Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOR23GX)

• DOT Name: Placental protein 13-like (LGALS14)
• Synonyms: Charcot-Leyden crystal protein 2; CLC2; Galectin-14; Gal-14
• Gene Name: LGALS14
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Colitis
  Complete hydatidiform mole
  Constipation
  Cystic fibrosis
  Hepatocellular carcinoma
  Hyperaldosteronism
  Leukodystrophy
  Megalencephalic leukoencephalopathy with subcortical cysts
  Nervous system disease
  Non-alcoholic fatty liver disease
  Non-alcoholic steatohepatitis
  Parasitic infection
  Primary aldosteronism
  Ulcerative colitis
  Epilepsy, idiopathic generalized
  OPTN-related open angle glaucoma
  Familial hyperaldosteronism
  Glioma
  Opioid-induced constipation
• UniProt ID: PPL13_HUMAN
• PDB ID: 6K2Y; 6K2Z
• Pfam ID: PF00337
• Sequence:
  MSSLPVPYTLPVSLPVGSCVIITGTPILTFVKDPQLEVNFYTGMDEDSDIAFQFRLHFGH
  PAIMNSCVFGIWRYEEKCYYLPFEDGKPFELCIYVRHKEYKVMVNGQRIYNFAHRFPPAS
  VKMLQVFRDISLTRVLISD
• Function: Binds beta-galactoside and lactose. Strong inducer of T-cell apoptosis.
• Tissue Specificity: Highly expressed in placenta.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Complete hydatidiform mole	DIS5QPI0	Strong	Biomarker	[3]
Constipation	DISRQXWI	Strong	Biomarker	[4]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Hyperaldosteronism	DIS3WGAL	Strong	Genetic Variation	[7]
Leukodystrophy	DISVY1TT	Strong	Biomarker	[8]
Megalencephalic leukoencephalopathy with subcortical cysts	DISK9A1M	Strong	Biomarker	[8]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[9]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[10]
Non-alcoholic steatohepatitis	DIST4788	Strong	Altered Expression	[10]
Parasitic infection	DISX9CEW	Strong	Biomarker	[11]
Primary aldosteronism	DISOEFNH	Strong	Biomarker	[12]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[2]
Epilepsy, idiopathic generalized	DISODZC9	moderate	Genetic Variation	[13]
OPTN-related open angle glaucoma	DISDR98A	Disputed	Biomarker	[14]
Familial hyperaldosteronism	DIS9R9LI	Limited	Genetic Variation	[15]
Glioma	DIS5RPEH	Limited	Biomarker	[16]
Opioid-induced constipation	DIS0D2NT	Limited	Biomarker	[17]

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 increases the methylation of Placental protein 13-like (LGALS14).	[18]

References

• [1] Lubiprostone as a potential therapeutic agent to improve intestinal permeability and prevent the development of atherosclerosis in apolipoprotein E-deficient mice.PLoS One. 2019 Jun 17;14(6):e0218096. doi: 10.1371/journal.pone.0218096. eCollection 2019.
• [2] Chloride channel ClC-2 is a key factor in the development of DSS-induced murine colitis.Inflamm Bowel Dis. 2013 Dec;19(13):2867-77. doi: 10.1097/MIB.0b013e3182a82ae9.
• [3] Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles.Int J Mol Sci. 2019 Oct 10;20(20):4999. doi: 10.3390/ijms20204999.
• [4] Lubiprostone activates Cl- secretion via cAMP signaling and increases membrane CFTR in the human colon carcinoma cell line, T84.Dig Dis Sci. 2011 Feb;56(2):339-51. doi: 10.1007/s10620-010-1495-8. Epub 2010 Dec 8.
• [5] CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity.BMC Med Genet. 2004 Oct 26;5:26. doi: 10.1186/1471-2350-5-26.
• [6] Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up-Regulating Galectin-14.PLoS One. 2016 Aug 5;11(8):e0160822. doi: 10.1371/journal.pone.0160822. eCollection 2016.
• [7] Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.Curr Hypertens Rep. 2019 Apr 4;21(4):31. doi: 10.1007/s11906-019-0934-y.
• [8] Leukoencephalopathy-causing CLCN2 mutations are associated with impaired Cl(-) channel function and trafficking.J Physiol. 2017 Nov 15;595(22):6993-7008. doi: 10.1113/JP275087. Epub 2017 Oct 9.
• [9] Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurol. 2013 Jul;12(7):659-68. doi: 10.1016/S1474-4422(13)70053-X. Epub 2013 May 22.
• [10] Lack of ClC-2 Alleviates High Fat Diet-Induced Insulin Resistance and Non-Alcoholic Fatty Liver Disease.Cell Physiol Biochem. 2018;45(6):2187-2198. doi: 10.1159/000488164. Epub 2018 Mar 10.
• [11] Proteomic identification of galectin-11 and 14 ligands from Haemonchus contortus.PeerJ. 2018 Mar 19;6:e4510. doi: 10.7717/peerj.4510. eCollection 2018.
• [12] Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism.Nat Commun. 2019 Oct 15;10(1):4678. doi: 10.1038/s41467-019-12113-9.
• [13] Regulation of ClC-2 gating by intracellular ATP.Pflugers Arch. 2013 Oct;465(10):1423-37. doi: 10.1007/s00424-013-1286-0. Epub 2013 May 1.
• [14] Effect of CLC-2 on the cytoskeleton in human trabecular meshwork cells.Mol Med Rep. 2013 Oct;8(4):1099-105. doi: 10.3892/mmr.2013.1619. Epub 2013 Aug 7.
• [15] Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation.Nat Commun. 2019 Nov 14;10(1):5155. doi: 10.1038/s41467-019-13033-4.
• [16] Expression of voltage-gated chloride channels in human glioma cells.J Neurosci. 2003 Jul 2;23(13):5572-82. doi: 10.1523/JNEUROSCI.23-13-05572.2003.
• [17] Analysis of Nausea in Clinical Studies of Lubiprostone for the Treatment of Constipation Disorders.Dig Dis Sci. 2017 Dec;62(12):3568-3578. doi: 10.1007/s10620-017-4680-1. Epub 2017 Aug 28.
• [18] 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.