Normal Function
The TPO gene provides instructions for making an enzyme called thyroid peroxidase. This enzyme plays a central role in the function of the thyroid gland, a butterfly-shaped tissue in the lower neck. Thyroid peroxidase assists the chemical reaction that adds iodine to a protein called thyroglobulin, a critical step in generating thyroid hormones. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism).
To function properly, thyroid peroxidase must be located in the cell membrane of certain thyroid cells, called follicular cells. Thyroid peroxidase has several different versions (isoforms), which vary by size and location within the cell. Some versions do not function because they are not located in the cell membrane.
Health Conditions Related to Genetic Changes
Congenital hypothyroidism
TPO gene mutations can cause congenital hypothyroidism, a condition characterized by abnormally low levels of thyroid hormones starting from birth. The TPO gene mutations involved in this condition delete, add, or change DNA building blocks (base pairs) in the TPO gene. Some mutations lead to an abnormally small thyroid peroxidase enzyme that breaks apart before it can be inserted into the cell membrane. Other mutations change the enzyme's 3-dimensional shape, preventing it from functioning properly within the cell membrane. Without functional thyroid peroxidase, iodine taken up by the thyroid gland is not added to thyroglobulin. As a result, the production of thyroid hormones is absent or reduced, leading to the features of congenital hypothyroidism. In most affected individuals, the thyroid gland is enlarged (goiter) in an attempt to compensate for reduced hormone production. Because cases caused by TPO gene mutations result from a disruption of thyroid hormone synthesis, they are classified as thyroid dyshormonogenesis.
More About This Health ConditionOther Names for This Gene
- MSA
- PERT_HUMAN
- thyroid microsomal antigen
- thyroperoxidase
- TPX
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bakker B, Bikker H, Vulsma T, de Randamie JS, Wiedijk BM, De Vijlder JJ. Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update). J Clin Endocrinol Metab. 2000 Oct;85(10):3708-12. doi: 10.1210/jcem.85.10.6878. Citation on PubMed
- Cangul H, Aycan Z, Olivera-Nappa A, Saglam H, Schoenmakers NA, Boelaert K, Cetinkaya S, Tarim O, Bober E, Darendeliler F, Bas V, Demir K, Aydin BK, Kendall M, Cole T, Hogler W, Chatterjee VK, Barrett TG, Maher ER. Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community. Clin Endocrinol (Oxf). 2013 Aug;79(2):275-81. doi: 10.1111/cen.12127. Epub 2013 May 6. Citation on PubMed
- Chardes T, Chapal N, Bresson D, Bes C, Giudicelli V, Lefranc MP, Peraldi-Roux S. The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases. Immunogenetics. 2002 Jun;54(3):141-57. doi: 10.1007/s00251-002-0453-9. Epub 2002 May 3. Citation on PubMed
- Kotani T, Umeki K, Kawano J, Suganuma T, Hishinuma A, Ieiri T, Harada S. Partial iodide organification defect caused by a novel mutation of the thyroid peroxidase gene in three siblings. Clin Endocrinol (Oxf). 2003 Aug;59(2):198-206. doi: 10.1046/j.1365-2265.2003.01823.x. Citation on PubMed
- Lee CC, Harun F, Jalaludin MY, Lim CY, Ng KL, Mat Junit S. Functional analyses of C.2268dup in thyroid peroxidase gene associated with goitrous congenital hypothyroidism. Biomed Res Int. 2014;2014:370538. doi: 10.1155/2014/370538. Epub 2014 Mar 17. Citation on PubMed or Free article on PubMed Central
- Nascimento AC, Guedes DR, Santos CS, Knobel M, Rubio IG, Medeiros-Neto G. Thyroperoxidase gene mutations in congenital goitrous hypothyroidism with total and partial iodide organification defect. Thyroid. 2003 Dec;13(12):1145-51. doi: 10.1089/10507250360731550. Citation on PubMed
- Rivolta CM, Esperante SA, Gruneiro-Papendieck L, Chiesa A, Moya CM, Domene S, Varela V, Targovnik HM. Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect. Hum Mutat. 2003 Sep;22(3):259. doi: 10.1002/humu.9175. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.