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Genetics Home Reference: your guide to understanding genetic conditions
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PAX8

Reviewed August 2015

What is the official name of the PAX8 gene?

The official name of this gene is “paired box 8.”

PAX8 is the gene's official symbol. The PAX8 gene is also known by other names, listed below.

What is the normal function of the PAX8 gene?

The PAX8 gene belongs to a family of genes that play critical roles in the formation of tissues and organs during embryonic development. The PAX gene family is also important for maintaining the normal function of certain cells after birth. To carry out these roles, the PAX genes provide instructions for making proteins that attach to specific areas of DNA. By attaching to critical DNA regions, these proteins help control the activity of particular genes (gene expression). On the basis of this action, PAX proteins are called transcription factors.

During embryonic development, the PAX8 protein is thought to activate genes involved in the formation of the kidney and the thyroid gland. The thyroid gland is a butterfly-shaped tissue in the lower neck. It releases hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Following birth, the PAX8 protein regulates several genes involved in the production of thyroid hormones.

Does the PAX8 gene share characteristics with other genes?

The PAX8 gene belongs to a family of genes called homeobox (homeoboxes). It also belongs to a family of genes called PAX (paired boxes).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the PAX8 gene related to health conditions?

congenital hypothyroidism - caused by mutations in the PAX8 gene

At least 15 mutations in this gene cause congenital hypothyroidism, a condition characterized by abnormally low levels of thyroid hormones starting from birth. Other PAX8 gene mutations only mildly reduce thyroid hormone levels or have no detectable effect. Sometimes, identical mutations in members of the same family have different effects.

Most mutations change one of the building blocks (amino acids) used to make the PAX8 protein. Other mutations disrupt protein production, resulting in an abnormally small version of the PAX8 protein. Nearly all PAX8 gene mutations prevent the PAX8 protein from effectively binding to DNA. One mutation alters interactions between the PAX8 protein and other transcription factors. As a result, the PAX8 protein cannot perform its role in regulating the activity of certain genes.

The thyroid gland is unusually small in people with PAX8 gene mutations. This finding suggests that PAX8 gene mutations disrupt the normal growth or survival of thyroid cells during embryonic development. As a result, the thyroid gland is reduced in size and may be unable to produce the normal amount of thyroid hormones. Because cases caused by PAX8 gene mutations are due to a problem with development of the thyroid gland, they are classified as thyroid dysgenesis.

tumors - associated with the PAX8 gene

The PAX8 gene is sometimes involved in the formation of thyroid tumors (neoplasms). In these cases, abnormal growth affects particular cells called follicular thyroid cells. Some of these growths, called follicular adenomas, are noncancerous (benign). Other tumors, known as follicular carcinomas, are cancerous (malignant). In some of these neoplasms, the PAX8 gene on chromosome 2 is fused with the PPARG gene on chromosome 3. The fusion results when segments of the two chromosomes are rearranged (translocated). It remains unclear how the fused PAX8-PPARG gene affects the growth of follicular thyroid cells, or why some neoplasms become cancerous while others are benign. It is likely that the fused gene disrupts the normal control of cell division or triggers new cell activities that promote tumor formation.

Where is the PAX8 gene located?

Cytogenetic Location: 2q13

Molecular Location on chromosome 2: base pairs 113,215,996 to 113,278,949

The PAX8 gene is located on the long (q) arm of chromosome 2 at position 13.

The PAX8 gene is located on the long (q) arm of chromosome 2 at position 13.

More precisely, the PAX8 gene is located from base pair 113,215,996 to base pair 113,278,949 on chromosome 2.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PAX8?

You and your healthcare professional may find the following resources about PAX8 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the PAX8 gene or gene products?

  • paired box gene 8
  • PAX8_HUMAN

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PAX8?

acids ; benign ; cell ; cell division ; chromosome ; congenital ; DNA ; dysgenesis ; embryonic ; gene ; gene expression ; hormone ; hypothyroidism ; kidney ; metabolism ; mutation ; neoplasms ; protein ; thyroid ; thyroid hormones ; tissue ; transcription ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Cheung L, Messina M, Gill A, Clarkson A, Learoyd D, Delbridge L, Wentworth J, Philips J, Clifton-Bligh R, Robinson BG. Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab. 2003 Jan;88(1):354-7. (http://www.ncbi.nlm.nih.gov/pubmed/12519876?dopt=Abstract)
  • Grasberger H, Ringkananont U, Lefrancois P, Abramowicz M, Vassart G, Refetoff S. Thyroid transcription factor 1 rescues PAX8/p300 synergism impaired by a natural PAX8 paired domain mutation with dominant negative activity. Mol Endocrinol. 2005 Jul;19(7):1779-91. Epub 2005 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/15718293?dopt=Abstract)
  • Komatsu M, Takahashi T, Takahashi I, Nakamura M, Takahashi I, Takada G. Thyroid dysgenesis caused by PAX8 mutation: the hypermutability with CpG dinucleotides at codon 31. J Pediatr. 2001 Oct;139(4):597-9. (http://www.ncbi.nlm.nih.gov/pubmed/11598612?dopt=Abstract)
  • Macchia PE, Lapi P, Krude H, Pirro MT, Missero C, Chiovato L, Souabni A, Baserga M, Tassi V, Pinchera A, Fenzi G, Grüters A, Busslinger M, Di Lauro R. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nat Genet. 1998 May;19(1):83-6. (http://www.ncbi.nlm.nih.gov/pubmed/9590296?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7849)
  • OMIM: PAIRED BOX GENE 8 (http://omim.org/entry/167415)
  • Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet. 2005 May;42(5):379-89. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15863666?dopt=Abstract)
  • Pasca di Magliano M, Di Lauro R, Zannini M. Pax8 has a key role in thyroid cell differentiation. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13144-9. (http://www.ncbi.nlm.nih.gov/pubmed/11069301?dopt=Abstract)
  • Raman P, Koenig RJ. Pax-8-PPAR-γ fusion protein in thyroid carcinoma. Nat Rev Endocrinol. 2014 Oct;10(10):616-23. doi: 10.1038/nrendo.2014.115. Epub 2014 Jul 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/25069464?dopt=Abstract)
  • Ramos HE, Carré A, Chevrier L, Szinnai G, Tron E, Cerqueira TL, Léger J, Cabrol S, Puel O, Queinnec C, De Roux N, Guillot L, Castanet M, Polak M. Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations. Eur J Endocrinol. 2014 Oct;171(4):499-507. doi: 10.1530/EJE-13-1006. (http://www.ncbi.nlm.nih.gov/pubmed/25214233?dopt=Abstract)
  • Tell G, Pellizzari L, Esposito G, Pucillo C, Macchia PE, Di Lauro R, Damante G. Structural defects of a Pax8 mutant that give rise to congenital hypothyroidism. Biochem J. 1999 Jul 1;341 ( Pt 1):89-93. (http://www.ncbi.nlm.nih.gov/pubmed/10377248?dopt=Abstract)
  • Vilain C, Rydlewski C, Duprez L, Heinrichs C, Abramowicz M, Malvaux P, Renneboog B, Parma J, Costagliola S, Vassart G. Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. J Clin Endocrinol Metab. 2001 Jan;86(1):234-8. (http://www.ncbi.nlm.nih.gov/pubmed/11232006?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2015
Published: August 24, 2015