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    DIO1 iodothyronine deiodinase 1 [ Homo sapiens (human) ]

    Gene ID: 1733, updated on 2-Nov-2024

    Summary

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    Official Symbol
    DIO1provided by HGNC
    Official Full Name
    iodothyronine deiodinase 1provided by HGNC
    Primary source
    HGNC:HGNC:2883
    See related
    Ensembl:ENSG00000211452 MIM:147892; AllianceGenome:HGNC:2883
    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
    5DI; THMA2; TXDI1
    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 conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination. This protein provides most of the circulating T3, which is essential for growth, differentiation and basal metabolism in vertebrates. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2018]
    Expression
    Biased expression in thyroid (RPKM 180.4), kidney (RPKM 58.4) and 1 other tissue See more
    Orthologs
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    Genomic context

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    See DIO1 in Genome Data Viewer
    Location:
    1p32.3
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (53894187..53911086)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (53777070..53793996)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (54359860..54376759)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein L37 pseudogene 7 Neighboring gene Yip1 domain family member 1 Neighboring gene Sharpr-MPRA regulatory region 6831 Neighboring gene Sharpr-MPRA regulatory region 3939 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:54359446-54359946 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:54359947-54360447 Neighboring gene uncharacterized LOC124904180 Neighboring gene uncharacterized LOC124904181 Neighboring gene intraflagellar transport 25 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 913 Neighboring gene Sharpr-MPRA regulatory region 3629 Neighboring gene leucine rich repeat containing 42 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:54422389-54423588 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:54424449-54425155

    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. The effect of the D1-C785T polymorphism in the type 1 iodothyronine deiodinase gene on the circulating thyroid hormone levels in Romanian women with preeclampsia. Association with the degree of severity and pregnancy outcome of preeclampsia. Procopciuc LM, et al. Gynecol Endocrinol, 2012 May. PMID 22339181
    2. Polymorphisms of iodothyronine deiodinases (DIO1, DIO3) genes are not associated with recurrent depressive disorder. Gałecka E, et al. Pharmacol Rep, 2016 Oct. PMID 27351946
    3. Polymorphisms in the type I deiodinase gene and frontal function in recurrent depressive disorder. Gałecka E, et al. Adv Med Sci, 2016 Sep. PMID 26866568
    4. The promoter of the human type I 5'-deiodinase gene--mapping of the transcription start site and identification of a DR+4 thyroid-hormone-responsive element. Jakobs TC, et al. Eur J Biochem, 1997 Jul 1. PMID 9249039
    5. Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves' disease. Nishikawa M, et al. Biochem Biophys Res Commun, 1998 Sep 29. PMID 9784399

    See all (73) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer.
      Title: The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer.
    2. A regulatory element associated to NAFLD in the promoter of DIO1 controls LDL-C, HDL-C and triglycerides in hepatic cells.
      Title: A regulatory element associated to NAFLD in the promoter of DIO1 controls LDL-C, HDL-C and triglycerides in hepatic cells.
    3. SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.
      Title: SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.
    4. 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.
    5. Novel DIO1 Gene Mutation Acting as Phenotype Modifier for Novel Compound Heterozygous TPO Gene Mutations Causing Congenital Hypothyroidism.
      Title: Novel DIO1 Gene Mutation Acting as Phenotype Modifier for Novel Compound Heterozygous TPO Gene Mutations Causing Congenital Hypothyroidism.
    6. Human Type 1 Iodothyronine Deiodinase (DIO1) Mutations Cause Abnormal Thyroid Hormone Metabolism.
      Title: Human Type 1 Iodothyronine Deiodinase (DIO1) Mutations Cause Abnormal Thyroid Hormone Metabolism.
    7. Deiodinases, organic anion transporter polypeptide polymorphisms and symptoms of anxiety and depression after ischemic stroke.
      Title: Deiodinases, organic anion transporter polypeptide polymorphisms and symptoms of anxiety and depression after ischemic stroke.
    8. Our results indicate that increased thyroidal D1 and D2 activities may be responsible for the higher serum FT3/FT4 ratio in patients with huge goitrous Hashimoto's thyroiditis.
      Title: Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with huge goitrous Hashimoto's thyroiditis.
    9. polymorphisms in DIO1 are associated with aerobic endurance performance
      Title: [Association between DIO polymorphism and aerobic endurance].
    10. this current study found that the serum DIO-1 concentration was inversely correlated with the concentration of TNF-alpha, which suggests that DIO-1 might inhibit the production of serum TNF-alpha in patients with chronic renal failure
      Title: The relationship between inflammatory factors, oxidative stress and DIO-1 concentration in patients with chronic renal failure accompanied with or without euthyroid sick syndrome.
    Submit: New GeneRIF Correction See all GeneRIFs (47)

    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

    Associated conditions

    Description Tests
    Thyroid hormone metabolism, abnormal, 2
    MedGen: C5676976 OMIM: 619855 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.
    EBI GWAS Catalog
    The CCND1 c.870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Clone Names

    • MGC130050, MGC130051

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables selenium binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables thyroxine 5'-deiodinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in amino acid metabolic process IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in hormone biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    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
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    type I iodothyronine deiodinase
    Names
    DIOI
    deiodinase, iodothyronine type I
    iodothyronine deiodinase type 1
    selenoprotein DIO1
    thyroxine 5'-deiodinase
    thyroxine deiodinase type I (selenoprotein)
    type 1 DI
    type-I 5'-deiodinase
    NP_000783.2
    NP_001034804.1
    NP_001034805.1
    NP_001311245.1
    NP_998758.1

    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.

    Genomic

    1. NG_023306.1 RefSeqGene

      Range
      5000..21899
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000792.7 → NP_000783.2  type I iodothyronine deiodinase isoform a

      See identical proteins and their annotated locations for NP_000783.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AK290780, BC017955, BE046205
      Consensus CDS
      CCDS41339.1
      UniProtKB/Swiss-Prot
      P49895, Q1RN02, Q3KNP8, Q6Q4C1, Q6Q4C2, Q6Q4C3, Q6Q4C4, Q6Q4C5, Q6Q4C6, Q6Q4C7, Q6Q4C9, Q8WWC6
      Related
      ENSP00000354643.4, ENST00000361921.8
      Conserved Domains (1) summary
      cl00388
      Location:8 → 248
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    2. NM_001039715.3 → NP_001034804.1  type I iodothyronine deiodinase isoform c

      See identical proteins and their annotated locations for NP_001034804.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame exon in the coding region compared to variant 1. The resulting isoform (c) is shorter, lacking an internal selenocysteine-containing protein segment compared to isoform a.
      Source sequence(s)
      AK290780, AY560377, BC017955, BE046205
      Consensus CDS
      CCDS30722.1
      UniProtKB/Swiss-Prot
      P49895
      UniProtKB/TrEMBL
      A8K415
      Related
      ENSP00000373528.3, ENST00000388876.3
      Conserved Domains (1) summary
      cl00388
      Location:8 → 200
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    3. NM_001039716.3 → NP_001034805.1  type I iodothyronine deiodinase isoform d

      See identical proteins and their annotated locations for NP_001034805.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an exon in the 3' coding region, which causes a frameshift compared to variant 1. The resulting isoform (d) is shorter, with a distinct C-terminus compared to isoform a.
      Source sequence(s)
      AK290780, BC017955, BE046205
      Consensus CDS
      CCDS41340.1
      UniProtKB/Swiss-Prot
      P49895
      UniProtKB/TrEMBL
      A8K415
      Related
      ENSP00000323198.6, ENST00000322679.10
      Conserved Domains (1) summary
      cl00388
      Location:8 → 160
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    4. NM_001324316.2 → NP_001311245.1  type I iodothyronine deiodinase isoform e

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks two internal exons, which causes a frameshift compared to variant 1. The resulting shorter isoform (e) has the same N-terminus but a distinct C-terminus compared to isoform a.
      Source sequence(s)
      AK290780, AY560381, BC017955, BE046205
      Consensus CDS
      CCDS81328.1
      UniProtKB/TrEMBL
      C6ZRC2
      Related
      ENSP00000434758.1, ENST00000532493.5
      Conserved Domains (1) summary
      cl00388
      Location:8 → 113
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    5. NM_213593.5 → NP_998758.1  type I iodothyronine deiodinase isoform b

      See identical proteins and their annotated locations for NP_998758.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame donor splice site at the 5' terminal exon compared to variant 1. The resulting isoform (b) is shorter, lacking a 64 aa protein segment in the 5' coding region compared to isoform a.
      Source sequence(s)
      AK290780, AY560375, BC017955, BE046205
      Consensus CDS
      CCDS53320.1
      UniProtKB/Swiss-Prot
      P49895
      UniProtKB/TrEMBL
      A8K415
      Related
      ENSP00000435725.1, ENST00000525202.5
      Conserved Domains (1) summary
      cl00388
      Location:8 → 184
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    RNA

    1. NR_136692.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate donor splice site at the 5' terminal exon compared to variant 1. It 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)
      AK290780, AY560379, BC017955, BE046205

    2. NR_136693.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) is alternatively spliced at the 5' end compared to variant 1. It 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)
      AK290780, AY560382, BC017955, BE046205

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      53894187..53911086
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      53777070..53793996
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49895.3 GenPept UniProtKB/Swiss-Prot:P49895

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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