Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXGFJ3F)

• DOT Name: Collectrin (CLTRN)
• Synonyms: Transmembrane protein 27
• Gene Name: CLTRN
• Related Disease:
  Hepatocellular carcinoma
  Clear cell renal carcinoma
  High blood pressure
  Neoplasm
  Dent disease
  Hartnup disease
• UniProt ID: CLTRN_HUMAN
• Pfam ID: PF16959
• Sequence:
  MLWLLFFLVTAIHAELCQPGAENAFKVRLSIRTALGDKAYAWDTNEEYLFKAMVAFSMRK
  VPNREATEISHVLLCNVTQRVSFWFVVTDPSKNHTLPAVEVQSAIRMNKNRINNAFFLND
  QTLEFLKIPSTLAPPMDPSVPIWIIIFGVIFCIIIVAIALLILSGIWQRRRKNKEPSEVD
  DAEDKCENMITIENGIPSDPLDMKGGHINDAFMTEDERLTPL
• Function: Plays an important role in amino acid transport by acting as binding partner of amino acid transporters SLC6A18 and SLC6A19, regulating their trafficking on the cell surface and their amino acid transporter activity. May also play a role in trafficking of amino acid transporters SLC3A1 and SLC7A9 to the renal cortical cell membrane. Regulator of SNARE complex function. Stimulator of beta cell replication.
• Tissue Specificity: Kidney; collecting ducts. Pancreas; beta cells of islets.
• Reactome Pathway: Insulin processing (R-HSA-264876)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[2]
High blood pressure	DISY2OHH	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Dent disease	DISRDLFN	moderate	Biomarker	[4]
Hartnup disease	DISYK0UH	Supportive	Autosomal recessive	[5]

12 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 Collectrin (CLTRN).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Collectrin (CLTRN).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Collectrin (CLTRN).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Collectrin (CLTRN).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Collectrin (CLTRN).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Collectrin (CLTRN).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Collectrin (CLTRN).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Collectrin (CLTRN).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Collectrin (CLTRN).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Collectrin (CLTRN).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Collectrin (CLTRN).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Collectrin (CLTRN).	[11]

References

• [1] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [2] Lack of TMEM27 expression is associated with postoperative progression of clinically localized conventional renal cell carcinoma.J Cancer Res Clin Oncol. 2016 Sep;142(9):1947-53. doi: 10.1007/s00432-016-2207-3. Epub 2016 Jul 14.
• [3] ACE2 and the Homolog Collectrin in the Modulation of Nitric Oxide and Oxidative Stress in Blood Pressure Homeostasis and Vascular Injury.Antioxid Redox Signal. 2017 Apr 20;26(12):645-659. doi: 10.1089/ars.2016.6950. Epub 2017 Jan 12.
• [4] Locus heterogeneity of Dent's disease: OCRL1 and TMEM27 genes in patients with no CLCN5 mutations.Pediatr Nephrol. 2009 Oct;24(10):1967-73. doi: 10.1007/s00467-009-1228-4. Epub 2009 Jul 7.
• [5] Loss of CLTRN function produces a neuropsychiatric disorder and a biochemical phenotype that mimics Hartnup disease. Am J Med Genet A. 2019 Dec;179(12):2459-2468. doi: 10.1002/ajmg.a.61357. Epub 2019 Sep 13.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [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] 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.