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    DIO2 iodothyronine deiodinase 2 [ Homo sapiens (human) ]

    Gene ID: 1734, updated on 28-Oct-2024

    Summary

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    Official Symbol
    DIO2provided by HGNC
    Official Full Name
    iodothyronine deiodinase 2provided by HGNC
    Primary source
    HGNC:HGNC:2884
    See related
    Ensembl:ENSG00000211448 MIM:601413; AllianceGenome:HGNC:2884
    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
    D2; 5DII; SelY; DIOII; TXDI2; SELENOY
    Summary
    The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the conversion of prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4) to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by outer ring 5'-deiodination. This gene is widely expressed, including in thyroid and brain. It is thought to be responsible for the 'local' production of T3, and thus important in influencing thyroid hormone action in these tissues. It has also been reported to be highly expressed in thyroids of patients with Graves disease, and in follicular adenomas. The intrathyroidal T4 to T3 conversion by this enzyme may contribute significantly to the relative increase in thyroidal T3 production in these patients. This protein is a selenoprotein containing the non-standard amino acid, selenocysteine (Sec), which is encoded by the UGA codon that 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. Unlike the other two members (DIO1 and DIO3) of this enzyme family, the mRNA for this gene contains an additional in-frame UGA codon that has been reported (in human) to function either as a Sec or a stop codon, which can result in two isoforms with one or two Sec residues; however, only the upstream Sec (conserved with the single Sec residue found at the active site in DIO1 and DIO3) was shown to be essential for enzyme activity (PMID:10403186). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2018]
    Expression
    Biased expression in thyroid (RPKM 69.7), endometrium (RPKM 13.6) and 2 other tissues See more
    Orthologs
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    Genomic context

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    See DIO2 in Genome Data Viewer
    Location:
    14q31.1
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (80197526..80231057, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (74407785..74441322, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (80663869..80697400, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370591 Neighboring gene uncharacterized LOC105370593 Neighboring gene DIO2 antisense RNA 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:80930624-80931315 Neighboring gene centrosomal protein 128 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_37660 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_37671 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_37742 Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8818 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8819 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8820 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8821 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8822 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:81439163-81439664 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:81439665-81440164 Neighboring gene GPRASP3 pseudogene 1 Neighboring gene thyroid stimulating hormone receptor

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. Maia AL, et al. J Clin Invest, 2005 Sep. PMID 16127464, Free PMC Article
    2. Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3'-triiodothyronine therapy. Appelhof BC, et al. J Clin Endocrinol Metab, 2005 Nov. PMID 16144953
    3. Association analyses of variants in the DIO2 gene with early-onset type 2 diabetes mellitus in Pima Indians. Nair S, et al. Thyroid, 2012 Jan. PMID 22142372, Free PMC Article
    4. Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells. Kasahara T, et al. Atherosclerosis, 2006 May. PMID 16140305
    5. Deiodinase 2 expression is increased in dorsocervical fat of patients with HIV-associated lipohypertrophy syndrome. Torriani M, et al. J Clin Endocrinol Metab, 2012 Apr. PMID 22259052, Free PMC Article

    See all (152) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Thr92Ala-DIO2 heterozygosity is associated with skeletal muscle mass and myosteatosis in patients with COVID-19.
      Title: Thr92Ala-DIO2 heterozygosity is associated with skeletal muscle mass and myosteatosis in patients with COVID-19.
    2. The Thr92Ala polymorphism in the type 2 deiodinase gene is linked to depression in patients with COVID-19 after hospital discharge.
      Title: The Thr92Ala polymorphism in the type 2 deiodinase gene is linked to depression in patients with COVID-19 after hospital discharge.
    3. Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population.
      Title: Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population.
    4. Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank.
      Title: Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank.
    5. Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers.
      Title: Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers.
    6. Association between DIO2 Thr92Ala polymorphism and hypertension in patients with hypothyroidism: Korean Genome and Epidemiology Study.
      Title: Association between DIO2 Thr92Ala polymorphism and hypertension in patients with hypothyroidism: Korean Genome and Epidemiology Study.
    7. Single-cell profiling of the microenvironment in decidual tissue from women with missed abortions.
      Title: Single-cell profiling of the microenvironment in decidual tissue from women with missed abortions.
    8. Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes.
      Title: Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes.
    9. Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery.
      Title: Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery.
    10. Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease.
      Title: Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease.
    Submit: New GeneRIF Correction See all GeneRIFs (124)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables selenium binding IC
    Inferred by Curator
    more info
    		 PubMed 
    enables thyroxine 5'-deiodinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables thyroxine 5'-deiodinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables thyroxine 5'-deiodinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables thyroxine 5-deiodinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in hormone biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cold-induced thermogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in selenocysteine incorporation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in thyroid hormone generation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in thyroid hormone metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in thyroid hormone metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in membrane IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    type II iodothyronine deiodinase
    Names
    deiodinase, iodothyronine type II
    deiodinase-2
    deiodonase-2
    selenoprotein Y
    thyroxine deiodinase, type II
    type 2 DI
    type 2 iodothyronine deiodinase
    type-II 5'-deiodinase
    type-II 5'deiodinase
    NP_000784.3
    NP_001311391.2
    NP_001353425.1
    NP_054644.1

    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.

    mRNA and Protein(s)

    1. NM_000793.6 → NP_000784.3  type II iodothyronine deiodinase isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses a different promoter and contains two novel 5' non-coding exons; thus, has a longer 5' UTR compared to the variant 1. Variants 1 (NM_001366496.1), 2 and 3 represent the same one-Sec containing isoform (b), considered to be the canonical form.
      Source sequence(s)
      AC007372, AF093774, AK292210, BC136514
      Related
      ENSP00000451419.1, ENST00000557010.5

    2. NM_001324462.2 → NP_001311391.2  type II iodothyronine deiodinase isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses a different promoter and contains a novel 5' non-coding exon; thus, has a longer 5' UTR compared to variant 1. Variants 1 (NM_001366496.1), 2 and 3 represent the same one-Sec containing isoform (b), considered to be the canonical form.
      Source sequence(s)
      AC007372, AF093774, BC136514, CD701270, JK546617

    3. NM_001366496.1 → NP_001353425.1  type II iodothyronine deiodinase isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as hDII-a) represents the predominant transcript and encodes two isoforms resulting from the use of alternative in-frame translation termination codons. The shorter isoform (b) with one Sec residue results from translation termination at the second UGA codon, while the longer isoform (a) with two Sec residues results from translation termination at an in-frame downstream UAA stop codon. This RefSeq represents the shorter isoform (b), which is considered the canonical form as the protein extension past the second UGA codon is not conserved in orthologs from other vertebrate species. Variants 2 and 3 also represent isoform b.
      Source sequence(s)
      AC007372, AF093774, BC136514

    4. NM_013989.5 → NP_054644.1  type II iodothyronine deiodinase isoform a

      See identical proteins and their annotated locations for NP_054644.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as hDII-a) represents the predominant transcript and encodes two isoforms resulting from the use of alternative in-frame translation termination codons. The shorter isoform (b) with one Sec residue results from translation termination at the second UGA codon, while the longer isoform (a) with two Sec residues results from translation termination at an in-frame downstream UAA stop codon. This RefSeq represents the longer isoform (a).
      Source sequence(s)
      AC007372, AF093774, BC136514
      Consensus CDS
      CCDS45146.1
      UniProtKB/Swiss-Prot
      B9EGK0, G3V315, Q6B0A3, Q92813, Q9HCP7, Q9HCP8, Q9P1W4, Q9UDZ1
      Related
      ENSP00000405854.5, ENST00000438257.9
      Conserved Domains (1) summary
      pfam00837
      Location:4 → 262
      T4_deiodinase; Iodothyronine deiodinase

    RNA

    1. NR_158990.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4, also known as hDII-b) contains an internal novel exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most translational start codon, as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AB041843, AC007372, AF093774, BC136514

    2. NR_158991.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5, also known as hDII-c) contains two internal novel exons compared to variant 1. This variant is represented as non-coding because the use of the 5'-most translational start codon, as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AB041844, AC007372, AF093774, BC136514

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      80197526..80231057 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      74407785..74441322 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001007023.4: Suppressed sequence

      Description
      NM_001007023.4: This RefSeq was removed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    2. NM_001242503.2: Suppressed sequence

      Description
      NM_001242503.2: This RefSeq was removed because currently there is partial support for the transcript but none for the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92813.4 GenPept UniProtKB/Swiss-Prot:Q92813

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