Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY9A84V)

• DOT Name: Protein cornichon homolog 1 (CNIH1)
• Synonyms: CNIH-1; Cornichon family AMPA receptor auxiliary protein 1; Protein cornichon homolog; T-cell growth-associated molecule 77; TGAM77
• Gene Name: CNIH1
• UniProt ID: CNIH1_HUMAN
• Pfam ID: PF03311
• Sequence:
  MAFTFAAFCYMLALLLTAALIFFAIWHIIAFDELKTDYKNPIDQCNTLNPLVLPEYLIHA
  FFCVMFLCAAEWLTLGLNMPLLAYHIWRYMSRPVMSGPGLYDPTTIMNADILAYCQKEGW
  CKLAFYLLAFFYYLYGMIYVLVSS
• Function: Involved in the selective transport and maturation of TGF-alpha family proteins.
• Tissue Specificity: Highly expressed in heart, liver, skeletal muscle, pancreas, adrenal medulla and cortex, thyroid, testis, spleen, appendix, peripheral blood lymphocytes and bone marrow. Lower expression found in brain, placenta, lung, kidney, ovary, small intestine, stomach, lymph node, thymus and fetal liver. Expression is up-regulated in dorsolateral prefrontal cortex of patients with schizophrenia (postmortem brain study).
• Reactome Pathway:
  Cargo concentration in the ER (R-HSA-5694530)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein cornichon homolog 1 (CNIH1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein cornichon homolog 1 (CNIH1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein cornichon homolog 1 (CNIH1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein cornichon homolog 1 (CNIH1).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Protein cornichon homolog 1 (CNIH1).	[5]
Nabiximols	DMHKJ5I	Phase 3	Nabiximols increases the expression of Protein cornichon homolog 1 (CNIH1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein cornichon homolog 1 (CNIH1).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein cornichon homolog 1 (CNIH1).	[8]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Protein cornichon homolog 1 (CNIH1).	[9]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [8] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [9] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.