Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEUZH06)

• DOT Name: GTPase IMAP family member 4 (GIMAP4)
• Synonyms: Immunity-associated nucleotide 1 protein; IAN-1; hIAN1; Immunity-associated protein 4
• Gene Name: GIMAP4
• Related Disease:
  Asthma
  Immune system disorder
  Type-1 diabetes
• UniProt ID: GIMA4_HUMAN
• PDB ID: 3LXX
• Pfam ID: PF04548
• Sequence:
  MAAQYGSMSFNPSTPGASYGPGRQEPRNSQLRIVLVGKTGAGKSATGNSILGRKVFHSGT
  AAKSITKKCEKRSSSWKETELVVVDTPGIFDTEVPNAETSKEIIRCILLTSPGPHALLLV
  VPLGRYTEEEHKATEKILKMFGERARSFMILIFTRKDDLGDTNLHDYLREAPEDIQDLMD
  IFGDRYCALNNKATGAEQEAQRAQLLGLIQRVVRENKEGCYTNRMYQRAEEEIQKQTQAM
  QELHRVELEREKARIREEYEEKIRKLEDKVEQEKRKKQMEKKLAEQEAHYAVRQQRARTE
  VESKDGILELIMTALQIASFILLRLFAED
• Function: During thymocyte development, may play a role in the regulation of apoptosis. GTPase which exhibits a higher affinity for GDP than for GTP.
• Tissue Specificity: Highly expressed in spleen and peripheral blood leukocytes that contain mostly T- and B-lymphocytes. Expressed specifically in resting T- and B-lymphocytes and expression significantly decreases during B- or T-lymphocyte activation. Expressed at lower levels in thymus, ovary, colon and small intestine.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Limited	Biomarker	[1]
Immune system disorder	DISAEGPH	Limited	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[1]

2 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 GTPase IMAP family member 4 (GIMAP4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of GTPase IMAP family member 4 (GIMAP4).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GTPase IMAP family member 4 (GIMAP4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GTPase IMAP family member 4 (GIMAP4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GTPase IMAP family member 4 (GIMAP4).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of GTPase IMAP family member 4 (GIMAP4).	[6]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of GTPase IMAP family member 4 (GIMAP4).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GTPase IMAP family member 4 (GIMAP4).	[9]

References

• [1] GIMAP GTPase family genes: potential modifiers in autoimmune diabetes, asthma, and allergy.J Immunol. 2015 Jun 15;194(12):5885-94. doi: 10.4049/jimmunol.1500016. Epub 2015 May 11.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [7] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [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] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.