IDE

insulin degrading enzyme, the group of M16 metallopeptidases

Basic information

Region (hg38): 10:92451683-92574096

Links

ENSG00000119912 ∙ NCBI:3416 ∙ OMIM:146680 ∙ HGNC:5381 ∙ Uniprot:P14735 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IDE gene.

• Inborn genetic diseases (33 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IDE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			32	1		33
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	32	3	2

Variants in IDE

This is a list of pathogenic ClinVar variants found in the IDE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-92455608-T-C		not specified	Likely benign (Dec 02, 2021)
10-92456365-C-A		not specified	Uncertain significance (Nov 17, 2022)
10-92456389-C-T		not specified	Uncertain significance (Apr 13, 2022)
10-92461235-A-G		not specified	Uncertain significance (Aug 17, 2022)
10-92463758-T-C		not specified	Uncertain significance (Dec 20, 2023)
10-92463774-T-G		not specified	Uncertain significance (Nov 15, 2021)
10-92463969-A-G			Benign (Jul 04, 2018)
10-92465791-G-T			Benign (Mar 30, 2018)
10-92465811-C-T		not specified	Uncertain significance (May 04, 2022)
10-92468939-G-A		not specified	Uncertain significance (Feb 21, 2024)
10-92468974-A-G		not specified	Uncertain significance (Nov 08, 2022)
10-92468981-C-G		not specified	Uncertain significance (Dec 03, 2021)
10-92470313-G-A		not specified	Uncertain significance (Feb 28, 2023)
10-92470321-G-C		not specified	Uncertain significance (Jan 04, 2022)
10-92475918-A-G		not specified	Uncertain significance (Feb 21, 2024)
10-92475975-T-C		not specified	Uncertain significance (Jun 07, 2023)
10-92479332-G-A		not specified	Uncertain significance (Feb 13, 2023)
10-92479353-G-A		not specified	Uncertain significance (Nov 18, 2022)
10-92483287-C-A		not specified	Uncertain significance (Aug 02, 2023)
10-92487200-A-G		not specified	Uncertain significance (Jun 13, 2023)
10-92487221-G-A		not specified	Uncertain significance (Mar 29, 2022)
10-92490495-T-C		not specified	Uncertain significance (May 11, 2022)
10-92490506-T-A		not specified	Uncertain significance (Aug 21, 2023)
10-92490570-C-T		not specified	Uncertain significance (Nov 17, 2022)
10-92490576-A-C		not specified	Uncertain significance (Feb 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IDE	protein_coding	protein_coding	ENST00000265986	25	122393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00663	0.993	125694	0	52	125746	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.08	396	531	0.746	0.0000268	6722
Missense in Polyphen		108	183.07	0.58995		2350
Synonymous	0.791	172	186	0.926	0.00000952	1834
Loss of Function	5.17	16	58.7	0.273	0.00000301	751

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000499	0.000489
Ashkenazi Jewish	0.000400	0.000397
East Asian	0.000109	0.000109
Finnish	0.000326	0.000323
European (Non-Finnish)	0.000213	0.000211
Middle Eastern	0.000109	0.000109
South Asian	0.000134	0.000131
Other	0.000348	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia. {ECO:0000269|PubMed:10684867, ECO:0000269|PubMed:17613531, ECO:0000269|PubMed:18986166}.
• Pathway: Alzheimer,s disease - Homo sapiens (human);Alzheimers Disease;Post-translational protein modification;Metabolism of proteins;Peroxisomal protein import;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.443

Intolerance Scores

• loftool: 0.797
• rvis_EVS: -1.53
• rvis_percentile_EVS: 3.39

Haploinsufficiency Scores

• pHI: 0.838
• hipred: Y
• hipred_score: 0.706
• ghis: 0.640

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ide
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: ide
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: proteolysis;protein targeting to peroxisome;insulin receptor signaling pathway;determination of adult lifespan;bradykinin catabolic process;ubiquitin recycling;positive regulation of protein oligomerization;hormone catabolic process;positive regulation of protein catabolic process;negative regulation of proteolysis;viral entry into host cell;amyloid-beta metabolic process;protein homooligomerization;protein homotetramerization;protein heterooligomerization;proteolysis involved in cellular protein catabolic process;amyloid-beta clearance;insulin metabolic process;insulin catabolic process;regulation of aerobic respiration
• Cellular component: extracellular space;nucleus;cytoplasm;mitochondrion;peroxisome;peroxisomal matrix;cytosol;external side of plasma membrane;cell surface;basolateral plasma membrane;cytosolic proteasome complex
• Molecular function: amyloid-beta binding;virus receptor activity;metalloendopeptidase activity;signaling receptor binding;protein binding;ATP binding;zinc ion binding;ATPase activity;beta-endorphin binding;peptide binding;protein homodimerization activity;insulin binding;ubiquitin-dependent protein binding