Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8DF1WF)

• DOT Name: LIM/homeobox protein Lhx5 (LHX5)
• Synonyms: LIM homeobox protein 5
• Gene Name: LHX5
• Related Disease: Bipolar disorder
• UniProt ID: LHX5_HUMAN
• Pfam ID: PF00046 ; PF00412
• Sequence:
  MMVHCAGCERPILDRFLLNVLDRAWHIKCVQCCECKTNLSEKCFSREGKLYCKNDFFRRF
  GTKCAGCAQGISPSDLVRKARSKVFHLNCFTCMVCNKQLSTGEELYVIDENKFVCKDDYL
  SSSSLKEGSLNSVSSCTDRSLSPDLQDALQDDPKETDNSTSSDKETANNENEEQNSGTKR
  RGPRTTIKAKQLETLKAAFAATPKPTRHIREQLAQETGLNMRVIQVWFQNRRSKERRMKQ
  LSALGARRHAFFRSPRRMRPLGGRLDESEMLGSTPYTYYGDYQGDYYAPGSNYDFFAHGP
  PSQAQSPADSSFLAASGPGSTPLGALEPPLAGPHAADNPRFTDMISHPDTPSPEPGLPGT
  LHPMPGEVFSGGPSPPFPMSGTSGYSGPLSHPNPELNEAAVW
• Function: Plays an essential role in the regulation of neuronal differentiation and migration during development of the central nervous system.
• Tissue Specificity: Expressed in fetal brain and in various regions of the adult central nervous system including the spinal cord, the thalamus, and the cerebellum.
• KEGG Pathway: Sig.ling pathways regulating pluripotency of stem cells (hsa04550)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of LIM/homeobox protein Lhx5 (LHX5).	[2]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of LIM/homeobox protein Lhx5 (LHX5).	[4]

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 LIM/homeobox protein Lhx5 (LHX5).	[3]

References

• [1] Mutational analysis of two positional candidate susceptibility genes for bipolar disorder on chromosome 12q23-q24: phenylalanine hydroxylase and human LIM-homeobox LHX5.Psychiatr Genet. 2003 Jun;13(2):97-101. doi: 10.1097/01.ypg.0000057882.80011.9e.
• [2] 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.
• [3] 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.
• [4] 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.