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DIO3 Gene(Protein Coding)

Iodothyronine Deiodinase 3

GCID:
GC14P103275
GIFtS:
44
Genes Participants
UDN Logo

Aliases for DIO3 Gene

Aliases for DIO3 Gene

  • Iodothyronine Deiodinase 3 2 3 5
  • Deiodinase, Iodothyronine Type III 2 3
  • Thyroxine 5-Deiodinase 2 3
  • Type 3 DI 3 4
  • DIOIII 3 4
  • TXDI3 3 4
  • 5DIII 3 4
  • Thyroxine Deiodinase Type III (Selenoprotein) 3
  • Iodothyronine Deiodinase, Placental Type 3
  • Type 3 Iodothyronine Selenodeiodinase 3
  • Type III Iodothyronine Deiodinase 4
  • Type-III 5 Deiodinase 3
  • EC 1.21.99.3 4
  • ITDI3 4
  • D3 3

External Ids for DIO3 Gene

Previous HGNC Symbols for DIO3 Gene

  • TXDI3

Previous GeneCards Identifiers for DIO3 Gene

  • GC14P099418
  • GC14P095843
  • GC14P100017
  • GC14P101097
  • GC14P102027
  • GC14P082210
  • GC14P101881
  • GC14P101905
  • GC14P102216
  • GC14P102383
  • GC14P102561
  • GC14P102733
  • GC14P102903
  • GC14P103079

Summaries for DIO3 Gene

Entrez Gene Summary for DIO3 Gene

  • 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]

GeneCards Summary for DIO3 Gene

DIO3 (Iodothyronine Deiodinase 3) is a Protein Coding gene. Diseases associated with DIO3 include Hypothyroidism and Neonatal Thyrotoxicosis. Among its related pathways are Metabolism and Thyroid hormone signaling pathway. Gene Ontology (GO) annotations related to this gene include thyroxine 5-deiodinase activity and thyroxine 5-deiodinase activity. An important paralog of this gene is DIO2.

UniProtKB/Swiss-Prot for DIO3 Gene

  • Responsible for the deiodination of T4 (3,5,3,5-tetraiodothyronine) into RT3 (3,3,5-triiodothyronine) and of T3 (3,5,3-triiodothyronine) into T2 (3,3-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development.

Additional gene information for DIO3 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DIO3 Gene

Genomics for DIO3 Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for DIO3 Gene

Promoters and enhancers for DIO3 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH14J101561 Enhancer 0.6 ENCODE 650.7 +0.0 38 0.2 SP3 L3MBTL2 SP2 ZBTB8A GLIS2 ZFHX2 ZBTB48 POLR2A SETDB1 GC14P103339 MIR1247 DIO3OS DIO3 GC14P103476
GH14J101559 Enhancer 0.5 ENCODE 650.7 -1.4 -1441 1.8 ZNF335 CTCF SUZ12 NFATC1 ZSCAN4 RAD21 EZH2 DIO3 DIO3OS MIR1247 LOC105370674 GC14P103476
GH14J100616 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 12 -943.4 -943374 2 PKNOX1 ELF1 RARA GABPA NFIL3 GATA3 ZNF366 ZBTB48 GABPB1 CUX1 BEGAIN DIO3 DIO3OS DLK1 ENSG00000258576 PIR56329
GH14J100769 Enhancer 1.4 FANTOM5 ENCODE dbSUPER 9.7 -785.7 -785733 12.7 HDGF PKNOX1 SMAD1 ATF1 FOXA2 ARNT ZNF48 NCOA2 TCF12 ZNF766 DLK1 MIR1247 DIO3 EVL MEG3 PIR41786
GH14J101628 Enhancer 1.1 Ensembl ENCODE 10.7 +67.3 67271 1.2 RB1 SIN3A ZNF2 THRB ZNF48 RAD21 RARA ZNF335 ARID2 ZNF143 DIO3 MIR1247 ENSG00000258919 LOC105370675 LINC02320
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DIO3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the DIO3 gene promoter:
  • Nkx3-1 v4
  • Nkx3-1 v3
  • Nkx3-1 v2
  • Nkx3-1 v1
  • Nkx3-1
  • GR-alpha
  • GR
  • PPAR-alpha
  • STAT5A

Genomic Locations for DIO3 Gene

Genomic Locations for DIO3 Gene
chr14:101,561,351-101,563,452
(GRCh38/hg38)
Size:
2,102 bases
Orientation:
Plus strand
chr14:102,027,688-102,029,789
(GRCh37/hg19)
Size:
2,102 bases
Orientation:
Plus strand

Genomic View for DIO3 Gene

Genes around DIO3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DIO3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DIO3 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for DIO3 Gene

Proteins for DIO3 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for DIO3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P55073-IOD3_HUMAN
    Recommended name:
    Thyroxine 5-deiodinase
    Protein Accession:
    P55073
    Secondary Accessions:
    • G3XAM0
    • Q8WVN5

    Protein attributes for DIO3 Gene

    Size:
    304 amino acids
    Molecular mass:
    33947 Da
    Quaternary structure:
    • Homodimer. May undergo minor heretodimerization with DIO1 and DIO2.
    SequenceCaution:
    • Sequence=AAB35616.2; Type=Frameshift; Positions=21; Evidence={ECO:0000305}; Sequence=AAH17717.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

neXtProt entry for DIO3 Gene

Protein Expression for DIO3 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for DIO3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DIO3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for DIO3 Gene

Domains & Families for DIO3 Gene

Gene Families for DIO3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted membrane proteins

Protein Domains for DIO3 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for DIO3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P55073

UniProtKB/Swiss-Prot:

IOD3_HUMAN :
  • Belongs to the iodothyronine deiodinase family.
Family:
  • Belongs to the iodothyronine deiodinase family.
genes like me logo Genes that share domains with DIO3: view

Function for DIO3 Gene

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  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for DIO3 Gene

UniProtKB/Swiss-Prot Function:
Responsible for the deiodination of T4 (3,5,3,5-tetraiodothyronine) into RT3 (3,3,5-triiodothyronine) and of T3 (3,5,3-triiodothyronine) into T2 (3,3-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development.
UniProtKB/Swiss-Prot CatalyticActivity:
3,3,5-triiodo-L-thyronine + iodide + acceptor + H(+) = L-thyroxine + reduced acceptor.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=4.3 nM for L-thyroxine {ECO:0000269 PubMed:12746313}; Vmax=1.4 pmol/min/mg enzyme {ECO:0000269 PubMed:12746313};
GENATLAS Biochemistry:
iodothyronine 5-deiodinase type III,selenocysteine containing,catalyzing tyrosyl ring deiodination,highly expressed in the placenta and several fetal tissues,restricted to the skin an central nervous system

Enzyme Numbers (IUBMB) for DIO3 Gene

Gene Ontology (GO) - Molecular Function for DIO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004800 thyroxine 5-deiodinase activity TAS --
GO:0016491 oxidoreductase activity IEA --
GO:0033798 thyroxine 5-deiodinase activity IEA --
genes like me logo Genes that share ontologies with DIO3: view
genes like me logo Genes that share phenotypes with DIO3: view

Animal Models for DIO3 Gene

MGI Knock Outs for DIO3:

Animal Model Products

miRNA for DIO3 Gene

miRTarBase miRNAs that target DIO3

Clone Products

No data available for Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DIO3 Gene

Localization for DIO3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DIO3 Gene

Cell membrane; Single-pass type II membrane protein. Endosome membrane; Single-pass type II membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DIO3 gene
Compartment Confidence
plasma membrane 5
endosome 3
mitochondrion 2
nucleus 2
golgi apparatus 2
extracellular 1
cytosol 1

Gene Ontology (GO) - Cellular Components for DIO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome IEA --
GO:0005886 plasma membrane TAS --
GO:0010008 endosome membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with DIO3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for DIO3 Gene

Pathways & Interactions for DIO3 Gene

genes like me logo Genes that share pathways with DIO3: view

Interacting Proteins for DIO3 Gene

Selected Interacting proteins: P55073-IOD3_HUMAN for DIO3 Gene via IID

GPS-Prot Interaction Network for DIO3

Gene Ontology (GO) - Biological Process for DIO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006590 thyroid hormone generation TAS --
GO:0006915 apoptotic process IEA --
GO:0008150 biological_process ND --
GO:0040018 positive regulation of multicellular organism growth IEA --
GO:0042403 thyroid hormone metabolic process IBA --
genes like me logo Genes that share ontologies with DIO3: view

No data available for SIGNOR curated interactions for DIO3 Gene

Drugs & Compounds for DIO3 Gene

Products:

  1. Drug

(11) Drugs for DIO3 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Levothyroxine Approved Pharma 0
Iopodic acid Approved, Investigational, Withdrawn Pharma Target, antagonist 0
Iodide Approved, Investigational Pharma 0
Liothyronine Approved, Vet_approved Pharma 0

(8) Additional Compounds for DIO3 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • H+
  • H(+)
  • Hydrogen cation
  • Hydron
  • Proton
I(-)
  • [HI]
  • HI
  • Hydriodic acid
  • Hydrogeniodid
  • Hydroiodic acid
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
 77074-49-8
genes like me logo Genes that share compounds with DIO3: view

Transcripts for DIO3 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for DIO3 Gene

(1) REFSEQ mRNAs :
(4) Additional mRNA sequences :
(38) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for DIO3 Gene

Deiodinase, iodothyronine, type III:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for DIO3 Gene

No ASD Table

Relevant External Links for DIO3 Gene

GeneLoc Exon Structure for
DIO3
ECgene alternative splicing isoforms for
DIO3

Expression for DIO3 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for DIO3 Gene

mRNA expression in normal human tissues for DIO3 Gene
mRNA expression by GTEx for DIO3 GenemRNA expression by BioGPS for DIO3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DIO3 Gene

This gene is overexpressed in Cervix - Endocervix (x5.6), Vagina (x5.2), and Ovary (x4.3).

Protein differential expression in normal tissues from HIPED for DIO3 Gene

This gene is overexpressed in Colon muscle (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for DIO3 Gene



Protein tissue co-expression partners for DIO3 Gene

NURSA nuclear receptor signaling pathways regulating expression of DIO3 Gene:

DIO3

SOURCE GeneReport for Unigene cluster for DIO3 Gene:

Hs.49322

mRNA Expression by UniProt/SwissProt for DIO3 Gene:

P55073-IOD3_HUMAN
Tissue specificity: Expressed in placenta and several fetal tissues.

Evidence on tissue expression from TISSUES for DIO3 Gene

  • Intestine(4)
  • Thyroid gland(2.7)
genes like me logo Genes that share expression patterns with DIO3: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for DIO3 Gene

Orthologs for DIO3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for DIO3 Gene

Organism Taxonomy Gene Similarity Type Details
dog
(Canis familiaris)
 Mammalia DIO3 33
  • 90.57 (n)
cow
(Bos Taurus)
 Mammalia DIO3 34 33
  • 88.82 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Dio3 16 34 33
  • 87.79 (n)
rat
(Rattus norvegicus)
 Mammalia Dio3 33
  • 87.72 (n)
oppossum
(Monodelphis domestica)
 Mammalia DIO3 34
  • 62 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves DIO3 33
  • 73.04 (n)
tropical clawed frog
(Silurana tropicalis)
 Amphibia dio3 33
  • 68.04 (n)
African clawed frog
(Xenopus laevis)
 Amphibia LOC397779 33
zebrafish
(Danio rerio)
 Actinopterygii dio3b 33
  • 67.07 (n)
dio3a 34
  • 58 (a)
 OneToOne
-- 33
Species where no ortholog for DIO3 was found in the sources mined by GeneCards:
  • 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)
  • chimpanzee (Pan troglodytes)
  • 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)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • 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 DIO3 Gene

ENSEMBL:
Gene Tree for DIO3 (if available)
TreeFam:
Gene Tree for DIO3 (if available)

Paralogs for DIO3 Gene

Paralogs for DIO3 Gene

(2) SIMAP similar genes for DIO3 Gene using alignment to 2 proteins:

  • IOD3_HUMAN
  • G3XAM0_HUMAN
genes like me logo Genes that share paralogs with DIO3: view

Variants for DIO3 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for DIO3 Gene

SNP ID Clin Chr 14 pos Variation AA Info Type
rs1000106689 -- 101,559,469(+) T/C upstream_transcript_variant
rs1000227493 -- 101,562,706(+) A/G 3_prime_UTR_variant
rs1001107414 -- 101,560,676(+) G/T upstream_transcript_variant
rs1001117243 -- 101,560,810(+) C/A upstream_transcript_variant
rs1001925252 -- 101,563,588(+) G/A downstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for DIO3 Gene

Variant ID Type Subtype PubMed ID
dgv1978n100 CNV gain 25217958
dgv388n67 CNV gain 20364138
esv3635530 CNV gain 21293372
nsv1047869 CNV gain 25217958
nsv1071171 CNV deletion 25765185
nsv1143759 CNV deletion 24896259
nsv565879 CNV loss 21841781
nsv565880 CNV loss 21841781
nsv565882 CNV loss 21841781
nsv827060 CNV gain 20364138
nsv827061 CNV gain 20364138
nsv952247 CNV deletion 24416366

Variation tolerance for DIO3 Gene

Residual Variation Intolerance Score: 23.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.85; 17.72% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DIO3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
DIO3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DIO3 Gene

Disorders for DIO3 Gene

MalaCards: The human disease database

(14) MalaCards diseases for DIO3 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hypothyroidism
  • thyroid deficiency
neonatal thyrotoxicosis
hemangioma
fetal alcohol spectrum disorder
  • fetal alcohol syndrome
prader-willi syndrome
  • pws
- elite association - COSMIC cancer census association via MalaCards
Search DIO3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DIO3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with DIO3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DIO3 Gene

Publications for DIO3 Gene

  1. Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. (PMID: 7593630) Salvatore D … Larsen PR (The Journal of clinical investigation 1995) 2 3 4 22 58
  2. The thyroid hormone-inactivating deiodinase functions as a homodimer. (PMID: 18356288) Sagar GD … Bianco AC (Molecular endocrinology (Baltimore, Md.) 2008) 3 4 22 58
  3. Human type 3 iodothyronine selenodeiodinase is located in the plasma membrane and undergoes rapid internalization to endosomes. (PMID: 12419801) Baqui M … Bianco AC (The Journal of biological chemistry 2003) 3 4 22 58
  4. Substitution of cysteine for selenocysteine in the catalytic center of type III iodothyronine deiodinase reduces catalytic efficiency and alters substrate preference. (PMID: 12746313) Kuiper GG … Visser TJ (Endocrinology 2003) 3 4 22 58
  5. Localization of the type 3 iodothyronine deiodinase (DIO3) gene to human chromosome 14q32 and mouse chromosome 12F1. (PMID: 9787088) Hernandez A … St Germain DL (Genomics 1998) 2 3 22 58

Products for DIO3 Gene

Sources for DIO3 Gene

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