From the Guidelines
The PAX2 gene plays a crucial role in kidney development and disease, and its naming is essential for unified disease terminology, as seen in the example of PAX2-kidney disease. The PAX2 gene is a critical developmental gene that encodes a transcription factor essential for kidney, eye, ear, and central nervous system formation during embryonic development 1. It belongs to the paired box (PAX) family of genes that regulate tissue development and cellular differentiation. Some key points about the PAX2 gene include:
- It is particularly important in the formation of the renal system, where it controls the conversion of mesenchymal cells into epithelial structures during kidney development
- Mutations in the PAX2 gene are associated with renal coloboma syndrome (also known as papillorenal syndrome), characterized by kidney abnormalities and optic nerve malformations
- In adults, PAX2 expression is normally downregulated, but its reactivation has been observed in several cancers, including renal cell carcinoma, ovarian, and endometrial cancers, suggesting its potential role in tumor development
- The gene is located on chromosome 10q24.31 in humans and contains 12 exons The use of a two-part naming approach, such as PAX2-kidney disease, provides flexibility and clarity in disease terminology, as discussed in the Kidney International study 1. Understanding PAX2's function has implications for developmental biology, congenital disorders, and potentially for targeted cancer therapies that might modulate its expression or activity.
Some of the key considerations for the role of the PAX2 gene in disease include:
- The importance of unified disease terminology in accurately describing and studying genetic diseases
- The potential for PAX2 mutations to cause a range of kidney and other developmental abnormalities
- The need for further research into the role of PAX2 in cancer development and progression
- The potential for targeted therapies to modulate PAX2 expression or activity in the treatment of cancer and other diseases.
From the Research
Role of PAX2 Gene
The PAX2 gene plays a crucial role in various developmental processes, including:
- Kidney development: PAX2 is essential for the development of the kidneys, and its mutation can lead to renal coloboma syndrome (RCS) 2, 3, 4.
- Urogenital tract development: PAX2 is involved in the development of the urogenital tract 3, 4.
- Eye development: PAX2 mutations can cause optic nerve colobomas, a characteristic feature of RCS 3, 5, 6.
- Ear and central nervous system development: PAX2 is also involved in the development of the ears and central nervous system 3, 4.
PAX2-Related Disorders
PAX2 mutations are associated with various disorders, including:
- Renal coloboma syndrome (RCS): a rare autosomal dominant syndrome characterized by optic nerve colobomas and renal anomalies 2, 3, 5, 6.
- Isolated renal hypoplasia: PAX2 mutations can cause isolated renal hypoplasia, a condition characterized by underdeveloped kidneys 3.
- Alport-like glomerular basement membrane changes: PAX2 mutations can lead to abnormal glomerular basement membrane structure, similar to Alport syndrome 5.
- Hyperuricemia: PAX2 mutations can cause hyperuricemia, a condition characterized by elevated uric acid levels in the blood 6.
PAX2 Function
PAX2 is a transcription factor that interacts with other important transcription factors to regulate kidney development and disease 4. It is expressed in the nephric duct, mesenchyme of pronephrons, mesonephrons, and metanephrons, and plays a critical role in:
- Nephric lineage specification
- Pro/mesonephric tubule formation and descent
- Emergence of the ureteric bud
- Branching morphogenesis
- Nephron induction 4