DIO3 (iodothyronine deiodinase 3)

Gene

• Entrez ID: 1735
• Gene name: Iodothyronine deiodinase 3
• Gene symbol: DIO3
• Synonyms (NCBI Gene): 5DIII, D3, DIOIII, TXDI3
• Chromosome: 14
• Chromosome location: 14q32.31
• Summary: The protein encoded by this intronless gene belongs to the iodothyronine deiodinase family. It catalyzes the inactivation of thyroid hormone by inner ring deiodination of the prohormone thyroxine (T4) and the bioactive hormone 3,3`,5-triiodothyronine (T3)

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT936621	hsa-let-7a	CLIP-seq
MIRT936622	hsa-let-7b	CLIP-seq
MIRT936623	hsa-let-7c	CLIP-seq
MIRT936624	hsa-let-7d	CLIP-seq
MIRT936625	hsa-let-7e	CLIP-seq
MIRT936626	hsa-let-7f	CLIP-seq
MIRT936627	hsa-let-7g	CLIP-seq
MIRT936628	hsa-let-7i	CLIP-seq
MIRT936629	hsa-miR-1206	CLIP-seq
MIRT936630	hsa-miR-1321	CLIP-seq
MIRT936631	hsa-miR-1915	CLIP-seq
MIRT936632	hsa-miR-3175	CLIP-seq
MIRT936633	hsa-miR-4270	CLIP-seq
MIRT936634	hsa-miR-4441	CLIP-seq
MIRT936635	hsa-miR-4445	CLIP-seq
MIRT936636	hsa-miR-4458	CLIP-seq
MIRT936637	hsa-miR-4500	CLIP-seq
MIRT936638	hsa-miR-4726-3p	CLIP-seq
MIRT936639	hsa-miR-4739	CLIP-seq
MIRT936640	hsa-miR-4756-5p	CLIP-seq
MIRT936641	hsa-miR-935	CLIP-seq
MIRT936642	hsa-miR-98	CLIP-seq
MIRT1977151	hsa-miR-1301	CLIP-seq
MIRT1977152	hsa-miR-3162-3p	CLIP-seq
MIRT1977153	hsa-miR-3614-5p	CLIP-seq
MIRT1977154	hsa-miR-3616-3p	CLIP-seq
MIRT1977155	hsa-miR-3944-5p	CLIP-seq
MIRT1977156	hsa-miR-4660	CLIP-seq
MIRT1977157	hsa-miR-4721	CLIP-seq
MIRT1977158	hsa-miR-4734	CLIP-seq
MIRT1977159	hsa-miR-5047	CLIP-seq
MIRT1977160	hsa-miR-593	CLIP-seq
MIRT1977161	hsa-miR-647	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IEA
GO:0004800	Function	Thyroxine 5'-deiodinase activity	IBA
GO:0004800	Function	Thyroxine 5'-deiodinase activity	IEA
GO:0004800	Function	Thyroxine 5'-deiodinase activity	NAS	7593630
GO:0004800	Function	Thyroxine 5'-deiodinase activity	TAS
GO:0005768	Component	Endosome	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006915	Process	Apoptotic process	IEA
GO:0010008	Component	Endosome membrane	IEA
GO:0016020	Component	Membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0033798	Function	Thyroxine 5-deiodinase activity	IDA	12746313, 18566113
GO:0033798	Function	Thyroxine 5-deiodinase activity	IEA
GO:0040018	Process	Positive regulation of multicellular organism growth	IEA
GO:0042403	Process	Thyroid hormone metabolic process	IBA
GO:0042403	Process	Thyroid hormone metabolic process	IGI	26305885
GO:0042403	Process	Thyroid hormone metabolic process	TAS
GO:0042404	Process	Thyroid hormone catabolic process	IDA	12746313
GO:0042404	Process	Thyroid hormone catabolic process	IEA
GO:0042446	Process	Hormone biosynthetic process	IEA
GO:0046549	Process	Retinal cone cell development	IEA
GO:0070342	Process	Brown fat cell proliferation	IEA
GO:0097474	Process	Retinal cone cell apoptotic process	IEA

Other IDs

• MIM: 601038
• HGNC: 2885
• e!Ensembl: ENSG00000197406

Protein

• UniProt ID: P55073
• Protein name: Thyroxine 5-deiodinase (EC 1.21.99.3) (5DIII) (DIOIII) (Type 3 DI) (Type III iodothyronine 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:7593630, PubMed:12586771, PubMed:12746313, PubMed:18821722). Catalyzes the deiodination of L-thyroxi
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00837	T4_deiodinase	38 → 293	Iodothyronine deiodinase	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in placenta and several fetal tissues. {ECO:0000269|PubMed:7593630}.
• Sequence:

  MPRQATSRLVVGEGEGSQGASGPAATMLRSLLLHSLRLCAQTASCLVLFPRFLGTAFMLW
  LLDFLCIRKHFLGRRRRGQPEPEVELNSEGEEVPPDDPPICVSDDNRLCTLASLKAVWHG
  QKLDFFKQAHEGGPAPNSEVVLPDGFQSQHILDYAQGNRPLVLNFGSCTUPPFMARMSAF
  QRLVTKYQRDVDFLIIYIEEAHPSDGWVTTDSPYIIPQHRSLEDRVSAARVLQQGAPGCA
  LVLDTMANSSSSAYGAYFERLYVIQSGTIMYQGGRGPDGYQVSELRTWLERYDEQLHGAR
  PRRV

• Sequence length: 304

Pathways

KEGG:

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROID CANCER, PAPILLARY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Promyelocytic Leukemia	Promyelocytic Leukemia	BEFREE	22522792		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	24317514, 27829231		★☆☆☆☆ Found in Text Mining only
Amaurosis congenita of Leber, type 1	Leber congenital amaurosis	BEFREE	29721936		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	31561084		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	31561084		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	CTD_human_DG	24781735		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Beckwith-Wiedemann Syndrome	Beckwith-Wiedemann Syndrome	BEFREE	31144574		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	30526300		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	CTD_human_DG	25330770		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	29051564		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	29051564, 32807826, 37741974	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cancer of Urinary Tract	Urinary Tract Cancer	BEFREE	30697070		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	21737452, 36482325	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	30526300		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	27829231, 29435111		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	12778072	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	27829231	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	34895303	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	31022560		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	20724312		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	29182613, 31561084		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	28715922		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	31534055		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	30519591	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	31534055		★☆☆☆☆ Found in Text Mining only
Dystonic Disorders	Dystonia	Pubtator	20960437	Associate	★☆☆☆☆ Found in Text Mining only
Familial Nonmedullary Thyroid Cancer	Thyroid cancer	CTD_human_DG	28030816		★☆☆☆☆ Found in Text Mining only
Fatty Liver Alcoholic	Fatty liver, alcoholic	Pubtator	32106257	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	27135827		★☆☆☆☆ Found in Text Mining only
Giant Cell Tumor of Bone	Giant cell tumor of bone	BEFREE	25005035		★☆☆☆☆ Found in Text Mining only
Giant Cell Tumor of Bone	Giant cell tumor of bone	Pubtator	25005035	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	32459347	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	BEFREE	25194663		★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Hematologic neoplasm	Pubtator	19750229	Associate	★☆☆☆☆ Found in Text Mining only
Hemorrhoids	Hemorrhoids	BEFREE	31026569		★☆☆☆☆ Found in Text Mining only
Hepatoblastoma	Hepatoblastoma	Pubtator	32240714	Associate	★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	BEFREE	27066791		★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	BEFREE	21429942, 23554452, 24646062, 28654773		★☆☆☆☆ Found in Text Mining only
Liposarcoma Myxoid	Liposarcoma	Pubtator	25115389	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	21737452		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	27829231	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	BEFREE	30190790		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	CTD_human_DG	25330770		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	29051564		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	21737452		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	27829231, 29435111		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	25324143		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	30526300		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	21737452, 27829231, 30190790		★☆☆☆☆ Found in Text Mining only
Mammary Carcinoma, Human	Marfan Syndrome	CTD_human_DG	25330770		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	CTD_human_DG	25330770		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms, Human	Mammary Neoplasms	CTD_human_DG	25330770		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	29182613, 31561084		★☆☆☆☆ Found in Text Mining only
Metastatic Prostate Carcinoma	Metastatic Prostate Carcinoma	BEFREE	25324143, 26658999		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	15755896, 25886144	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	25886144		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	30743997	Associate	★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	30223454		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	23554452		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	22823995, 23105110, 24646062, 25115389, 26537004, 26825960, 28043921, 29051564, 30190790		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	26188161		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	31468451		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	28715127		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	27135827		★☆☆☆☆ Found in Text Mining only
Nonmedullary Thyroid Carcinoma	Nonmedullary thyroid carcinoma	CTD_human_DG	28030816		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	36320063	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis Knee	Osteoarthritis	Pubtator	22102359	Associate	★☆☆☆☆ Found in Text Mining only
Papillary thyroid carcinoma	Papillary thyroid carcinoma	BEFREE	22823995, 26825960		★☆☆☆☆ Found in Text Mining only
Papillary thyroid carcinoma	Papillary thyroid carcinoma	CTD_human_DG	28030816		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	29483278, 29541577	Associate	★☆☆☆☆ Found in Text Mining only
Prader-Willi Syndrome	Prader-Willi Syndrome	BEFREE	24816254		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	25324143		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	26658999	Associate	★☆☆☆☆ Found in Text Mining only
Recurrent depressive disorder	Mental Depression	BEFREE	27351946		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	21727898		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	21727898		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma of lung	Lung carcinoma	BEFREE	27829231		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	27135827		★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	27329732		★☆☆☆☆ Found in Text Mining only
Uniparental disomy, paternal, chromosome 14	Paternal uniparental disomy of chromosome 14	BEFREE	22917972		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	30526300, 34196584	Associate	★☆☆☆☆ Found in Text Mining only
Vitamin D Deficiency	Vitamin d deficiency	Pubtator	23219444	Associate	★☆☆☆☆ Found in Text Mining only