PKHD1

PKHD1 is the gene that encodes fibrocystin, also known as polyductin (FPC). It is best known for its role in autosomal recessive polycystic kidney disease (ARPKD) and related fibropolycystic liver diseases. Mutations in PKHD1 disrupt the function of fibrocystin, leading to dilatation of renal collecting ducts and congenital hepatic fibrosis.

The gene is expressed in epithelial cells of the kidney and biliary tree and encodes a large, single-pass transmembrane protein that localizes to primary cilia and other membranes. The extracellular domain is thought to participate in cell–cell signaling and tubule morphogenesis, while the intracellular tail participates in signaling networks.

In the kidney, fibrocystin interacts with other ciliary proteins in maintaining tubular architecture; loss of function leads to cyst formation and progressive kidney dysfunction.

ARPKD is inherited in an autosomal recessive pattern; affected individuals typically present in infancy or early childhood with enlarged, echogenic kidneys detectable by ultrasound, poor corticomedullary differentiation, and hypertension. Hepatic involvement often manifests as congenital hepatic fibrosis, contributing to portal hypertension and liver dysfunction. Genotype-phenotype correlations are incomplete; many PKHD1 variants have been reported.

Genetic testing for PKHD1 mutations confirms diagnosis, informs family planning, and guides management. Ongoing research investigates fibrocystin's role in ciliary signaling and ductal morphogenesis, and how modifier genes influence disease severity.