TP63 Gene

The TP63 gene, a protein-coding gene, is located on chromosome 3q28 and encodes TP63 (tumor protein P63), a member of the p53 family of transcription factors to which p63 and p73 also belong (Levrero Met al. 2000).

The functional domains of p53 family proteins include an N-terminal transactivation domain, a central DNA-binding domain, and an oligomerization domain. Alternative splicing of this gene and use of alternative promoters results in multiple transcript variants encoding different isoforms that differ in their functional properties (Gonfloni S et al. 2015). These isoforms play roles in skin development and maintenance, adult stem/progenitor cell regulation, cardiac development, and premature aging.

Some isoforms have been found to protect the germline by eliminating oocytes or testicular germ cells that have suffered DNA damage.

Mutations in this gene are associated with the following disorders (Rinne T et al. 2007):

• EEC syndrome 3 (ectodermal dysplasia and cleft lip and palate syndrome 3).
• Cleft palate malformation (SHFM4)
• Ankyloblepharon-ectodermal defects-lip-jaw- palate cleft syndrome
• ADULT syndrome (acro-dermato-ungual-lacrimal-tooth), limb-mammary syndrome
• Rap-Hodgkin syndrome (RHS)
• Orofacial cleft 8.

Related pathways include TP53 regulates transcription of cell death genes and regulation of TP53 activity. An important paralog of this gene is TP63 and TP73.

1. Gonfloni S et al (2015) P63 in health and cancer. Int J Dev Biol 59: 87-93.
2. Levrero Met al.(2000) The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci 113:1661-1670.
3. Rinne T et al (2007) p63-associated disorders. Cell Cycle 6:262-268.