Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZO19Y)

• DOT Name: GTPase IMAP family member 7 (GIMAP7)
• Synonyms: Immunity-associated nucleotide 7 protein; IAN-7
• Gene Name: GIMAP7
• Related Disease:
  Autoimmune disease
  Type-1 diabetes
  Oral cancer
• UniProt ID: GIMA7_HUMAN
• PDB ID: 3ZJC
• Pfam ID: PF04548
• Sequence:
  MAESEDRSLRIVLVGKTGSGKSATANTILGEEIFDSRIAAQAVTKNCQKASREWQGRDLL
  VVDTPGLFDTKESLDTTCKEISRCIISSCPGPHAIVLVLLLGRYTEEEQKTVALIKAVFG
  KSAMKHMVILFTRKEELEGQSFHDFIADADVGLKSIVKECGNRCCAFSNSKKTSKAEKES
  QVQELVELIEKMVQCNEGAYFSDDIYKDTEERLKQREEVLRKIYTDQLNEEIKLVEEDKH
  KSEEEKEKEIKLLKLKYDEKIKNIREEAERNIFKDVFNRIWKMLSEIWHRFLSKCKFYSS
• Function: The dimer has GTPase activity; the active site contains residues from both subunits.
• Tissue Specificity: Most abundantly expressed in spleen, lymph nodes, and fetal kidney, but also present in the heart and the small intestine. Lower expression levels are found in lung, kidney, liver, and thyroid, salivary, and mammary glands. Also detected in the thymus . Detected in T-cells .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[1]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[2]
Oral cancer	DISLD42D	Limited	Altered Expression	[3]

3 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 GTPase IMAP family member 7 (GIMAP7).	[4]
Marinol	DM70IK5	Approved	Marinol increases the expression of GTPase IMAP family member 7 (GIMAP7).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of GTPase IMAP family member 7 (GIMAP7).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of GTPase IMAP family member 7 (GIMAP7).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of GTPase IMAP family member 7 (GIMAP7).	[8]

References

• [1] IAN5 polymorphisms are associated with systemic lupus erythematosus.Lupus. 2009 Oct;18(12):1045-52. doi: 10.1177/0961203309106830.
• [2] Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene.Genome Res. 2002 Jul;12(7):1029-39. doi: 10.1101/gr.412702.
• [3] Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach.Pathol Oncol Res. 2020 Jul;26(3):1817-1822. doi: 10.1007/s12253-019-00775-1. Epub 2019 Nov 20.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [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.