Details for: TPO

Gene ID: 7173

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: TPO

Ensembl ID: ENSG00000115705

Description: thyroid peroxidase

Cell Significance Landscape

Associated with

Significant Cells

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

  • blood vessel endothelial cell CL0000071
    CSI 9.16
    rCSI 19.01%
    PRS 99.44
  • capillary endothelial cell CL0002144
    CSI 4.87
    rCSI 8.93%
    PRS 99.65
  • cardiac endothelial cell CL0010008
    CSI 3.28
    rCSI 13.23%
    PRS 99.74
  • endothelial cell of vascular tree CL0002139
    CSI 1.97
    rCSI 10.78%
    PRS 98.42

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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Legend:
  • Query Gene
  • 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 [TPO](/details-gene/7173), or thyroid peroxidase, is a heme-containing glycoprotein that functions as a key enzyme in the biosynthesis of thyroid hormones. Located primarily on the apical plasma membrane of thyroid follicular cells, it catalyzes the iodination of tyrosine residues on thyroglobulin and the subsequent coupling of these residues to form thyroxine (T4) and triiodothyronine (T3). Genetic defects in [TPO](/details-gene/7173) are a well-established cause of congenital hypothyroidism and goiter, a condition associated with total iodide organification defects ([274500](https://omim.org/entry/274500)) as documented in numerous studies ([Link](https://pubmed.ncbi.nlm.nih.gov/7550241/), [Link](https://doi.org/10.1210/jcem.82.2.3729)). While its role in the thyroid is canonical, expression analysis indicates a significant and specific presence in various endothelial cell populations, suggesting a potentially broader, though less understood, physiological function. ## Cellular Roles and Expression Landscape The primary and most well-characterized role of [TPO](/details-gene/7173) is within thyroid follicular cells, where it is essential for hormone production. However, expression data reveals a notable and highly significant signature in the vascular endothelium. - **Overall**, the gene demonstrates its highest significance in endothelial lineages. It is a top marker for [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 9.16), [capillary endothelial cell](/details-cell/CL0002144) (CSI: 4.87), [cardiac endothelial cell](/details-cell/CL0010008) (CSI: 3.28), and the broader category of [endothelial cell of vascular tree](/details-cell/CL0002139) (CSI: 1.97). This consistent and high significance across different endothelial subtypes suggests a functional role beyond the thyroid, possibly related to local metabolic or protective processes within the vasculature. The canonical protein structure and its alternate splice variants have been extensively characterized ([Link](https://doi.org/10.1073/pnas.84.16.5555), [Link](https://doi.org/10.1093/nar/18.3.670), [Link](https://doi.org/10.1074/jbc.m209513200)). ## Pathways and Molecular Function The functional annotations for [TPO](/details-gene/7173) strongly reflect its established role in endocrine biology while also providing clues to its potential extra-thyroidal functions. - **Hormone Synthesis:** [TPO](/details-gene/7173) is a central component of the '[Thyroid hormone generation](/details-cell/GO:0006590)' biological process and the '[Thyroxine biosynthesis](/details-cell/R-HSA-209968)' pathway. Its molecular function is defined by its '[peroxidase activity](/details-cell/GO:0004601)' and, more specifically, its '[iodide peroxidase activity](/details-cell/GO:0004447)', which requires '[heme binding](/details-cell/GO:0020037)' and '[calcium ion binding](/details-cell/GO:0005509)'. These activities are critical for organifying iodide, a rate-limiting step in producing thyroid hormones. - **Oxidative Stress Response:** The gene is also linked to processes such as '[cellular oxidant detoxification](/details-cell/GO:0098869)' and '[hydrogen peroxide catabolic process](/details-cell/GO:0042744)'. This suggests that beyond its specific role in hormone synthesis, [TPO](/details-gene/7173) may function as a general peroxidase to mitigate oxidative stress. This function could be particularly relevant in the endothelial cells where it is highly expressed, as the vasculature is constantly exposed to reactive oxygen species. - **Cellular Location:** Consistent with its function as a membrane-bound enzyme acting on extracellular substrates, [TPO](/details-gene/7173) is localized to the '[plasma membrane](/details-cell/GO:0005886)', '[cell surface](/details-cell/GO:0009986)', and '[extracellular space](/details-cell/GO:0005615)'. ## Research Directions While the role of [TPO](/details-gene/7173) in thyroid physiology is well-defined, its significant expression in endothelial cells opens new avenues for investigation. - **Proposed Hypotheses:** 1. [TPO](/details-gene/7173) expression in endothelial cells provides a localized protective mechanism against oxidative damage. Its peroxidase activity may serve to detoxify reactive oxygen species like hydrogen peroxide, thereby preserving vascular integrity and function, independent of its role in systemic hormone synthesis. 2. Endothelial [TPO](/details-gene/7173) may participate in local, non-hormonal iodide metabolism. This activity could influence vasodilation or angiogenesis by modulating local concentrations of iodide or its oxidized intermediates, representing a novel signaling axis in the vasculature. - **Key Experimental Approach:** To test the hypothesis that [TPO](/details-gene/7173) protects endothelial cells from oxidative stress, a functional study using primary human endothelial cells (e.g., HUVECs) could be conducted. One could use CRISPR-Cas9 or siRNA to knock down [TPO](/details-gene/7173) expression. These modified cells, along with wild-type controls, would then be exposed to an oxidative stressor such as H2O2 or angiotensin II. The impact could be assessed by measuring intracellular ROS levels using fluorescent probes, cell viability via apoptosis assays (e.g., Annexin V staining), and the expression of downstream stress-response genes using qRT-PCR or RNA-seq. A greater susceptibility to oxidative stress in the TPO-deficient cells would support this proposed protective function. - **Therapeutic Potential:** Direct inhibition of [TPO](/details-gene/7173) is not a viable therapeutic strategy due to its essential role in producing thyroid hormones, which would lead to iatrogenic hypothyroidism. However, [TPO](/details-gene/7173) is the primary autoantigen in autoimmune thyroid diseases like Hashimoto's thyroiditis and Graves' disease. Therefore, its therapeutic relevance lies in immunology. Strategies aimed at inducing antigen-specific tolerance to [TPO](/details-gene/7173) could potentially treat or prevent the autoimmune destruction of the thyroid gland. Understanding its expression and function in other tissues, such as the endothelium, will be critical to designing safe immunomodulatory therapies that do not have unintended off-target effects.

Genular Protein ID: 3958855602

Symbol: PERT_HUMAN

Name: N/A

UniProtKB Accession Codes:

P07202 P09934 P09935 Q8IUL0 Q8NF94 Q8NF95 Q8NF96 Q8NF97 Q8TCI9

Database IDs:

ABCD 1 AGR 1 Allergome 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 3 CTD 1 ChEBI 39 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 8 DrugCentral 1 EC 5 EMBL 27 Ensembl 5 ExpressionAtlas 1 GO 12 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HPA 1 InParanoid 1 InterPro 12 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 7 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PeroxiBase 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 8 RNAct 1 Reactome 1 RefSeq 7 Rhea 16 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 3475693

Title: Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs.

PubMed ID: 3475693

DOI: 10.1073/pnas.84.16.5555

PubMed ID: 3453124

Title: Complete nucleotide sequence of the human thyroperoxidase-microsomal antigen cDNA.

PubMed ID: 3453124

DOI: 10.1093/nar/15.16.6735

PubMed ID: 2548579

Title: Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene.

PubMed ID: 2548579

DOI: 10.1021/bi00436a054

PubMed ID: 2308857

Title: Nucleotide sequence of the alternatively spliced human thyroid peroxidase cDNA, TPO-2.

PubMed ID: 2308857

DOI: 10.1093/nar/18.3.670

PubMed ID: 12454013

Title: Increasing diversity of human thyroperoxidase generated by alternative splicing. Characterization by molecular cloning of new transcripts with single- and multispliced mRNAs.

PubMed ID: 12454013

DOI: 10.1074/jbc.m209513200

PubMed ID: 3654979

Title: Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase.

PubMed ID: 3654979

DOI: 10.1172/jci113181

PubMed ID: 2383265

Title: Evidence for an alternate splicing in the thyroperoxidase messenger from patients with Graves' disease.

PubMed ID: 2383265

DOI: 10.1016/0006-291x(90)92152-p

PubMed ID: 15561711

Title: Identification of a novel partner of duox: EFP1, a thioredoxin-related protein.

PubMed ID: 15561711

DOI: 10.1074/jbc.m407709200

PubMed ID: 7550241

Title: Identification of five novel inactivating mutations in the human thyroid peroxidase gene by denaturing gradient gel electrophoresis.

PubMed ID: 7550241

DOI: 10.1002/humu.1380060104

PubMed ID: 9024270

Title: Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects.

PubMed ID: 9024270

DOI: 10.1210/jcem.82.2.3729

PubMed ID: 10468986

Title: A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect.

PubMed ID: 10468986

DOI: 10.1046/j.1365-2265.1999.00746.x

PubMed ID: 10084596

Title: Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping.

PubMed ID: 10084596

DOI: 10.1210/jcem.84.3.5541

PubMed ID: 9924196

Title: A novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification defect.

PubMed ID: 9924196

DOI: 10.1677/joe.0.1600267

PubMed ID: 11061528

Title: Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update).

PubMed ID: 11061528

DOI: 10.1210/jcem.85.10.6878

PubMed ID: 11415848

Title: Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism.

PubMed ID: 11415848

DOI: 10.1530/eje.0.1450019

PubMed ID: 11916616

Title: Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism.

PubMed ID: 11916616

DOI: 10.1530/eje.0.1460491

PubMed ID: 12213873

Title: High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide organification defect, and evidence for a founder effect.

PubMed ID: 12213873

DOI: 10.1210/jc.2002-020153

PubMed ID: 11874711

Title: Mutation analysis of thyroid peroxidase gene in Chinese patients with total iodide organification defect: identification of five novel mutations.

PubMed ID: 11874711

DOI: 10.1677/joe.0.1720627

PubMed ID: 12490071

Title: Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach.

PubMed ID: 12490071

DOI: 10.1089/105072502320908277

PubMed ID: 12864797

Title: Partial iodide organification defect caused by a novel mutation of the thyroid peroxidase gene in three siblings.

PubMed ID: 12864797

DOI: 10.1046/j.1365-2265.2003.01823.x

PubMed ID: 12938097

Title: Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect.

PubMed ID: 12938097

DOI: 10.1002/humu.9175

PubMed ID: 12843174

Title: Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect.

PubMed ID: 12843174

DOI: 10.1210/jc.2002-021377

PubMed ID: 16284446

Title: Two novel mutations in the thyroid peroxidase gene with goitrous hypothyroidism.

PubMed ID: 16284446

DOI: 10.1507/endocrj.52.643

PubMed ID: 16684826

Title: Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes.

PubMed ID: 16684826

DOI: 10.1210/jc.2006-0142

PubMed ID: 27305979

Title: Mutations in the genes for thyroglobulin and thyroid peroxidase cause thyroid dyshormonogenesis and autosomal-recessive intellectual disability.

PubMed ID: 27305979

DOI: 10.1038/jhg.2016.62

Sequence Information:

  • Length: 933
  • Mass: 102963
  • Checksum: F67C5F1A4AEE0B29
  • Sequence:
    • MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 
NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 
EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 
YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 
IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 
QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 
RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 
LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 
VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR 
GLLARPAKLQ VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL 
PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG PLFACLIGKQ 
MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG LTRVPMDAFQ VGKFPEDFES 
CDSITGMNLE AWRETFPQDD KCGFPESVEN GDFVHCEESG RRVLVYSCRH GYELQGREQL 
TCTQEGWDFQ PPLCKDVNEC ADGAHPPCHA SARCRNTKGG FQCLCADPYE LGDDGRTCVD 
SGRLPRVTWI SMSLAALLIG GFAGLTSTVI CRWTRTGTKS TLPISETGGG TPELRCGKHQ 
AVGTSPQRAA AQDSEQESAG MEGRDTHRLP RAL

Genular Protein ID: 3336246376

Symbol: Q502Y3_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q502Y3

Database IDs:

ARBA 23 Allergome 1 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 3 CTD 1 ChEBI 31 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 5 EMBL 2 GO 8 Gene3D 3 InterPro 12 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSR 1 PRINTS 1 PROSITE 9 PROSITE-ProRule 2 PeptideAtlas 1 PeroxiBase 1 Pfam 3 PharmGKB 1 RefSeq 4 Rhea 16 SAM 3 SMART 3 SMR 1 SUPFAM 3 UniPathway 1

Citations:

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

Sequence Information:

  • Length: 933
  • Mass: 102937
  • Checksum: C0148BC7787238E7
  • Sequence:
    • MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 
NLKKRGILSA AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 
EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 
YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 
IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 
QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 
RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 
LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 
VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR 
GLLARPAKLQ VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL 
PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG PLFACLIGKQ 
MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG LTRVPMDAFQ VGKFPEDFES 
CDSITGMNLE AWRETFPQDD KCGFPESVEN GDFVHCEESG RRVLVYSCRH GYELQGREQL 
TCTQEGWDFQ PPLCKDVNEC ADGAHPPCHA SARCRNTKGG FQCLCADPYE LGDDGRTCVD 
SGRLPRVTWI SMSLAALLIG GFAGLTSTVI CRWTRTGTKS TLPISETGGG TPELRCGKHQ 
AVGTSPQRAA AQDSEQESAG MEGRDTHRLP RAL

Genular Protein ID: 546288911

Symbol: Q6P534_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6P534

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PROSITE 1 PeptideAtlas 1 PharmGKB 1 RefSeq 4 SAM 1 SMR 1

Citations:

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

Sequence Information:

  • Length: 174
  • Mass: 19308
  • Checksum: 7DB070D17232882E
  • Sequence:
    • MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 
NLKKRGILSA AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 
EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RKMKYKPDHS ETAN