NK2 genes (

NKX2

gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications

vertebrate

NKX2

genes are classified into two distinct families

NK2.1

and

NK2.2

. The former is constituted by

NKX2-1

and

NKX2-4

genes

which are homologous to the

Drosophila scro

gene; the latter includes

NKX2-2

and

NKX2-8

genes

which are homologous to the

Drosophila vnd

gene. Conservation of these genes is not only related to molecular structure and expression

but also to biological functions. In

Drosophila

and vertebrates

NK2 genes share roles in the development of ventral regions of the central nervous system. In vertebrates

NKX2

genes have a relevant role in the development of several other organs such as the thyroid

lung

and pancreas. Loss-of-function mutations in

NKX2-1

and

NKX2-2

are the monogenic cause of the brain-lung-thyroid syndrome and neonatal diabetes

respectively. Alterations in

NKX2-4

and

NKX2-8

genes may play a role in multifactorial diseases

autism spectrum disorder

and neural tube defects

respectively.

NKX2-1

NKX2-2

and

NKX2-8

are expressed in various cancer types as either oncogenes or tumor suppressor genes. Several data indicate that evaluation of their expression in tumors has diagnostic and/or prognostic value.