IDE: Insulin-Degrading Enzyme
A key zinc metallopeptidase involved in insulin and amyloid-beta degradation, with implications in diabetes and Alzheimer's disease.
Gene Information Card
| Symbol | IDE |
|---|---|
| Full Name | Insulin-Degrading Enzyme |
| Gene Type | Protein-coding |
| Chromosomal Location | 10q23.31 |
| NCBI Gene ID | 3416 ncbi.nlm.nih.gov/gene/3416 |
| Ensembl ID | ENSG00000119912 |
| UniProt ID | P14735 |
| OMIM ID | 146680 |
| HGNC ID | 5381 |
| Aliases | INSI, INSULYSIN, AD, FLJ35948, MGC10667 |
Description
The IDE gene encodes insulin-degrading enzyme, a zinc metallopeptidase that cleaves small peptides such as insulin, glucagon, and amyloid-beta. It plays a critical role in insulin clearance and is implicated in type 2 diabetes and Alzheimer's disease due to its ability to degrade amyloid-beta peptides. The gene is located on chromosome 10q23.31 and is expressed in multiple tissues, with highest levels in the liver, kidney, and brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's Disease | Reduced IDE activity leads to accumulation of amyloid-beta plaques in the brain; genetic variants may alter amyloid-beta degradation. | ClinVar, OMIM |
| Type 2 Diabetes | IDE degrades insulin; impaired function contributes to hyperinsulinemia and insulin resistance. | NCBI Gene, OMIM |
| Cancer (various) | IDE expression is altered in some cancers; may affect insulin-like growth factor signaling. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 32.5 | High |
| Kidney | 28.1 | High |
| Brain | 18.7 | Medium |
| Pancreas | 15.3 | Medium |
| Heart | 12.0 | Medium |
| Lung | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 35.2 | High expression |
| HEK293 (embryonic kidney) | 30.8 | High expression |
| SH-SY5Y (neuroblastoma) | 22.4 | Medium expression |
| MCF7 (breast cancer) | 14.1 | Medium expression |
| A549 (lung cancer) | 9.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.220A>G (p.Ile74Val) | Missense | 0.5% in European populations | Reduced enzymatic activity; associated with Alzheimer's risk |
| c.1120C>T (p.Arg374Cys) | Missense | Rare | Decreased insulin degradation; linked to type 2 diabetes |
| c.1582G>A (p.Glu528Lys) | Missense | <0.1% | Altered substrate specificity; potential gain-of-function |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Ile74Val reduce IDE catalytic activity, impairing insulin and amyloid-beta clearance, contributing to diabetes and Alzheimer's pathology.
Gain of Function (GOF)
Rare variants like p.Glu528Lys may enhance degradation of certain peptides, potentially altering hormone signaling.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for IDE.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Insulin processing and degradation (Reactome: R-HSA-264876)
• Alzheimer's disease and amyloid-beta clearance (KEGG: hsa05010)
• Peptide hormone metabolism (Reactome: R-HSA-2980736)
Protein Summary
Insulin-degrading enzyme (IDE) is a 110-kDa zinc metallopeptidase localized primarily in the cytosol, but also found in peroxisomes, endosomes, and extracellular space. It degrades multiple bioactive peptides including insulin, glucagon, atrial natriuretic peptide, and amyloid-beta. IDE has a clam-shaped structure with a catalytic zinc-binding site. Its activity is regulated by ATP, redox state, and substrate-induced conformational changes. Dysregulation of IDE is linked to metabolic and neurodegenerative disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CIDEA Knockout HEK293 Cell Line | EDJ-KQ1182 | Human | 1149 | Details Get a Quote |
| IDE Knockout HEK293 Cell Line | EDJ-KQ4962 | Human | 3416 | Details Get a Quote |
| MIDEAS Knockout HEK293 Cell Line | EDJ-KQ10059 | Human | 91748 | Details Get a Quote |
| CIDEC Knockout HEK293 Cell Line | EDJ-KQ11944 | Human | 63924 | Details Get a Quote |
| IDE Knockout HCT 116 Cell Line | EDJ-KQ26618 | Human | 3416 | Details Get a Quote |
| IDE Knockout A-549 Cell Line | EDJ-KQ27837 | Human | 3416 | Details Get a Quote |
| IDE Knockout HeLa Cell Line | EDJ-KQ27838 | Human | 3416 | Details Get a Quote |
| MIDEAS Knockout A-549 Cell Line | EDJ-KQ38392 | Human | 91748 | Details Get a Quote |
| MIDEAS Knockout HCT 116 Cell Line | EDJ-KQ38394 | Human | 91748 | Details Get a Quote |
| MIDEAS Knockout HeLa Cell Line | EDJ-KQ38395 | Human | 91748 | Details Get a Quote |
| CIDEC Knockout A-549 Cell Line | EDJ-KQ40457 | Human | 63924 | Details Get a Quote |
| CIDEB Knockout HEK293 Cell Line | EDJ-KQ51206 | Human | 27141 | Details Get a Quote |
| CIDEA Knockout HeLa Cell Line | EDJ-KQ52911 | Human | 1149 | Details Get a Quote |
| CIDEB Knockout HeLa Cell Line | EDJ-KQ56012 | Human | 27141 | Details Get a Quote |
| CIDEC Knockout HeLa Cell Line | EDJ-KQ56997 | Human | 63924 | Details Get a Quote |
Displaying Records 1 To 15 Of 20 Records
