Paired-like homeobox protein 2B (PHOX2B)

Paired-like homeobox protein 2B (PHOX2B) is a transcription factor exclusively expressed in the nervous system, critical for the differentiation and survival of sympathetic neurons and chromaffin cells. It determines the neurotransmitter phenotype of noradrenergic neurons, such as those in the locus coeruleus, by acting as a DNA-binding regulator for various gene promoters and response elements. Mutations—especially polyalanine tract expansions—cause congenital central hypoventilation syndrome, and other pathogenic variants predispose to Hirschsprung's disease, neuroblastoma, and ROHHAD. PHOX2B is a highly sensitive and specific marker for detecting neuroblastoma via immunohistochemistry, particularly useful in challenging diagnostic scenarios. Although not a direct drug target, it is essential in disease mechanisms and considered a therapeutic target in gene-based approaches and in the context of cancer predisposition.

Other names

Neuroblastoma PhoxNBPhoxPaired mesoderm homeobox protein 2BPMX2B

Not directly targeted by drugs; its dysfunction due to mutations affects other downstream targets.