polycystic kidney disease More than 75 mutations in the PKD2 gene have been identified in people with polycystic kidney disease. These mutations are responsible for about 15 percent of all cases of autosomal dominant polycystic kidney disease (ADPKD), which is the most common type of this disorder. Mutations in the PKD2 gene include changes in single DNA building blocks (base pairs) and deletions or insertions of a small number of base pairs in the gene. Most PKD2 mutations are predicted to result in the production of an abnormally small, nonfunctional version of the polycystin-2 protein. Although researchers are uncertain how a lack of polycystin-2 leads to the formation of cysts, it likely disrupts the protein's interaction with polycystin-1 and alters signaling within the cell and in primary cilia. As a result, cells lining the renal tubules may grow and divide abnormally, leading to the growth of numerous cysts characteristic of polycystic kidney disease.

     The PKD2 gene provides instructions for making a protein called polycystin-2. This protein is found in the kidneys before birth and in many adult tissues. Although its exact function is not well understood, polycystin-2 can be regulated by a larger, somewhat similar protein called polycystin-1. Polycystin-2 likely functions as a channel spanning the cell membrane of kidney cells. In conjunction with polycystin-1, the channel transports positively charged atoms (ions), particularly calcium ions, into the cell. This influx of calcium ions triggers a cascade of chemical reactions inside the cell that may instruct the cell to undergo certain changes, such as maturing to take on specialized functions. Polycystin-1 and polycystin-2 likely work together to help regulate cell growth and division (proliferation), cell movement (migration), and interactions with other cells. Polycystin-2 is also active in other parts of the cell, including cellular structures called primary cilia. Primary cilia are tiny, fingerlike projections that line the small tubes where urine is formed (renal tubules). Researchers believe that primary cilia sense the movement of fluid through these tubules, which appears to help maintain the tubules' size and structure. The interaction of polycystin-1 and polycystin-2 in renal tubules promotes the normal development and function of the kidneys.

The following transcription factors affect gene expression:

• NF-kappaB
• AP-1
• c-Jun
• NF-kappaB1

Tissue specificity:

Strongly expressed in ovary, fetal and adult kidney, testis, and small intestine. Not detected in peripheral leukocytes.

Molecular Function:

• Actinin Binding
• Atpase Binding
• Calcium-Induced Calcium Release Activity
• Calcium Ion Binding
• Cytoskeletal Protein Binding
• Hlh Domain Binding
• Identical Protein Binding
• Ion Channel Binding
• Phosphoprotein Binding
• Potassium Channel Activity
• Protein Homodimerization Activity
• Receptor Binding
• Voltage-Gated Calcium Channel Activity
• Voltage-Gated Cation Channel Activity
• Voltage-Gated Ion Channel Activity
• Voltage-Gated Sodium Channel Activity

Biological Processes:

• Aorta Development
• Branching Involved In Ureteric Bud Morphogenesis
• Calcium Ion Transmembrane Transport
• Calcium Ion Transport
• Cell Cycle Arrest
• Cellular Response To Fluid Shear Stress
• Cellular Response To Hydrostatic Pressure
• Cellular Response To Osmotic Stress
• Cellular Response To Reactive Oxygen Species
• Centrosome Duplication
• Cytoplasmic Sequestering Of Transcription Factor
• Detection Of Mechanical Stimulus
• Detection Of Nodal Flow
• Determination Of Left/Right Symmetry
• Determination Of Liver Left/Right Asymmetry
• Embryonic Placenta Development
• Heart Development
• Heart Looping
• Jak-Stat Cascade
• Liver Development
• Mesonephric Duct Development
• Mesonephric Tubule Development
• Metanephric Ascending Thin Limb Development
• Metanephric Cortex Development
• Metanephric Cortical Collecting Duct Development
• Metanephric Distal Tubule Development
• Metanephric Mesenchyme Development
• Metanephric Part Of Ureteric Bud Development
• Metanephric Smooth Muscle Tissue Development
• Metanephric S-Shaped Body Morphogenesis
• Negative Regulation Of Cell Proliferation
• Negative Regulation Of G1/S Transition Of Mitotic Cell Cycle
• Negative Regulation Of Ryanodine-Sensitive Calcium-Release Channel Activity
• Neural Tube Development
• Placenta Blood Vessel Development
• Positive Regulation Of Cell Cycle Arrest
• Positive Regulation Of Cyclin-Dependent Protein Serine/Threonine Kinase Activity Involved In G1/S Transition Of Mitotic Cell Cycle
• Positive Regulation Of Inositol 1,4,5-Trisphosphate-Sensitive Calcium-Release Channel Activity
• Positive Regulation Of Nitric Oxide Biosynthetic Process
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Regulation Of Calcium Ion Import
• Regulation Of Camp Metabolic Process
• Regulation Of Cell Proliferation
• Release Of Sequestered Calcium Ion Into Cytosol
• Renal Artery Morphogenesis
• Renal Tubule Morphogenesis
• Sodium Ion Transmembrane Transport
• Spinal Cord Development