PHOX2B gene encodes a highly conserved transcription factor, which promotes the formation of neurons and regulates nerve cells differentiation during the early development phase. PHOX2B protein is active in the neural crest - a group of cells in the early embryo that give rise to many tissues and organs. These cells migrate to form parts of the autonomic nervous system that control body functions such as breathing, blood pressure, heart rate, and digestion.

Defects in the PHOX2B gene cause congenital central hypoventilation syndrome (CCHS). Approximately 90% of CCHS patients are heterozygous for the polyalanine repeat expansion mutation in exon 3 of the PHOX2B gene. These mutations are in-frame and range from 15 to 39 nucleotide insertions, and result in expansion of the normal 20-repeat polyalanine tract to 25 to 33 alanine repeats.