DIO3 iodothyronine deiodinase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DIO3provided by HGNC
Official Full Name: iodothyronine deiodinase 3provided by HGNC
Primary source: HGNC:HGNC:2885
See related: Ensembl:ENSG00000197406 MIM:601038; AllianceGenome:HGNC:2885
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: D3; 5DIII; TXDI3; DIOIII
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) to inactive metabolites, 3,3',5'-triiodothyronine (RT3) and 3,3'-diiodothyronine (T2), respectively. This enzyme is highly expressed in pregnant uterus, placenta, fetal and neonatal tissues, and thought to prevent premature exposure of developing fetal tissues to adult levels of thyroid hormones. It regulates circulating fetal thyroid hormone concentrations, and thus plays a critical role in mammalian development. Knockout mice lacking this gene exhibit abnormalities related to development and reproduction, and increased activity of this enzyme in infants with hemangiomas causes severe hypothyroidism. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. [provided by RefSeq, May 2016]
Orthologs: mouse all
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Genomic context

Location:: 14q32.31

Exon count:: 1

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (101561495..101563452)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (95796749..95798706)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (102027688..102029789)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Evaluating the link between DIO3-FA27 promoter methylation, biochemical indices, and heart failure progression.
Title: Evaluating the link between DIO3-FA27 promoter methylation, biochemical indices, and heart failure progression.
MiRNAs from the Dlk1-Dio3 locus and miR-224/452 cluster contribute to glioblastoma tumor heterogeneity.
Title: MiRNAs from the Dlk1-Dio3 locus and miR-224/452 cluster contribute to glioblastoma tumor heterogeneity.
DLK1/DIO3 locus upregulation by a beta-catenin-dependent enhancer drives cell proliferation and liver tumorigenesis.
Title: DLK1/DIO3 locus upregulation by a β-catenin-dependent enhancer drives cell proliferation and liver tumorigenesis.
Effect of epigenetic activating of Dlk1-Dio3 imprinted cluster on miR-370 expression due to folate deficiency during nerve development.
Title: Effect of epigenetic activating of Dlk1-Dio3 imprinted cluster on miR-370 expression due to folate deficiency during nerve development.
MiR-24-3p/Dio3 axis is essential for BDE47 to induce local thyroid hormone disorder and neurotoxicity.
Title: MiR-24-3p/Dio3 axis is essential for BDE47 to induce local thyroid hormone disorder and neurotoxicity.
Loss of Selenoprotein Iodothyronine Deiodinase 3 Expression Correlates with Progression of Complete Hydatidiform Mole to Gestational Trophoblastic Neoplasia.
Title: Loss of Selenoprotein Iodothyronine Deiodinase 3 Expression Correlates with Progression of Complete Hydatidiform Mole to Gestational Trophoblastic Neoplasia.
Downregulation of Caveolin-1 and Upregulation of Deiodinase 3, Associated with Hypoxia-Inducible Factor-1alpha Increase, Are Involved in the Oxidative Stress of Graves' Orbital Adipocytes.
Title: Downregulation of Caveolin-1 and Upregulation of Deiodinase 3, Associated with Hypoxia-Inducible Factor-1α Increase, Are Involved in the Oxidative Stress of Graves' Orbital Adipocytes.
Human placental piwi-interacting RNA transcriptome is characterized by expression from the DLK1-DIO3 imprinted region.
Title: Human placental piwi-interacting RNA transcriptome is characterized by expression from the DLK1-DIO3 imprinted region.
Deiodinases and the Metabolic Code for Thyroid Hormone Action.
Title: Deiodinases and the Metabolic Code for Thyroid Hormone Action.
DIO3, the thyroid hormone inactivating enzyme, promotes tumorigenesis and metabolic reprogramming in high grade serous ovarian cancer.
Title: DIO3, the thyroid hormone inactivating enzyme, promotes tumorigenesis and metabolic reprogramming in high grade serous ovarian cancer.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH103871 (e-PCR)
- UniSTS:98196

STS-S79854 (e-PCR)
- UniSTS:34780

MARC_54596-54595:1155067325:1 (e-PCR)
- UniSTS:508155

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables thyroxine 5'-deiodinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables thyroxine 5'-deiodinase activity	NAS Non-traceable Author Statement more info	PubMed
enables thyroxine 5'-deiodinase activity	TAS Traceable Author Statement more info
enables thyroxine 5-deiodinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in brown fat cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in hormone biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in retinal cone cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in retinal cone cell development	IEA Inferred from Electronic Annotation more info
involved_in thyroid hormone catabolic process	IEA Inferred from Electronic Annotation more info
involved_in thyroid hormone metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in thyroid hormone metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in thyroid hormone metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: thyroxine 5-deiodinase

Names: deiodinase, iodothyronine type III; iodothyronine deiodinase, placental type; selenoprotein DIO3; thyroxine deiodinase type III (selenoprotein); type 3 DI; type 3 iodothyronine selenodeiodinase; type-III 5' deiodinase

NP_001353.4

EC 1.21.99.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.