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:

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

Biological Processes:

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