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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed June 2011

What is the official name of the TP63 gene?

The official name of this gene is “tumor protein p63.”

TP63 is the gene's official symbol. The TP63 gene is also known by other names, listed below.

What is the normal function of the TP63 gene?

The TP63 gene provides instructions for making a protein called tumor protein p63 (also known simply as p63). The p63 protein functions as a transcription factor, which means it attaches (binds) to certain regions of DNA and controls the activity of particular genes.

The p63 protein interacts with other proteins to turn many different genes on and off at different times. The action of p63 helps regulate numerous cell activities, including cell growth and division (proliferation), cell maintenance, the process by which cells mature to carry out specific functions (differentiation), the ability of cells to stick to one another (cell adhesion), and the orderly self-destruction of cells (apoptosis).

The p63 protein plays a critical role in early development. It is especially important for the normal development of ectodermal structures, such as the skin, hair, teeth, and nails. Studies suggest that it also plays essential roles in the development of the limbs, facial features, urinary system, and other organs and tissues. In addition to its roles in development, the p63 protein appears to be necessary for the maintenance of various cells and tissues later in life.

How are changes in the TP63 gene related to health conditions?

ankyloblepharon-ectodermal defects-cleft lip/palate syndrome - caused by mutations in the TP63 gene

At least 40 mutations in the TP63 gene have been identified in people with ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome. This condition is a form of ectodermal dysplasia, which is a group of disorders characterized by abnormal development of the skin, hair, nails, teeth, and sweat glands. Other characteristic features of AEC syndrome include partial or complete fusion of the upper and lower eyelids (ankyloblepharon filiforme adnatum) and an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both.

Most of the TP63 gene mutations responsible for AEC syndrome occur in regions of the p63 protein known as the sterile alpha motif (SAM) domain and the transactivation inhibitory (TI) domain. Mutations in these regions interfere with the ability of p63 to turn target genes on and off at the right times. However, it is unclear how these changes lead to abnormal ectodermal development and the specific features of AEC syndrome.

other disorders - caused by mutations in the TP63 gene

Mutations in the TP63 gene cause several additional ectodermal dysplasias with features that overlap those of AEC syndrome. These conditions include ectrodactyly, ectodermal dysplasia, clefting (EEC) syndrome; acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome; and limb-mammary syndrome (LMS). This group of disorders is characterized by varying combinations of ectodermal abnormalities (which affect the skin, hair, nails, teeth, and sweat glands), cleft lip and/or cleft palate, and malformations of the hands and feet.

Mutations in the TP63 gene have also been found to cause split hand/foot malformation type 4 (SHFM4), a condition involving hand and foot malformations without any other signs or symptoms. Additionally, TP63 gene mutations are a rare cause of cleft lip and/or cleft palate that occur without features affecting other parts of the body.

The TP63 gene mutations responsible for these conditions occur in various regions of the TP63 gene and affect the function of the p63 protein in different ways. Some of the known mutations may give the p63 protein a new, abnormal function (described as "gain-of-function" mutations) or lead to a version of the p63 protein that interferes with normal cell activities (described as "dominant-negative" mutations). These changes alter the ability of p63 to interact with other proteins, to turn target genes on and off at the right times, or both. It is unclear how abnormal p63 activity disrupts ectodermal development and leads to the specific features of the TP63-related conditions.

Where is the TP63 gene located?

Cytogenetic Location: 3q28

Molecular Location on chromosome 3: base pairs 189,566,861 to 189,897,279

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The TP63 gene is located on the long (q) arm of chromosome 3 at position 28.

The TP63 gene is located on the long (q) arm of chromosome 3 at position 28.

More precisely, the TP63 gene is located from base pair 189,566,861 to base pair 189,897,279 on chromosome 3.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about TP63?

You and your healthcare professional may find the following resources about TP63 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 TP63 gene or gene products?

  • AIS
  • amplified in squamous cell carcinoma
  • chronic ulcerative stomatitis protein
  • CUSP
  • KET
  • NBP
  • p40
  • p51
  • p51A
  • p51B
  • p53CP
  • p63
  • P63_HUMAN
  • p73L
  • TP53CP
  • TP53L
  • TP73L
  • transformation-related protein 63
  • tumor protein 63
  • tumor protein p53-competing protein

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding TP63?

apoptosis ; carcinoma ; cell ; cell adhesion ; chronic ; cleft palate ; differentiation ; DNA ; domain ; dysplasia ; ectrodactyly ; epidermis ; gene ; malformation ; motif ; palate ; proliferation ; protein ; syndrome ; transcription ; transcription factor ; transformation ; tumor

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


  • Celli J, Duijf P, Hamel BC, Bamshad M, Kramer B, Smits AP, Newbury-Ecob R, Hennekam RC, Van Buggenhout G, van Haeringen A, Woods CG, van Essen AJ, de Waal R, Vriend G, Haber DA, Yang A, McKeon F, Brunner HG, van Bokhoven H. Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell. 1999 Oct 15;99(2):143-53. (
  • Gene Review: TP63-Related Disorders (
  • Koster MI. p63 in skin development and ectodermal dysplasias. J Invest Dermatol. 2010 Oct;130(10):2352-8. doi: 10.1038/jid.2010.119. Epub 2010 May 6. Review. (
  • McGrath JA, Duijf PH, Doetsch V, Irvine AD, de Waal R, Vanmolkot KR, Wessagowit V, Kelly A, Atherton DJ, Griffiths WA, Orlow SJ, van Haeringen A, Ausems MG, Yang A, McKeon F, Bamshad MA, Brunner HG, Hamel BC, van Bokhoven H. Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63. Hum Mol Genet. 2001 Feb 1;10(3):221-9. (
  • NCBI Gene (
  • Rinne T, Bolat E, Meijer R, Scheffer H, van Bokhoven H. Spectrum of p63 mutations in a selected patient cohort affected with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). Am J Med Genet A. 2009 Sep;149A(9):1948-51. doi: 10.1002/ajmg.a.32793. (
  • Rinne T, Brunner HG, van Bokhoven H. p63-associated disorders. Cell Cycle. 2007 Feb 1;6(3):262-8. Epub 2007 Feb 3. Review. (
  • Rinne T, Clements SE, Lamme E, Duijf PH, Bolat E, Meijer R, Scheffer H, Rosser E, Tan TY, McGrath JA, Schalkwijk J, Brunner HG, Zhou H, van Bokhoven H. A novel translation re-initiation mechanism for the p63 gene revealed by amino-terminal truncating mutations in Rapp-Hodgkin/Hay-Wells-like syndromes. Hum Mol Genet. 2008 Jul 1;17(13):1968-77. doi: 10.1093/hmg/ddn094. Epub 2008 Mar 25. (
  • van Bokhoven H, Hamel BC, Bamshad M, Sangiorgi E, Gurrieri F, Duijf PH, Vanmolkot KR, van Beusekom E, van Beersum SE, Celli J, Merkx GF, Tenconi R, Fryns JP, Verloes A, Newbury-Ecob RA, Raas-Rotschild A, Majewski F, Beemer FA, Janecke A, Chitayat D, Crisponi G, Kayserili H, Yates JR, Neri G, Brunner HG. p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. Am J Hum Genet. 2001 Sep;69(3):481-92. Epub 2001 Jul 17. (
  • Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dötsch V, Andrews NC, Caput D, McKeon F. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell. 1998 Sep;2(3):305-16. (


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? ( in the Handbook.

Reviewed: June 2011
Published: February 8, 2016