NKX2-5

Description

The NKX2-5 (NK2 homeobox 5) is a protein-coding gene located on chromosome 5.

NKX2-5 is a protein encoded by the NKX2-5 gene in humans. Homeobox-containing genes, like NKX2-5, play vital roles in regulating tissue-specific gene expression, essential for tissue differentiation and determining developmental patterns. NKX2-5 is crucial for the development of the heart, including atrial, ventricular, and conotruncal septation, atrioventricular (AV) valve formation, and maintaining AV conduction. Mutations in NKX2-5 expression are linked to congenital heart disease (CHD) and related conditions. Patients with NKX2-5 mutations often exhibit AV conduction block and atrial septal defects (ASD). Recent research has explored the postnatal roles of cardiac transcription factors like NKX2-5.

NKX2-5 is a transcription factor essential for the development of the heart and the spleen. It activates transcription of NPPA/ANF during heart development in cooperation with GATA4. NKX2-5 may also cooperate with TBX2 to negatively regulate NPPA/ANF expression in the atrioventricular canal. It binds to the core DNA motif of the NPPA promoter and, along with PBX1, is required for spleen development through a mechanism involving CDKN2B repression. NKX2-5 positively regulates the transcription of genes such as COL3A1 and MMP2, leading to increased pulmonary endothelial fibrosis in response to hypoxia.

NKX2-5 is also known as CHNG5, CSX, CSX1, HLHS2, NKX2.5, NKX2E, NKX4-1, VSD3.

Associated Diseases

• Familial bicuspid aortic valve
• Atrial septal defect-atrioventricular conduction defects syndrome
• Atrial septal defect with atrioventricular conduction defects
• Thyroid ectopia
• Athyreosis
• Familial atrial fibrillation
• Ventricular septal defect 3
• Hypoplastic left heart syndrome
• Hypoplastic left heart syndrome 2
• Hypothyroidism, congenital, nongoitrous, 5
• Conotruncal heart malformations
• Familial progressive cardiac conduction defect
• Atrial septal defect, ostium secundum type
• Tetralogy of Fallot