PKD1

PKD1, also known as polycystic kidney disease 1, is a gene on chromosome 16p13.3 that encodes polycystin-1, a large transmembrane protein expressed in renal tubular epithelium. Polycystin-1 participates in cell–cell and cell–matrix interactions and, with polycystin-2 (PKD2), regulates calcium signaling. The two proteins form a complex in primary cilia and at the plasma membrane, suspected to sense mechanical stimuli and coordinate tubular morphogenesis.

Mutations in PKD1 cause autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disorder. PKD1 mutations account for the majority of ADPKD cases (roughly 60–85%, with PKD2 accounting for most of the remainder). Affected individuals develop bilateral renal cysts that enlarge over time, causing progressive kidney dysfunction. PKD1-associated disease tends to present earlier and be more severe than PKD2-related disease.

PKD1 is among the largest human genes. Its sequence includes six pseudogenes on chromosome 16 with high homology, which complicate genetic testing and require specialized methods for accurate mutation detection.

Diagnosis relies on imaging and family history; ultrasound or MRI shows multiple bilateral renal cysts, typically with age. Extrarenal manifestations may include hepatic cysts, pancreatic cysts, intracranial aneurysms, and other vascular abnormalities. Genetic testing can confirm PKD1 mutations and guide family counseling.

Management aims to slow progression and treat complications. Blood pressure control and pain management are standard; vasopressin V2 receptor antagonists such as tolvaptan can slow eGFR decline in adults with ADPKD from PKD1 or PKD2 mutations. There is no cure.