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OCRL gene
URL of this page: https://medlineplus.gov/genetics/gene/ocrl/

OCRL gene

OCRL inositol polyphosphate-5-phosphatase

Normal Function

The OCRL gene provides instructions for making the enzyme OCRL, which is present in cells throughout the body. OCRL is part of a larger group of enzymes that modify fat (lipid) molecules known as membrane phospholipids. Phospholipids help form the basic structure of cell membranes.

OCRL is found in several areas within cells. It is concentrated in a complex network of membranes known as the trans-Golgi network, which sorts proteins and other molecules and sends them to their proper locations. OCRL is also found in endosomes, specialized compartments that help transport proteins and other molecules within the cell. The trans-Golgi network and endosomes play an important role in endocytosis, which is the process of transporting proteins from the outer cell membrane to the inside of the cell. 

Endocytosis is especially important in proximal tubular cells. Proximal tubules are structures that are found in the kidneys. They help reabsorb proteins and other nutrients into the bloodstream. OCRL plays a key role in the kidneys' ability to reabsorb proteins and important nutrients.

Recent research suggests that OCRL is also involved in the formation of certain types of cilia. Cilia are microscopic, finger-like projections that stick out from the surface of cells. They are important for the structure and function of many types of cells, including cells in the eyes and kidneys.

Health Conditions Related to Genetic Changes

Dent disease

Changes in the OCRL gene can cause a type of Dent disease called Dent disease 2. Genetic changes that cause disease are called pathogenic variants. Dent disease 2 occurs almost exclusively in males, and affected individuals have chronic kidney disease that can lead to kidney failure. Some affected individuals also have developmental delays, mild intellectual disabilities, and a clouding of the lens of the eye (cataract) that typically does not cause significant visual impairment. Some researchers consider Dent disease 2 to be a mild version of Lowe syndrome, which is discussed below.

Pathogenic variants in the OCRL gene cause cells to produce a version of the enzyme that does not function properly. These changes likely disrupt endocytosis, which impairs the reabsorption of proteins in the proximal tubules of the kidneys. The loss of functional OCRL may also affect cell signaling by altering the structure or function of cilia. Disruption of these important cell processes impairs kidney function, leading to the loss of proteins in the urine (proteinuria) and the chronic kidney disease that is seen in people with Dent disease 2.

Because OCRL is present throughout the body, it is unclear why Dent disease 2 primarily affects the kidneys and, to a lesser extent, the brain, eyes, and other tissues. It is possible that other enzymes may be able to make up for OCRL’s reduced function in unaffected tissues.

More About This Health Condition

Lowe syndrome

Pathogenic variants in the OCRL gene can also cause Lowe syndrome, a condition that affects the eyes, brain, and kidneys. As with Dent disease 2, Lowe syndrome occurs almost exclusively in males.

Some of the pathogenic variants that are associated with Lowe syndrome cause cells to make a version of the enzyme that does not function properly, while others prevent the production of any functional enzyme. These changes appear to impair endocytosis and the structure and function of cilia. It is unknown why some OCRL gene variants cause Lowe syndrome and others cause Dent disease 2.

It is also unclear why Lowe syndrome primarily affects the kidney, brain, and eyes. It is possible that other enzymes may be able to make up for OCRL’s reduced function in other tissues.

More About This Health Condition

Other Names for This Gene

  • Dent disease 2
  • Dent-2
  • OCRL1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Attree O, Olivos IM, Okabe I, Bailey LC, Nelson DL, Lewis RA, McInnes RR, Nussbaum RL. The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Nature. 1992 Jul 16;358(6383):239-42. doi: 10.1038/358239a0. Citation on PubMed
  • Choudhury R, Diao A, Zhang F, Eisenberg E, Saint-Pol A, Williams C, Konstantakopoulos A, Lucocq J, Johannes L, Rabouille C, Greene LE, Lowe M. Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network. Mol Biol Cell. 2005 Aug;16(8):3467-79. doi: 10.1091/mbc.e05-02-0120. Epub 2005 May 25. Citation on PubMed or Free article on PubMed Central
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  • Coon BG, Hernandez V, Madhivanan K, Mukherjee D, Hanna CB, Barinaga-Rementeria Ramirez I, Lowe M, Beales PL, Aguilar RC. The Lowe syndrome protein OCRL1 is involved in primary cilia assembly. Hum Mol Genet. 2012 Apr 15;21(8):1835-47. doi: 10.1093/hmg/ddr615. Epub 2012 Jan 6. Citation on PubMed
  • Ehlayel AM, Copelovitch L. Update on Dent Disease. Pediatr Clin North Am. 2019 Feb;66(1):169-178. doi: 10.1016/j.pcl.2018.09.003. Citation on PubMed
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  • Hall AM, Polesel M, Berquez M. The proximal tubule, protein uptake, and the riddle of the segments. Kidney Int. 2021 Apr;99(4):803-805. doi: 10.1016/j.kint.2020.12.031. Citation on PubMed
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  • Luo N, West CC, Murga-Zamalloa CA, Sun L, Anderson RM, Wells CD, Weinreb RN, Travers JB, Khanna H, Sun Y. OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Hum Mol Genet. 2012 Aug 1;21(15):3333-44. doi: 10.1093/hmg/dds163. Epub 2012 Apr 27. Citation on PubMed or Free article on PubMed Central
  • McCrea HJ, Paradise S, Tomasini L, Addis M, Melis MA, De Matteis MA, De Camilli P. All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding. Biochem Biophys Res Commun. 2008 May 2;369(2):493-9. doi: 10.1016/j.bbrc.2008.02.067. Epub 2008 Feb 26. Citation on PubMed or Free article on PubMed Central
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