TPO
Thyroid peroxidase
Also known as: PERT_HUMAN, TPX
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P07202
- Gene
- TPO
- Ensembl
- ENSG00000115705
- Chromosome
- 2
- Canonical length
- 933 aa
- Protein class
- Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins
- Secretome location
- Intracellular and membrane
OverviewNCBI Gene
This gene encodes a membrane-bound glycoprotein. The encoded protein acts as an enzyme and plays a central role in thyroid gland function. The protein functions in the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine. Mutations in this gene are associated with several disorders of thyroid hormonogenesis, including congenital hypothyroidism, congenital goiter, and thyroid hormone organification defect IIA. Multiple transcript variants encoding distinct isoforms have been identified for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2011]
Canonical amino-acid sequenceUniProt
933 residues, UniProt reviewed canonical sequence.
>P07202|TPO
1 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR
61 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS
121 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV
181 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD
241 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD
301 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG
361 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA
421 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT
481 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR
541 GLLARPAKLQ VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL
601 PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG PLFACLIGKQ
661 MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG LTRVPMDAFQ VGKFPEDFES
721 CDSITGMNLE AWRETFPQDD KCGFPESVEN GDFVHCEESG RRVLVYSCRH GYELQGREQL
781 TCTQEGWDFQ PPLCKDVNEC ADGAHPPCHA SARCRNTKGG FQCLCADPYE LGDDGRTCVD
841 SGRLPRVTWI SMSLAALLIG GFAGLTSTVI CRWTRTGTKS TLPISETGGG TPELRCGKHQ
901 AVGTSPQRAA AQDSEQESAG MEGRDTHRLP RALLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TPO can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.28
- Highest tissue expression
- 1,388 nTPM
Expression across tissuesHPA
Tissue
- thyroid gland: 1,388 nTPM
- spleen: 19 nTPM
- adipose tissue: 11 nTPM
- heart muscle: 9.4 nTPM
- breast: 9 nTPM
- tongue: 5.2 nTPM
Single-cell type
- oocytes: 88 nCPM
- vascular endothelial cells: 19 nCPM
- late spermatids: 11 nCPM
- peritubular myoid cells: 6.2 nCPM
- lymphatic endothelial cells: 5.2 nCPM
- late primary spermatocytes: 4.6 nCPM
Immune cell
- memory CD4 T-cell: 2 nTPM
- T-reg: 1.2 nTPM
- total PBMC: 0.2 nTPM
- memory CD8 T-cell: 0.1 nTPM
- naive CD8 T-cell: 0.1 nTPM
- basophil: 0 nTPM
Brain region
- cerebral cortex: 1.8 nTPM
- white matter: 1.3 nTPM
- hypothalamus: 1.1 nTPM
- medulla oblongata: 0.9 nTPM
- pons: 0.9 nTPM
- spinal cord: 0.9 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TPO.
Disease | AllUniProt
Conditions TPO is implicated in, by any mechanism.
- Thyroid dyshormonogenesis 2A (TDH2A) MIM:274500
Disease | GeneticClinVar
122 pathogenic / likely-pathogenic of 873 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Deficiency of iodide peroxidase
- Congenital hypothyroidism
- TPO-related disorder
- 7 conditions
- Neurodevelopmental disorder
Disease | ImmuneIEDB
Conditions an epitope on TPO was assayed in.
- autoimmune thyroiditis B and T cell
- Graves' disease B and T cell
- endemic goiter T cell
- multiple sclerosis B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against TPO are reported. Each links to that disease's full target list.
- Thyroiditis, Autoimmune 455
- Hypothyroidism 383
- Graves Disease 287
- Hashimoto Disease 237
- Diabetes Mellitus, Type 1 152
- Hyperthyroidism 128
- Abortion, Spontaneous 47
- Infertility, Female 37
- Thyroiditis 37
- Diabetes Mellitus, Type 2 33
- Abortion, Habitual 32
- Celiac Disease 29
- Urticaria 29
- Hepatitis C, Chronic 26
- Hepatitis C 24
- Arthritis, Rheumatoid 20
- Encephalitis 20
- Breast Neoplasms 18
- Lupus Erythematosus, Systemic 17
- Vitiligo 17
Showing 20 of 141 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for TPO from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
2,380 publications
- Autoimmune Encephalitis Misdiagnosis in Adults.
2023 · JAMA Neurol · RCR 32.4 · 216 citations - Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.
2000 · Ann Intern Med · RCR 24.3 · 898 citations - Risk factors for postpartum depression: An evidence-based systematic review of systematic reviews and meta-analyses.
2020 · Asian J Psychiatr · RCR 21.5 · 251 citations - Molecular Mechanisms in Autoimmune Thyroid Disease.
2023 · Cells · RCR 20.4 · 145 citations - Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
2024 · Thyroid · RCR 17.2 · 56 citations
Show 20 more of 2,380 total
- Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.
2019 · JAMA · RCR 16.8 · 261 citations - Thyroid disease in pregnancy: new insights in diagnosis and clinical management.
2017 · Nat Rev Endocrinol · RCR 15.1 · 293 citations - Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications.
2006 · J Clin Endocrinol Metab · RCR 14.8 · 461 citations - Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases.
2017 · Front Immunol · RCR 14.7 · 309 citations - Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies.
1990 · JAMA · RCR 12.5 · 322 citations - Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception.
2019 · N Engl J Med · RCR 12.4 · 188 citations - Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.
2019 · Proc Nutr Soc · RCR 11.2 · 171 citations - Thyroid autoantibodies.
2023 · J Clin Pathol · RCR 11.1 · 57 citations - Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions.
1991 · J Clin Endocrinol Metab · RCR 10.9 · 260 citations - Iodine Status and Prevalence of Thyroid Disorders After Introduction of Mandatory Universal Salt Iodization for 16 Years in China: A Cross-Sectional Study in 10 Cities.
2016 · Thyroid · RCR 10.5 · 223 citations - Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT).
2000 · Eur J Endocrinol · RCR 10.4 · 336 citations - Most Patients With Autoimmune Chronic Spontaneous Urticaria Also Have Autoallergic Urticaria, but Not ViceVersa.
2023 · J Allergy Clin Immunol Pract · RCR 10.2 · 67 citations - Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders.
1994 · J Clin Endocrinol Metab · RCR 10.1 · 267 citations - Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy.
2010 · J Clin Endocrinol Metab · RCR 9.8 · 266 citations - Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy.
2010 · J Clin Endocrinol Metab · RCR 9.7 · 255 citations - Metabolic Characteristics of Hashimoto's Thyroiditis Patients and the Role of Microelements and Diet in the Disease Management-An Overview.
2022 · Int J Mol Sci · RCR 9.5 · 78 citations - Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase.
2011 · J Allergy Clin Immunol · RCR 9.4 · 273 citations - Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management.
2018 · J Formos Med Assoc · RCR 9 · 150 citations - Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study.
2014 · Thyroid · RCR 8.4 · 188 citations - High prevalence of thyroid autoantibodies in a prospective series of patients with chronic hepatitis C before interferon therapy.
1993 · Hepatology · RCR 8.3 · 230 citations
Reference: B cellIEDB
10 publications
- High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.
2016 · Mol Cell Proteomics · RCR 2.5 · 66 citations - Thyroperoxidase, but not the thyrotropin receptor, contains sequential epitopes recognized by autoantibodies in recombinant peptides expressed in the pUEX vector.
1991 · J Clin Endocrinol Metab · RCR 2.5 · 78 citations - Identification of an immunodominant region recognized by human autoantibodies in a three-dimensional model of thyroid peroxidase.
2000 · Endocrinology · RCR 1.2 · 44 citations - Unique autoantibody epitopes in an immunodominant region of thyroid peroxidase.
1996 · J Biol Chem · RCR 1.2 · 39 citations - Localization of the discontinuous immunodominant region recognized by human anti-thyroperoxidase autoantibodies in autoimmune thyroid diseases.
2003 · J Biol Chem · RCR 1.1 · 42 citations
Show 5 more
- Evaluation of conformational epitopes on thyroid peroxidase by antipeptide antibody binding and mutagenesis.
2004 · Clin Exp Immunol · RCR 0.8 · 26 citations - Epitope recognition patterns of thyroid peroxidase autoantibodies in healthy individuals and patients with Hashimoto's thyroiditis*.
2008 · Clin Endocrinol (Oxf) · RCR 0.6 · 19 citations - Proportion of antibodies to the A and B immunodominant regions of thyroid peroxidase in Graves and Hashimoto disease.
2004 · Autoimmunity · RCR 0.5 · 17 citations - New insights into the conformational dominant epitopes on thyroid peroxidase recognized by human autoantibodies.
2005 · Endocrinology · RCR 0.4 · 15 citations - The key residues in the immunodominant region 353-363 of human thyroid peroxidase were identified.
2006 · Int Immunol · RCR 0.3 · 10 citations
Reference: T cellIEDB
10 publications
- Evidence of a combined cytotoxic thyroglobulin and thyroperoxidase epitope-specific cellular immunity in Hashimoto's thyroiditis.
2012 · J Clin Endocrinol Metab · RCR 1.8 · 56 citations - Thyrotropin-receptor and thyroid peroxidase-specific T cell clones and their cytokine profile in autoimmune thyroid disease.
1997 · J Clin Endocrinol Metab · RCR 1.5 · 60 citations - T cell responses to synthetic thyroid peroxidase peptides in autoimmune thyroid disease.
1991 · Clin Exp Immunol · RCR 1.1 · 43 citations - Human self-reactive T cell clones expressing identical T cell receptor beta chains differ in their ability to recognize a cryptic self-epitope.
1996 · J Exp Med · RCR 1 · 48 citations - Degenerate self-reactive human T-cell receptor causes spontaneous autoimmune disease in mice.
2004 · Nat Med · RCR 1 · 42 citations
Show 5 more
- Proliferative responses of peripheral blood mononuclear cells from patients with autoimmune thyroid diseases to synthetic peptide epitopes of human thyroid peroxidase.
1992 · Autoimmunity · RCR 0.8 · 26 citations - Human autoantibodies modulate the T cell epitope repertoire but fail to unmask a pathogenic cryptic epitope.
2005 · J Immunol · RCR 0.5 · 22 citations - Proliferative responses of T-cells to thyroid antigens and synthetic thyroid peroxidase peptides in autoimmune thyroid disease.
1995 · J Clin Endocrinol Metab · RCR 0.5 · 19 citations - Identification of novel HLA-A0201-restricted T-cell epitopes against thyroid antigens in autoimmune thyroid diseases.
2020 · Endocrine · RCR 0.3 · 5 citations - T cells involved in human autoimmune disease are resistant to tolerance induction.
1993 · J Immunol · RCR 0.3 · 14 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.11
- gnomAD pLI
- 0
- gnomAD missense Z
- 0
- DepMap mean gene effect
- 0.03
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- embryonic hemopoiesis
- hormone biosynthetic process
- hydrogen peroxide catabolic process
- response to oxidative stress
- thyroid hormone generation
Molecular functions
- calcium ion binding
- heme binding
- peroxidase activity
- iodide peroxidase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- EGF-type aspartate/asparagine hydroxylation site
- Sushi/SCR/CCP domain
- EGF-like domain
- EGF-like calcium-binding domain
- Haem peroxidase superfamily
- EGF-like calcium-binding, conserved site
- Haem peroxidase, animal-type
- Sushi/SCR/CCP superfamily
- Haem peroxidase domain superfamily, animal type
- NOTCH1, EGF-like calcium-binding domain
- Sushi repeat (SCR repeat)
- Animal haem peroxidase
- Calcium-binding EGF domain
- Thyroid peroxidase
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TPO in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TPO as an antibody target. Whether an autoantibody or antibody against TPO could matter depends on whether native TPO is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TPO is annotated at the cell surface, where native TPO is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label TPO as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...