PKD1 gene

The PKD1 gene provides instructions for the polycystin-1 protein, which is essential for kidney development and function; mutations in this gene are the primary cause of autosomal dominant polycystic kidney disease.

Normal Function

The PKD1 gene provides instructions for making a protein called polycystin-1. This protein is most active in kidney cells before birth; much less of the protein is made in normal adult kidneys. Although its exact function is not well understood, polycystin-1 appears to interact with a smaller, somewhat similar protein called polycystin-2.

Polycystin-1 spans the cell membrane of kidney cells, allowing it to interact with other proteins, carbohydrates, and fat molecules (lipids) outside the cell to receive signals that help the cell respond to its environment. When a molecule binds to polycystin-1, the protein interacts with polycystin-2 to trigger a cascade of chemical reactions inside the cell. These reactions instruct the cell to undergo changes, such as maturing to take on specialized functions. Polycystin-1 and polycystin-2 likely work together to help regulate cell growth, division (proliferation), cell movement (migration), and interactions with other cells.

Polycystin-1 is also found in cell structures called primary cilia—tiny, fingerlike projections that line the renal tubules where urine is formed. Researchers believe that primary cilia sense the movement of fluid through these tubules, which helps 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.

Health Conditions Related to Genetic Changes

Polycystic kidney disease

More than 250 mutations in the PKD1 gene have been identified in people with polycystic kidney disease. These mutations are responsible for about 85 percent of cases of autosomal dominant polycystic kidney disease (ADPKD), which is the most common type of this disorder.

Mutations in the PKD1 gene include deletions or insertions of DNA building blocks (base pairs) and alterations of one or more base pairs. Most PKD1 mutations are predicted to produce an abnormally small, nonfunctional version of the polycystin-1 protein. Although researchers are uncertain how a lack of polycystin-1 leads to the formation of cysts, it probably disrupts the protein's signaling function 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.

Other Names for This Gene

• Lov-1
• PBP
• Pc-1
• PC1
• PKD1_HUMAN
• polycystic kidney disease 1 (autosomal dominant)
• polycystin-1
• TRPP1