DIO1: Iodothyronine Deiodinase 1
Key regulator of thyroid hormone metabolism and homeostasis
Gene Information Card
| Symbol | DIO1 |
|---|---|
| Full Name | Iodothyronine Deiodinase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p32.3 |
| NCBI Gene ID | 1733 ncbi.nlm.nih.gov/gene/1733 |
| Ensembl ID | ENSG00000100219 |
| UniProt ID | P49895 |
| OMIM ID | 147892 |
| HGNC ID | 2885 |
| Aliases | DIO1, ITDI1, TXDI1 |
Description
The DIO1 gene encodes iodothyronine deiodinase type 1 (D1), a selenoenzyme that catalyzes the deiodination of thyroxine (T4) to the active triiodothyronine (T3) and reverse T3 (rT3) to diiodothyronine (T2). D1 is expressed primarily in liver, kidney, and thyroid, and plays a critical role in systemic thyroid hormone homeostasis. Mutations in DIO1 can alter thyroid hormone levels and are associated with abnormal thyroid function tests.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperthyroidism | Increased DIO1 activity leads to elevated T3 production, exacerbating thyrotoxicosis | ClinVar, PMID: 25683116 |
| Hypothyroidism | Reduced DIO1 activity impairs T4-to-T3 conversion, contributing to low T3 syndrome | ClinVar, PMID: 23418333 |
| Resistance to Thyroid Hormone Beta | Altered DIO1 expression modifies T3 availability, modulating clinical phenotype | OMIM #188570 |
| Type 2 Diabetes | DIO1 polymorphisms associated with insulin resistance and altered thyroid hormone metabolism | PMID: 29127259 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Thyroid | 6.1 | Medium |
| Placenta | 2.4 | Low |
| Skeletal Muscle | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte cell line, high DIO1 activity |
| HEK293 | 3.1 | Low endogenous expression |
| THP-1 | 1.5 | Monocytic cell line, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.785G>A (p.Arg262His) | Missense | 0.01% | Reduced catalytic activity, altered T3/T4 ratio |
| c.1120C>T (p.Arg374Cys) | Missense | 0.005% | Decreased enzyme stability, impaired deiodination |
| c.1369G>A (p.Gly457Arg) | Missense | 0.002% | Loss of function, associated with low T3 syndrome |
Mutation functional classification
Loss of Function (LOF)
Missense variants such as p.Arg262His and p.Arg374Cys reduce D1 catalytic efficiency and stability, leading to impaired T4-to-T3 conversion.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in DIO1.
Dominant Negative (DN)
No dominant-negative effects documented for DIO1 mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Thyroid hormone synthesis and metabolism (Reactome: R-HSA-209968)
• Selenium micronutrient network (WikiPathways: WP15)
Protein Summary
Iodothyronine deiodinase type 1 (D1) is a 249-amino acid selenoprotein containing a selenocysteine residue at the active site. It is anchored to the endoplasmic reticulum membrane via a transmembrane domain. D1 catalyzes the outer-ring deiodination of T4 to T3 and inner-ring deiodination of rT3 to T2, using reduced thioredoxin as a cofactor. The enzyme is essential for maintaining circulating T3 levels and is regulated by thyroid status, selenium availability, and various drugs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DIO1 Knockout HEK293 Cell Line | EDJ-KQ4443 | Human | 1733 | Details Get a Quote |
| DIO1 Knockout HeLa Cell Line | EDJ-KQ53091 | Human | 1733 | Details Get a Quote |
| DIO1 Knockout A-549 Cell Line | EDJ-KQ61558 | Human | 1733 | Details Get a Quote |
| DIO1 Knockout HCT 116 Cell Line | EDJ-KQ70049 | Human | 1733 | Details Get a Quote |
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