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DIO1 iodothyronine deiodinase 1 [ Homo sapiens (human) ]

Gene ID: 1733, updated on 5-Mar-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (53894187..53911086)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (53777070..53793996)
105.20220307 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
  • 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. [Association between DIO polymorphism and aerobic endurance]. Zhou WT, et al. Zhongguo Ying Yong Sheng Li Xue Za Zhi, 2019 Feb. PMID 31250614
  2. The relationship between inflammatory factors, oxidative stress and DIO-1 concentration in patients with chronic renal failure accompanied with or without euthyroid sick syndrome. Qin SL, et al. J Int Med Res, 2018 Oct. PMID 30152254, Free PMC Article
  3. Investigation of the Oxidative Stress and DIO1 Expression in CRF Patients Accompanied With and Without Euthyroid Sick Syndrome. Shu-Lan Q, et al. Kidney Blood Press Res, 2018. PMID 29894998
  4. Restoration of type 1 iodothyronine deiodinase expression in renal cancer cells downregulates oncoproteins and affects key metabolic pathways as well as anti-oxidative system. Popławski P, et al. PLoS One, 2017. PMID 29272308, Free PMC Article
  5. The relationship of 19 functional polymorphisms in iodothyronine deiodinase and psychological well-being in hypothyroid patients. Young Cho Y, et al. Endocrine, 2017 Jul. PMID 28466400

See all (70) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. polymorphisms in DIO1 are associated with aerobic endurance performance
    Title: [Association between DIO polymorphism and aerobic endurance].
  9. 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.
  10. Multivariate linear regression analysis revealed that the DIO1 concentration and FT3 level were not associated with the concentration of serum 8-Isoprostane
    Title: Investigation of the Oxidative Stress and DIO1 Expression in CRF Patients Accompanied With and Without Euthyroid Sick Syndrome.
Submit: New GeneRIF Correction See all GeneRIFs (46)

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)

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

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_2023_10

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

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