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NK2 homeobox gene cluster: Functions and roles in human diseases

Genes & Diseases 2023年第5期10卷 2038-2048页

作者： catia mio Federica Baldan Giuseppe Damante Dipartimento di Area Medica Universitàdegli Studi di UdineUdine 33100Italy Istituto di Genetica Medica Azienda Sanitaria Universitaria Friuli CentraleUdine 33100Italy

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.

关键词： Drosophila melanogaster Evolutionary conservation Homeobox Homeotic genes NK2 genes

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