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Aliases for DIO2 Gene

Aliases for DIO2 Gene

  • Deiodinase, Iodothyronine, Type II 2 3 5
  • Type-II 5-Deiodinase 3 4
  • Deiodonase-2 2 3
  • Deiodinase-2 2 3
  • Type 2 DI 3 4
  • DIOII 3 4
  • TXDI2 3 4
  • 5DII 3 4
  • Type 2 Iodothyronine Deiodinase 3
  • Thyroxine Deiodinase, Type II 3
  • Thyroxine Deiodinase 2
  • Type-II 5deiodinase 3
  • EC 63
  • EC 4
  • EC 1.97.1 63
  • Type II 2
  • ITDI2 4
  • SelY 3
  • D2 3

External Ids for DIO2 Gene

Previous GeneCards Identifiers for DIO2 Gene

  • GC14M078169
  • GC14M074480
  • GC14M078653
  • GC14M079733
  • GC14M080663
  • GC14M060829

Summaries for DIO2 Gene

Entrez Gene Summary for DIO2 Gene

  • The protein encoded by this gene belongs to the iodothyronine deiodinase family. It activates thyroid hormone by converting the prohormone thyroxine (T4) by outer ring deiodination (ORD) to bioactive 3,3',5-triiodothyronine (T3). It is highly expressed in the thyroid, and may contribute significantly to the relative increase in thyroidal T3 production in patients with Graves disease and thyroid adenomas. This protein contains selenocysteine (Sec) residues encoded by the UGA codon, which normally signals translation termination. The 3' UTR of Sec-containing genes have a common stem-loop structure, the sec insertion sequence (SECIS), which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneCards Summary for DIO2 Gene

DIO2 (Deiodinase, Iodothyronine, Type II) is a Protein Coding gene. Diseases associated with DIO2 include Graves' Disease and Euthyroid Sick Syndrome. Among its related pathways are Thyroid hormone signaling pathway and Amine-derived hormones. GO annotations related to this gene include oxidoreductase activity and antioxidant activity. An important paralog of this gene is DIO3.

UniProtKB/Swiss-Prot for DIO2 Gene

  • Responsible for the deiodination of T4 (3,5,3,5-tetraiodothyronine) into T3 (3,5,3-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.

Gene Wiki entry for DIO2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DIO2 Gene

Genomics for DIO2 Gene

Regulatory Elements for DIO2 Gene

Enhancers for DIO2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around DIO2 on UCSC Golden Path with GeneCards custom track

Genomic Location for DIO2 Gene

80,197,525 bp from pter
80,387,757 bp from pter
190,233 bases
Minus strand

Genomic View for DIO2 Gene

Genes around DIO2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DIO2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DIO2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DIO2 Gene

Proteins for DIO2 Gene

  • Protein details for DIO2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Type II iodothyronine deiodinase
    Protein Accession:
    Secondary Accessions:
    • B9EGK0
    • G3V315
    • Q6B0A3
    • Q9HCP8
    • Q9P1W4
    • Q9UDZ1

    Protein attributes for DIO2 Gene

    273 amino acids
    Molecular mass:
    30552 Da
    Quaternary structure:
    • Interacts with USP20 and USP33. Interacts with MARCH6.
    • Sequence=AAC95470.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for DIO2 Gene


neXtProt entry for DIO2 Gene

Proteomics data for DIO2 Gene at MOPED

Post-translational modifications for DIO2 Gene

  • Ubiquitinated by MARCH6, leading to its degradation by the proteasome. Deubiquitinated by USP20 and USP33.

Domains & Families for DIO2 Gene

Suggested Antigen Peptide Sequences for DIO2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the iodothyronine deiodinase family.
  • Belongs to the iodothyronine deiodinase family.
genes like me logo Genes that share domains with DIO2: view

No data available for Gene Families for DIO2 Gene

Function for DIO2 Gene

Molecular function for DIO2 Gene

GENATLAS Biochemistry:
iodothyronine 5-deiodinase type II,selenocysteine containing,expressed in thyroid,involved in the regulation of local T4 to T3 conversion
UniProtKB/Swiss-Prot CatalyticActivity:
3,5,3-triiodo-L-thyronine + iodide + A + H(+) = L-thyroxine + AH(2).
UniProtKB/Swiss-Prot Function:
Responsible for the deiodination of T4 (3,5,3,5-tetraiodothyronine) into T3 (3,5,3-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.

Enzyme Numbers (IUBMB) for DIO2 Gene

genes like me logo Genes that share phenotypes with DIO2: view

Animal Models for DIO2 Gene

MGI Knock Outs for DIO2:

Animal Model Products

No data available for Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DIO2 Gene

Localization for DIO2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DIO2 Gene

Membrane; Single-pass membrane protein.

Subcellular locations from

Jensen Localization Image for DIO2 Gene COMPARTMENTS Subcellular localization image for DIO2 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 2
extracellular 2
nucleus 2
cytoskeleton 1
mitochondrion 1
peroxisome 1

No data available for Gene Ontology (GO) - Cellular Components for DIO2 Gene

Pathways & Interactions for DIO2 Gene

genes like me logo Genes that share pathways with DIO2: view

Gene Ontology (GO) - Biological Process for DIO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006590 thyroid hormone generation TAS 9837913
GO:0034641 cellular nitrogen compound metabolic process TAS --
GO:0042403 thyroid hormone metabolic process IDA 19651899
GO:0044281 small molecule metabolic process TAS --
genes like me logo Genes that share ontologies with DIO2: view

No data available for SIGNOR curated interactions for DIO2 Gene

Drugs & Compounds for DIO2 Gene

(20) Drugs for DIO2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Levothyroxine Approved Pharma 0
Liothyronine Approved Pharma 0
Selenocysteine Experimental Pharma 0
Selenium Pharma 168

(16) Additional Compounds for DIO2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
  • Iodide
  • Iodide anion
  • Iodide ion
  • Iodide Salt
  • Iodide(1-)
Thyroxine sulfate
  • 3,5,3',5'-Tetraiodo-L-thyronine 4'-O-sulfate
  • 3,5,3',5'-Tetraiodo-L-thyronine 4'-O-sulphate
  • 3,5,3',5'-Tetraiodo-L-thyronine 4-O-sulfate
  • 3,5,3',5'-Tetraiodo-L-thyronine 4-O-sulphate
  • 3-[4-(4-Hydroxy-3,5-diiodophenoxy-4-O-sulfate)-3,5-diiodophenyl]-L-alanine
genes like me logo Genes that share compounds with DIO2: view

Transcripts for DIO2 Gene

Unigene Clusters for DIO2 Gene

Deiodinase, iodothyronine, type II:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for DIO2 Gene

No ASD Table

Relevant External Links for DIO2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for DIO2 Gene

mRNA expression in normal human tissues for DIO2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DIO2 Gene

This gene is overexpressed in Esophagus - Mucosa (x7.4) and Thyroid (x7.0).

SOURCE GeneReport for Unigene cluster for DIO2 Gene Hs.202354

mRNA Expression by UniProt/SwissProt for DIO2 Gene

Tissue specificity: Heart, skeletal muscle, placenta, fetal brain and several regions of the adult brain.
genes like me logo Genes that share expression patterns with DIO2: view

Primer Products

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for DIO2 Gene

Orthologs for DIO2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for DIO2 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia DIO2 35
  • 92.13 (n)
  • 92.51 (a)
DIO2 36
  • 86 (a)
(Canis familiaris)
Mammalia DIO2 35
  • 93.58 (n)
  • 93.58 (a)
DIO2 36
  • 92 (a)
(Mus musculus)
Mammalia Dio2 35
  • 88.68 (n)
  • 91.22 (a)
Dio2 16
Dio2 36
  • 89 (a)
(Pan troglodytes)
Mammalia DIO2 35
  • 99.68 (n)
  • 99.35 (a)
(Rattus norvegicus)
Mammalia Dio2 35
  • 88.04 (n)
  • 90.84 (a)
(Monodelphis domestica)
Mammalia DIO2 36
  • 67 (a)
(Ornithorhynchus anatinus)
Mammalia DIO2 36
  • 80 (a)
(Gallus gallus)
Aves DIO2 35
  • 77.27 (n)
  • 83.33 (a)
DIO2 36
  • 69 (a)
(Anolis carolinensis)
Reptilia DIO2 36
  • 91 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia dio2 35
  • 73.57 (n)
  • 78.52 (a)
African clawed frog
(Xenopus laevis)
Amphibia dio2-A 35
(Danio rerio)
Actinopterygii dio2 35
  • 70.82 (n)
  • 71.21 (a)
dio2 36
  • 70 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.163 35
Species with no ortholog for DIO2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for DIO2 Gene

Gene Tree for DIO2 (if available)
Gene Tree for DIO2 (if available)

Paralogs for DIO2 Gene

Paralogs for DIO2 Gene

(2) SIMAP similar genes for DIO2 Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with DIO2: view

Variants for DIO2 Gene

Sequence variations from dbSNP and Humsavar for DIO2 Gene

SNP ID Clin Chr 14 pos Sequence Context AA Info Type
rs225014 - 80,203,237(+) TTCTG(C/T)ACTGG reference, missense, utr-variant-3-prime
rs2839859 - 80,203,269(-) GGATG(A/C)CCCCA reference, missense, utr-variant-3-prime
rs172801 -- 80,198,592(+) CTTTT(C/T)TTAGA utr-variant-3-prime
rs184416 -- 80,198,662(-) TTCCA(A/G)AATGG utr-variant-3-prime
rs225010 -- 80,205,936(+) GGTGA(C/T)GGATA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for DIO2 Gene

Variant ID Type Subtype PubMed ID
nsv902113 CNV Gain 21882294
esv25191 CNV Gain 19812545

Variation tolerance for DIO2 Gene

Residual Variation Intolerance Score: 45.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.80; 47.54% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for DIO2 Gene

Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DIO2 Gene

Disorders for DIO2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for DIO2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
graves' disease
  • toxic diffuse goiter
euthyroid sick syndrome
  • sick-euthyroid syndrome
kashin-beck disease
thyroid cancer, nonmedullary, 2
  • thyroid carcinoma, follicular, somatic
thyroid gland disease
  • thyroid diseases
- elite association - COSMIC cancer census association via MalaCards
Search DIO2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for DIO2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with DIO2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DIO2 Gene

Publications for DIO2 Gene

  1. Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. (PMID: 8755651) Croteau W. … St Germain D.L. (J. Clin. Invest. 1996) 2 3 4 67
  2. Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway. (PMID: 20176747) Christoffolete M.A. … Gereben B. (J. Endocrinol. 2010) 3 23
  3. The type 2 deiodinase Thr92Ala polymorphism is associated with increased bone turnover and decreased femoral neck bone mineral density. (PMID: 20200941) Heemstra K.A. … Smit J.W. (J. Bone Miner. Res. 2010) 3 23
  4. Regional decrease of subcutaneous adipose tissue in patients with type 2 familial partial lipodystrophy is associated with changes in thyroid hormone metabolism. (PMID: 20373986) Lado-Abeal J. … Araujo-Vilar D. (Thyroid 2010) 3 23
  5. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. (PMID: 19190113) Panicker V. … Dayan C.M. (J. Clin. Endocrinol. Metab. 2009) 3 23

Products for DIO2 Gene

Sources for DIO2 Gene