Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ9FAWS)

• DOT Name: VIP36-like protein (LMAN2L)
• Synonyms: Lectin mannose-binding 2-like; LMAN2-like protein
• Gene Name: LMAN2L
• Related Disease:
  Attention deficit hyperactivity disorder
  Bipolar depression
  Bipolar disorder
  Bronchopulmonary dysplasia
  Clear cell renal carcinoma
  Epilepsy
  Intellectual disability
  Papillary renal cell carcinoma
  Renal cell carcinoma
  Pulmonary emphysema
  Schizophrenia
  Autosomal recessive non-syndromic intellectual disability
  Intellectual developmental disorder, autosomal dominant 69
  Intellectual disability, autosomal recessive 52
• UniProt ID: LMA2L_HUMAN
• Pfam ID: PF03388
• Sequence:
  MAATLGPLGSWQQWRRCLSARDGSRMLLLLLLLGSGQGPQQVGAGQTFEYLKREHSLSKP
  YQGVGTGSSSLWNLMGNAMVMTQYIRLTPDMQSKQGALWNRVPCFLRDWELQVHFKIHGQ
  GKKNLHGDGLAIWYTKDRMQPGPVFGNMDKFVGLGVFVDTYPNEEKQQERVFPYISAMVN
  NGSLSYDHERDGRPTELGGCTAIVRNLHYDTFLVIRYVKRHLTIMMDIDGKHEWRDCIEV
  PGVRLPRGYYFGTSSITGDLSDNHDVISLKLFELTVERTPEEEKLHRDVFLPSVDNMKLP
  EMTAPLPPLSGLALFLIVFFSLVFSVFAIVIGIILYNKWQEQSRKRFY
• Function: May be involved in the regulation of export from the endoplasmic reticulum of a subset of glycoproteins. May function as a regulator of ERGIC-53.
• Tissue Specificity: Expressed in numerous tissues. Highest expression in skeletal muscle and kidney, intermediate levels in heart, liver and placenta, low levels in brain, thymus, spleen, small intestine and lung.
• Reactome Pathway:
  Cargo concentration in the ER (R-HSA-5694530)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[1]
Bipolar depression	DISA75FU	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Epilepsy	DISBB28L	Strong	Genetic Variation	[5]
Intellectual disability	DISMBNXP	Strong	Biomarker	[5]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[4]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[6]
Schizophrenia	DISSRV2N	moderate	Biomarker	[3]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[5]
Intellectual developmental disorder, autosomal dominant 69	DISZI4O2	Limited	Autosomal dominant	[7]
Intellectual disability, autosomal recessive 52	DIS1TMDP	Limited	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of VIP36-like protein (LMAN2L).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of VIP36-like protein (LMAN2L).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of VIP36-like protein (LMAN2L).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of VIP36-like protein (LMAN2L).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of VIP36-like protein (LMAN2L).	[14]

2 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 affects the methylation of VIP36-like protein (LMAN2L).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of VIP36-like protein (LMAN2L).	[13]

References

• [1] Bipolar disorder risk alleles in children with ADHD.J Neural Transm (Vienna). 2013 Nov;120(11):1611-7. doi: 10.1007/s00702-013-1035-8. Epub 2013 May 28.
• [2] Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
• [3] Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its interaction with ANK3 gene polymorphism.Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:157-62. doi: 10.1016/j.pnpbp.2014.05.017. Epub 2014 Jun 8.
• [4] Integrated molecular analysis of clear-cell renal cell carcinoma.Nat Genet. 2013 Aug;45(8):860-7. doi: 10.1038/ng.2699. Epub 2013 Jun 24.
• [5] Homozygous missense mutation in the LMAN2L gene segregates with intellectual disability in a large consanguineous Pakistani family. J Med Genet. 2016 Feb;53(2):138-44. doi: 10.1136/jmedgenet-2015-103179. Epub 2015 Nov 13.
• [6] Gene expression profile of human lung in a relatively early stage of COPD with emphysema.Int J Chron Obstruct Pulmon Dis. 2018 Aug 28;13:2643-2655. doi: 10.2147/COPD.S166812. eCollection 2018.
• [7] Dominant LMAN2L mutation causes intellectual disability with remitting epilepsy. Ann Clin Transl Neurol. 2019 Mar 7;6(4):807-811. doi: 10.1002/acn3.727. eCollection 2019 Apr.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] 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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.