMAN
• Pfam ID: PF00036 ; PF13499
• Sequence:
  MGKQNSKLRPEVMQDLLESTDFTEHEIQEWYKGFLRDCPSGHLSMEEFKKIYGNFFPYGD
  ASKFAEHVFRTFDANGDGTIDFREFIIALSVTSRGKLEQKLKWAFSMYDLDGNGYISKAE
  MLEIVQAIYKMVSSVMKMPEDESTPEKRTEKIFRQMDTNRDGKLSLEEFIRGAKSDPSIV
  RLLQCDPSSAGQF
• Function: May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. Binds three calcium ions.
• Tissue Specificity: Retina, cerebrum, cerebellum, brain stem, spinal cord, testis, ovary and small intestine.
• KEGG Pathway: Olfactory transduction (hsa04740)
• Reactome Pathway: Activation of Ca-permeable Kainate Receptor (R-HSA-451308)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Coeliac disease	DISIY60C	Strong	Biomarker	[4]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[1]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[6]
Alcohol dependence	DIS4ZSCO	moderate	Genetic Variation	[7]
Alcohol-induced disorders	DIS3SFYT	moderate	Genetic Variation	[7]
Alcohol-related disorders	DIS3K4KK	moderate	Genetic Variation	[7]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[7]

17 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 Neurocalcin-delta (NCALD).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neurocalcin-delta (NCALD).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neurocalcin-delta (NCALD).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neurocalcin-delta (NCALD).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Neurocalcin-delta (NCALD).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neurocalcin-delta (NCALD).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Neurocalcin-delta (NCALD).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Neurocalcin-delta (NCALD).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Neurocalcin-delta (NCALD).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Neurocalcin-delta (NCALD).	[14]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Neurocalcin-delta (NCALD).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neurocalcin-delta (NCALD).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neurocalcin-delta (NCALD).	[18]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Neurocalcin-delta (NCALD).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Neurocalcin-delta (NCALD).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neurocalcin-delta (NCALD).	[21]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Neurocalcin-delta (NCALD).	[22]

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 decreases the methylation of Neurocalcin-delta (NCALD).	[16]

References

• [1] High NCALD expression predicts poor prognosis of cytogenetic normal acute myeloid leukemia.J Transl Med. 2019 May 20;17(1):166. doi: 10.1186/s12967-019-1904-5.
• [2] Characterization of neurocalcin delta membrane binding by biophysical methods.Colloids Surf B Biointerfaces. 2019 Feb 1;174:291-299. doi: 10.1016/j.colsurfb.2018.11.017. Epub 2018 Nov 12.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] Genes involved in muscle contractility and nutrient signaling pathways within celiac disease risk loci show differential mRNA expression.BMC Med Genet. 2015 Jun 30;16:44. doi: 10.1186/s12881-015-0190-1.
• [5] Polymorphisms in the 3' UTR in the neurocalcin delta gene affect mRNA stability, and confer susceptibility to diabetic nephropathy.Hum Genet. 2007 Nov;122(3-4):397-407. doi: 10.1007/s00439-007-0414-3. Epub 2007 Aug 2.
• [6] Neurocalcin Delta Knockout Impairs Adult Neurogenesis Whereas Half Reduction Is Not Pathological.Front Mol Neurosci. 2019 Feb 12;12:19. doi: 10.3389/fnmol.2019.00019. eCollection 2019.
• [7] Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression.JAMA Psychiatry. 2017 Dec 1;74(12):1234-1241. doi: 10.1001/jamapsychiatry.2017.3275.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 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.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [16] 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.
• [17] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [18] 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.
• [19] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [20] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [21] 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.
• [22] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.