Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLA7BAI)

• DOT Name: GS homeobox 2 (GSX2)
• Synonyms: Genetic-screened homeobox 2; Homeobox protein GSH-2
• Gene Name: GSX2
• Related Disease:
  Amyotrophic lateral sclerosis type 1
  Familial amyotrophic lateral sclerosis
  Hepatocellular carcinoma
  Neoplasm
  Diencephalic-mesencephalic junction dysplasia syndrome 2
• UniProt ID: GSX2_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSRSFYVDSLIIKDTSRPAPSLPEPHPGPDFFIPLGMPPPLVMSVSGPGCPSRKSGAFCV
  CPLCVTSHLHSSRGSVGAGSGGAGAGVTGAGGSGVAGAAGALPLLKGQFSSAPGDAQFCP
  RVNHAHHHHHPPQHHHHHHQPQQPGSAAAAAAAAAAAAAAAALGHPQHHAPVCTATTYNV
  ADPRRFHCLTMGGSDASQVPNGKRMRTAFTSTQLLELEREFSSNMYLSRLRRIEIATYLN
  LSEKQVKIWFQNRRVKHKKEGKGTQRNSHAGCKCVGSQVHYARSEDEDSLSPASANDDKE
  ISPL
• Function: Transcription factor that binds 5'-CNAATTAG-3' DNA sequence and regulates the expression of numerous genes including genes important for brain development. During telencephalic development, causes ventralization of pallial progenitors and, depending on the developmental stage, specifies different neuronal fates. At early stages, necessary and sufficient to correctly specify the ventral lateral ganglionic eminence (LGE) and its major derivatives, the striatal projection neurons. At later stages, may specify LGE progenitors toward dorsal LGE fates, including olfactory bulb interneurons.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[1]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Diencephalic-mesencephalic junction dysplasia syndrome 2	DIS1DL6Y	Limited	Autosomal recessive	[4]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of GS homeobox 2 (GSX2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of GS homeobox 2 (GSX2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of GS homeobox 2 (GSX2).	[7]

References

• [1] Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.J Neurochem. 2002 Jan;80(1):158-67. doi: 10.1046/j.0022-3042.2001.00683.x.
• [2] Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.PLoS One. 2014 Sep 30;9(9):e107876. doi: 10.1371/journal.pone.0107876. eCollection 2014.
• [3] Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas.Cell Physiol Biochem. 2018;47(1):428-439. doi: 10.1159/000489954. Epub 2018 May 18.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] 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.
• [7] 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.