Details for: IYD

Gene ID: 389434

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: IYD

Ensembl ID: ENSG00000009765

Description: iodotyrosine deiodinase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • goblet cell CL0000160
    CSI 3.64
    rCSI 3.44%
    PRS 98.72
  • intestine goblet cell CL0019031
    CSI 3.39
    rCSI 3.01%
    PRS 98.59
  • hepatocyte CL0000182
    CSI 3.16
    rCSI 5.65%
    PRS 98.14
  • colon epithelial cell CL0011108
    CSI 2.82
    rCSI 2.95%
    PRS 98.87
  • centrilobular region hepatocyte CL0019029
    CSI 2.69
    rCSI 7.03%
    PRS 97.54
  • colonocyte CL1000347
    CSI 2.63
    rCSI 3.77%
    PRS 98.81
  • enterocyte CL0000584
    CSI 2.33
    rCSI 3.75%
    PRS 98.06
  • epithelial cell of proximal tubule CL0002306
    CSI 2.3
    rCSI 5.63%
    PRS 97.11
  • colon goblet cell CL0009039
    CSI 1.6
    rCSI 3.81%
    PRS 99.09

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [IYD](/details-gene/389434) (Iodotyrosine Deiodinase) is a protein-coding gene located on chromosome 6q25.1. It encodes a crucial flavoprotein enzyme responsible for the deiodination of mono- and di-iodotyrosine, which are byproducts of thyroid hormone synthesis. This function is essential for the intrathyroidal recycling and conservation of iodide, a key component of thyroid hormones. Consistent with its metabolic function, expression data shows that **Overall**, [IYD](/details-gene/389434) is a significant gene in metabolically active and secretory cell types, including various intestinal epithelial cells like [goblet cells](/details-cell/CL0000160) and [hepatocytes](/details-cell/CL0000182). Clinically, loss-of-function mutations in [IYD](/details-gene/389434) are associated with congenital hypothyroidism, goiter, and iodotyrosine deiodinase deficiency (OMIM: [274800](https://omim.org/entry/274800)), highlighting its indispensable role in maintaining thyroid homeostasis ([Link](https://doi.org/10.1056/nejmoa0706819)). ## Cellular Roles and Expression Landscape The expression profile of [IYD](/details-gene/389434) underscores its specialized role in tissues with high metabolic and secretory activity, particularly those involved in nutrient processing and hormone metabolism. **Overall**, the gene shows the highest significance in epithelial cell populations of the gastrointestinal tract and liver. It is a top marker in [goblet cells](/details-cell/CL0000160) (CSI: 3.64), [intestine goblet cells](/details-cell/CL0019031) (CSI: 3.39), [colon epithelial cells](/details-cell/CL0011108) (CSI: 2.82), [colonocytes](/details-cell/CL1000347) (CSI: 2.63), and [enterocytes](/details-cell/CL0000584) (CSI: 2.33). This pronounced expression in the intestinal lining suggests a potential role beyond the thyroid, possibly in local iodide handling, absorption, or detoxification within the gut environment. Furthermore, [IYD](/details-gene/389434) is highly significant in [hepatocytes](/details-cell/CL0000182) (CSI: 3.16) and [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 2.69), which is consistent with the liver's central role in systemic metabolism, including the breakdown and processing of hormones. Significant expression is also noted in [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney (CSI: 2.30), a site of extensive metabolic reabsorption. This collective expression pattern points to a conserved function for [IYD](/details-gene/389434) in iodide salvage and management across key metabolic organs. ## Pathways and Molecular Function The function of [IYD](/details-gene/389434) is well-defined within the context of thyroid hormone metabolism. Its primary molecular function, as annotated by Gene Ontology, is **Iodotyrosine deiodinase activity** ([GO:0140616](https://www.ebi.ac.uk/QuickGO/term/GO:0140616)), which directly contributes to the biological process of **Thyroid hormone metabolic process** ([GO:0042403](https://www.ebi.ac.uk/QuickGO/term/GO:0042403)). The enzyme utilizes FMN (flavin mononucleotide) as a cofactor, reflected by its annotation for **Fmn binding** ([GO:0010181](https://www.ebi.ac.uk/QuickGO/term/GO:0010181)), and employs a sophisticated enzymatic mechanism that can switch between one- and two-electron chemistry depending on the substrate ([Link](https://doi.org/10.1074/jbc.m114.605964)). This function is a key step in the Reactome pathway **Thyroxine biosynthesis** ([R-HSA-209968](https://reactome.org/content/detail/R-HSA-209968)), where it prevents the loss of iodide from the thyroid gland. Cellular component annotations place the protein at the **Plasma membrane** ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)) and in the **Cytoplasmic vesicle membrane** ([GO:0030659](https://www.ebi.ac.uk/QuickGO/term/GO:0030659)), which is consistent with research identifying it as a transmembrane protein that recycles iodide near the site of thyroglobulin iodination ([Link](https://doi.org/10.1096/fj.04-2023fje)). Its broad involvement in **Metabolism of amino acids and derivatives** ([R-HSA-71291](https://reactome.org/content/detail/R-HSA-71291)) further situates its role within the larger framework of metabolic homeostasis. ## Research Directions While the role of [IYD](/details-gene/389434) in the thyroid is well-established, its high and specific expression in extra-thyroidal tissues like the intestine and liver presents new avenues for investigation. Understanding these non-canonical roles could provide insights into local iodide homeostasis and its impact on organ function. **Testable Hypotheses:** 1. The high expression of [IYD](/details-gene/389434) in intestinal [goblet cells](/details-cell/CL0000160) and [colonocytes](/details-cell/CL1000347) may serve a protective function by locally deiodinating dietary iodotyrosines, thereby regulating iodide availability for the gut microbiome and preventing potential oxidative stress in the intestinal epithelium. 2. In [hepatocytes](/details-cell/CL0000182), [IYD](/details-gene/389434) may function as a systemic scavenger, capturing and deiodinating iodotyrosines released into circulation from peripheral tissues, thus contributing to the whole-body iodide pool and complementing the primary salvage pathway in the thyroid. **Proposed Experiment:** To test the hypothesis regarding the role of [IYD](/details-gene/389434) in the gut, an intestinal epithelial cell-specific knockout mouse model (e.g., *Iyd*flox/flox; Villin-CreERT2) could be generated. Following tamoxifen-induced deletion of [IYD](/details-gene/389434) in the adult gut, these mice and their wild-type littermates could be fed diets with varying levels of iodide and iodotyrosine. The impact of [IYD](/details-gene/389434) deletion could be assessed by measuring fecal and portal vein iodide/iodotyrosine levels via mass spectrometry, analyzing changes in gut microbiome composition using 16S rRNA sequencing, and evaluating markers of oxidative stress and inflammation in the intestinal mucosa via qPCR and histology. **Therapeutic Potential:** The clinical relevance of [IYD](/details-gene/389434) is primarily linked to loss-of-function mutations causing hypothyroidism ([Link](https://doi.org/10.1056/nejmoa0706819)). Therefore, therapeutic strategies would likely focus on **activation** or restoration of function. For patients with [IYD](/details-gene/389434) deficiency, gene therapy to restore enzymatic activity in the thyroid could be a potential long-term cure, obviating the need for lifelong hormone replacement. Pharmacological chaperones or small-molecule activators that stabilize misfolded mutant IYD protein or enhance its catalytic activity could also be explored. Inhibition of [IYD](/details-gene/389434) is unlikely to be a therapeutic goal, given its essential role in iodide conservation.

Genular Protein ID: 3507407203

Symbol: IYD1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6PHW0 C9JFW2 Q2VPW0 Q2VPW1 Q5F1L5 Q5F1L6 Q5THM4 Q6ZP69 Q7Z7D7 Q7Z7D8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChEBI 37 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 DrugBank 1 EC 1 EMBL 10 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 7 RNAct 1 Reactome 1 RefSeq 4 Rhea 10 SABIO-RK 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15289438

Title: Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site.

PubMed ID: 15289438

DOI: 10.1096/fj.04-2023fje

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 28157283

Title: Active Site Binding Is Not Sufficient for Reductive Deiodination by Iodotyrosine Deiodinase.

PubMed ID: 28157283

DOI: 10.1021/acs.biochem.6b01308

PubMed ID: 25395621

Title: A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate.

PubMed ID: 25395621

DOI: 10.1074/jbc.m114.605964

PubMed ID: 18434651

Title: Mutations in the iodotyrosine deiodinase gene and hypothyroidism.

PubMed ID: 18434651

DOI: 10.1056/nejmoa0706819

Sequence Information:

  • Length: 289
  • Mass: 33360
  • Checksum: B73560A682BF6045
  • Sequence:
    • MYFLTPILVA ILCILVVWIF KNADRSMEKK KGEPRTRAEA RPWVDEDLKD SSDLHQAEED 
ADEWQESEEN VEHIPFSHNH YPEKEMVKRS QEFYELLNKR RSVRFISNEQ VPMEVIDNVI 
RTAGTAPSGA HTEPWTFVVV KDPDVKHKIR KIIEEEEEIN YMKRMGHRWV TDLKKLRTNW 
IKEYLDTAPI LILIFKQVHG FAANGKKKVH YYNEISVSIA CGILLAALQN AGLVTVTTTP 
LNCGPRLRVL LGRPAHEKLL MLLPVGYPSK EATVPDLKRK PLDQIMVTV

Genular Protein ID: 364337329

Symbol: Q2VPV9_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q2VPV9

Database IDs:

ARBA 13 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 22 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 3 Gene3D 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 RefSeq 1 Rhea 8 SUPFAM 1

Sequence Information:

  • Length: 165
  • Mass: 18917
  • Checksum: EED94C89A5B21162
  • Sequence:
    • MLMNGKNQKK MLNTSPSLIT TILRRKWLRG LRNFMNFSIR DGTAPSGAHT EPWTFVVVKD 
PDVKHKIRKI IEEEEEINYM KRMGHRWVTD LKKLRTNWIK EYLDTAPILI LIFKQVHGFA 
ANGKKKVHYY NEISVSIACG ILLAALQNAG LVTVTTTPLN CGPRL