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COVID-19 research

Gene: IDE

Amber List (moderate evidence)

IDE (insulin degrading enzyme)
EnsemblGeneIds (GRCh38): ENSG00000119912
EnsemblGeneIds (GRCh37): ENSG00000119912
OMIM: 146680, Gene2Phenotype
IDE is in 1 panel

2 reviews

Alison Coffey (Illumina Clinical Services Laboratory, Illumina Inc.)

I don't know

Evidence Summary from Illumina curation team: Insulin-degrading enzyme (IDE), also known as insulysin, is a member of the zinc metalloproteinase family that was initially implicated in insulin degradation. It is highly conserved among different species and has the ability to interact with a variety of functionally unrelated ligands that share little homology in their primary amino acid sequences. Several human viruses use enzymes as receptors. Li et al. (2006) (PMID 17055432) established IDE as a cellular receptor for both cell-free and cell-associated Varicella-zoster virus (VZV), the cause of chickenpox and shingles in humans. VZV is likely spread as cell-free virus to susceptible hosts but transmitted by cell-to-cell spread in the body and in vitro. Li et al. (2006) showed that IDE interacts with the VZV glycoprotein E (gE) (which is essential for virus infection) through its extracellular domain. Downregulation of IDE by siRNA, or blocking of IDE with antibody, with soluble IDE protein extracted from liver, or with bacitracin inhibited VZV infection. Cell-to-cell spread of virus was also impaired by blocking IDE. Transfection of cell lines impaired for VZV infection with a plasmid expressing human IDE resulted in increased entry and enhanced infection with cell-free and cell-associated virus. Li et al. (2010) subsequently reported that a recombinant soluble IDE (rIDE) enhanced VZV infectivity at an early step of infection associated with an increase in virus internalization, and increased cell-to-cell spread. In 2017, Hahn et al. demonstrated that mature HIV-1 p6 protein (stability of which inversely affects the replication capacity of HIV-1) is a substrate for IDE. IDE is both sufficient and required for the degradation of p6, which is approximately 100-fold more efficiently degraded by IDE than its eponymous substrate insulin. An IDE specific inhibitor, 6bK, and exogenous insulin, were both shown to interfere with X4-tropic HIV-1 replication in activated PBMCs, most probably by competing with p6 for degradation by IDE. In addition, an IDE-insensitive p6 mutant of HIV-1 exhibits impaired replication capacity but is insensitive to treatment with insulin or 6bK. Conversely, neither virus release and maturation, nor the amounts of particle associated Vpr and p6 itself were altered in IDE knock out cells. The data support a model in which IDE is responsible for the rapid degradation of p6 entering the cell as part of the incoming virion, a process that appears to be crucial to achieve optimal X4-tropic virus replication.
Created: 28 May 2020, 3:12 p.m. | Last Modified: 28 May 2020, 3:12 p.m.
Panel Version: 0.347

Publications

Rebecca Foulger (Genomics England curator)

Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
Created: 28 May 2020, 12:36 p.m. | Last Modified: 28 May 2020, 12:36 p.m.
Panel Version: 0.336

Details

Mode of Inheritance
Unknown
Sources
OMIM
146680
Clinvar variants
Variants in IDE
Penetrance
None
Panels with this gene

History Filter Activity

28 May 2020, Gel status: 2

Created, Added New Source, Set mode of inheritance

Rebecca Foulger (Genomics England curator)

gene: IDE was added gene: IDE was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber Mode of inheritance for gene: IDE was set to Unknown