The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein

Related Experiment Video

Updated: Oct 2, 2026

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

Christopher J Ward1, Marie C Hogan, Sandro Rossetti

  • 1Division of Nephrology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.

Nature Genetics
|March 29, 2002
PubMed

Insights

Researchers identified the PKHD1 gene as a cause of autosomal recessive polycystic kidney disease (ARPKD). This discovery sheds light on the genetic basis of ARPKD, a serious kidney and liver disorder.

Area of Science:

  • Genetics
  • Molecular Biology
  • Pediatric Nephrology

Background:

  • Autosomal recessive polycystic kidney disease (ARPKD) is a significant genetic disorder causing kidney and liver dysfunction.
  • It is characterized by collecting duct dilation and biliary dysgenesis, leading to substantial morbidity and mortality.

Purpose of the Study:

  • To identify the genetic cause of ARPKD.
  • To characterize the PKHD1 gene and its encoded protein, fibrocystin, in relation to ARPKD pathogenesis.

Main Methods:

  • Genetic analysis of a rat model with recessive polycystic kidney disease.
  • Screening of the human ortholog gene, PKHD1, in ARPKD patients.
  • Characterization of PKHD1 transcript and protein expression.

Main Results:

  • An orthologous relationship was established between the rat locus and the human ARPKD region.
  • Mutations in PKHD1 were identified in ARPKD probands, including truncating and missense variants.
  • PKHD1 encodes a large protein, fibrocystin, expressed in kidney, liver, and pancreas.

Conclusions:

  • PKHD1 is the causative gene for ARPKD.
  • Fibrocystin, the protein product of PKHD1, is likely involved in collecting duct and biliary differentiation.
  • This finding provides a molecular basis for understanding ARPKD and potential therapeutic targets.

More Related Videos

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring07:35

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Published on: June 23, 2015

Evaluation of Zebrafish Kidney Function Using a Fluorescent Clearance Assay08:13

Evaluation of Zebrafish Kidney Function Using a Fluorescent Clearance Assay

Published on: February 20, 2015

Related Concept Videos

Renal Corpuscle01:20

Renal Corpuscle

The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous capillaries...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Nephrons01:10

Nephrons

The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma happens...
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...