Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6WI2XS)

• DOT Name: LIM/homeobox protein Lhx1 (LHX1)
• Synonyms: LIM homeobox protein 1; Homeobox protein Lim-1; hLim-1
• Gene Name: LHX1
• Related Disease:
  Clear cell renal carcinoma
  Medulloblastoma
  Multicystic dysplastic kidney
  Neoplasm
  Renal dysplasia
  Von hippel-lindau disease
  Wilms tumor
  Renal cell carcinoma
• UniProt ID: LHX1_HUMAN
• Pfam ID: PF00046 ; PF00412
• Sequence:
  MVHCAGCKRPILDRFLLNVLDRAWHVKCVQCCECKCNLTEKCFSREGKLYCKNDFFRCFG
  TKCAGCAQGISPSDLVRRARSKVFHLNCFTCMMCNKQLSTGEELYIIDENKFVCKEDYLS
  NSSVAKENSLHSATTGSDPSLSPDSQDPSQDDAKDSESANVSDKEAGSNENDDQNLGAKR
  RGPRTTIKAKQLETLKAAFAATPKPTRHIREQLAQETGLNMRVIQVWFQNRRSKERRMKQ
  LSALGARRHAFFRSPRRMRPLVDRLEPGELIPNGPFSFYGDYQSEYYGPGGNYDFFPQGP
  PSSQAQTPVDLPFVPSSGPSGTPLGGLEHPLPGHHPSSEAQRFTDILAHPPGDSPSPEPS
  LPGPLHSMSAEVFGPSPPFSSLSVNGGASYGNHLSHPPEMNEAAVW
• Function: Potential transcription factor. May play a role in early mesoderm formation and later in lateral mesoderm differentiation and neurogenesis.
• Tissue Specificity: Expressed in the brain, thymus, and tonsils. Expressed in samples from patients with chronic myeloid leukemia (CML) and in 58% of acute myeloid leukemia (AML) cell lines.
• Reactome Pathway: Formation of intermediate mesoderm (R-HSA-9761174)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[2]
Multicystic dysplastic kidney	DISJ9R1F	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Renal dysplasia	DIS3DFGD	Strong	Altered Expression	[3]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Altered Expression	[1]
Wilms tumor	DISB6T16	Strong	Altered Expression	[3]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[1]

6 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 LIM/homeobox protein Lhx1 (LHX1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of LIM/homeobox protein Lhx1 (LHX1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of LIM/homeobox protein Lhx1 (LHX1).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of LIM/homeobox protein Lhx1 (LHX1).	[7]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of LIM/homeobox protein Lhx1 (LHX1).	[7]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of LIM/homeobox protein Lhx1 (LHX1).	[9]

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 Lhx1 (LHX1).	[8]

References

• [1] The Lim1 oncogene as a new therapeutic target for metastatic human renal cell carcinoma.Oncogene. 2019 Jan;38(1):60-72. doi: 10.1038/s41388-018-0413-y. Epub 2018 Aug 3.
• [2] Functional genomics identifies drivers of medulloblastoma dissemination.Cancer Res. 2012 Oct 1;72(19):4944-53. doi: 10.1158/0008-5472.CAN-12-1629. Epub 2012 Aug 8.
• [3] Lim1, an embryonal transcription factor, is absent in multicystic renal dysplasia, but reactivated in nephroblastomas.Pathobiology. 2011;78(4):210-9. doi: 10.1159/000326769. Epub 2011 Jul 19.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [8] 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.
• [9] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.