Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN2XE4T)

• DOT Name: Calcium-binding protein 8 (CALN1)
• Synonyms: CaBP8; Calneuron I; Calneuron-1
• Gene Name: CALN1
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Epileptic encephalopathy
  Gastric cancer
  Neoplasm
  Schizophrenia
  Stomach cancer
  X-linked Opitz G/BBB syndrome
• UniProt ID: CABP8_HUMAN
• Pfam ID: PF13499
• Sequence:
  MRLPEQPGEGKPENEKKGDGGALGGGEEPPRSQAPDFPTWEKMPFHHVTAGLLYKGNYLN
  RSLSAGSDSEQLANISVEELDEIREAFRVLDRDGNGFISKQELGMAMRSLGYMPSEVELA
  IIMQRLDMDGDGQVDFDEFMTILGPKLVSSEGRDGFLGNTIDSIFWQFDMQRITLEELKH
  ILYHAFRDHLTMKDIENIIINEEESLNETSGNCQTEFEGVHSQKQNRQTCVRKSLICAFA
  MAFIISVMLIAANQILRSGME
• Function: Negatively regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity. May play a role in the physiology of neurons and is potentially important in memory and learning.
• Tissue Specificity: Brain specific.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]
Epileptic encephalopathy	DISZOCA3	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[3]
X-linked Opitz G/BBB syndrome	DISQ14EC	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Calcium-binding protein 8 (CALN1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Calcium-binding protein 8 (CALN1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calcium-binding protein 8 (CALN1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Calcium-binding protein 8 (CALN1).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Calcium-binding protein 8 (CALN1).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Calcium-binding protein 8 (CALN1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Calcium-binding protein 8 (CALN1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Calcium-binding protein 8 (CALN1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Calcium-binding protein 8 (CALN1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Calcium-binding protein 8 (CALN1).	[6]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Calcium-binding protein 8 (CALN1).	[10]

References

• [1] Characterization of DNA hydroxymethylation profile in cervical cancer.Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2706-2714. doi: 10.1080/21691401.2019.1634578.
• [2] Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1.Biochem Biophys Res Commun. 2018 Jun 2;500(2):170-176. doi: 10.1016/j.bbrc.2018.04.016. Epub 2018 Apr 11.
• [3] Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer.Oncotarget. 2014 Apr 30;5(8):2318-29. doi: 10.18632/oncotarget.1913.
• [4] Prediction of causal genes and gene expression analysis of attention-deficit hyperactivity disorder in the different brain region, a comprehensive integrative analysis of ADHD.Behav Brain Res. 2019 May 17;364:183-192. doi: 10.1016/j.bbr.2019.02.010. Epub 2019 Feb 6.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] 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.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] 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.
• [13] 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.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.