DIO1 (iodothyronine deiodinase 1)

Gene

• Entrez ID: 1733
• Gene name: Iodothyronine deiodinase 1
• Gene symbol: DIO1
• Synonyms (NCBI Gene): 5DI, THMA2, TXDI1
• Chromosome: 1
• Chromosome location: 1p32.3
• Summary: The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversio

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006136	hsa-miR-224-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006136	hsa-miR-224-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006137	hsa-miR-383-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006137	hsa-miR-383-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006136	hsa-miR-224-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006136	hsa-miR-224-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006137	hsa-miR-383-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006136	hsa-miR-224-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006136	hsa-miR-224-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT006137	hsa-miR-383-5p	Luciferase reporter assay, qRT-PCR, Western blot	21912701
MIRT017647	hsa-miR-335-5p	Microarray	18185580
MIRT936582	hsa-miR-3688-3p	CLIP-seq
MIRT936583	hsa-miR-4261	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004800	Function	Thyroxine 5'-deiodinase activity	IBA
GO:0004800	Function	Thyroxine 5'-deiodinase activity	IDA	12586771, 32718224
GO:0004800	Function	Thyroxine 5'-deiodinase activity	IEA
GO:0004800	Function	Thyroxine 5'-deiodinase activity	TAS	1400883
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006520	Process	Amino acid metabolic process	IGI	26305885
GO:0006590	Process	Thyroid hormone generation	TAS	1400883
GO:0008430	Function	Selenium binding	TAS	1400883
GO:0016020	Component	Membrane	IEA
GO:0016323	Component	Basolateral plasma membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0033798	Function	Thyroxine 5-deiodinase activity	IDA	32718224
GO:0033798	Function	Thyroxine 5-deiodinase activity	IEA
GO:0042403	Process	Thyroid hormone metabolic process	IBA
GO:0042403	Process	Thyroid hormone metabolic process	IEA
GO:0042404	Process	Thyroid hormone catabolic process	IDA	12586771, 32718224
GO:0042404	Process	Thyroid hormone catabolic process	IEA
GO:0042446	Process	Hormone biosynthetic process	IEA

Other IDs

• MIM: 147892
• HGNC: 2883
• e!Ensembl: ENSG00000211452

Protein

• UniProt ID: P49895
• Protein name: Type I iodothyronine deiodinase (EC 1.21.99.3) (EC 1.21.99.4) (5DI) (DIOI) (Type 1 DI) (Type-I 5'-deiodinase)
• Protein function: Plays a crucial role in the metabolism of thyroid hormones (TH) and has specific roles in TH activation and inactivation by deiodination (PubMed:12586771, PubMed:32718224, PubMed:18821722). Catalyzes the deiodination of L-thyroxine (T4) to 3,5,3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00837	T4_deiodinase	8 → 248	Iodothyronine deiodinase	Family

• Sequence:

  MGLPQPGLWLKRLWVLLEVAVHVVVGKVLLILFPDRVKRNILAMGEKTGMTRNPHFSHDN
  WIPTFFSTQYFWFVLKVRWQRLEDTTELGGLAPNCPVVRLSGQRCNIWEFMQGNRPLVLN
  FGSCTUPSFMFKFDQFKRLIEDFSSIADFLVIYIEEAHASDGWAFKNNMDIRNHQNLQDR
  LQAAHLLLARSPQCPVVVDTMQNQSSQLYAALPERLYIIQEGRILYKGKSGPWNYNPEEV
  RAVLEKLHS

• Sequence length: 249

Pathways

KEGG:

Hormone signaling
Thyroid hormone signaling pathway

Reactome:

Regulation of thyroid hormone activity

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Thyroid hormone metabolism, abnormal, 2	Pathogenic	rs754694815, rs201420507	RCV002248330 RCV002248331	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
HYPERTHYROXINEMIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Levothyroxine response	drug response	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE MYELOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROID DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations