Reviewed November 2013
What is the official name of the OCRL gene?
The official name of this gene is “oculocerebrorenal syndrome of Lowe.”
OCRL is the gene's official symbol. The OCRL gene is also known by other names, listed below.
What is the normal function of the OCRL gene?
The OCRL gene provides instructions for making an enzyme that is present in cells throughout the body. This enzyme is part of a larger group of enzymes that modify fat (lipid) molecules known as membrane phospholipids. These molecules form the basic structure of cell membranes. Specifically, the OCRL enzyme regulates the levels of a membrane phospholipid called phosphatidylinositol 4,5-bisphosphate.
The OCRL enzyme 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 intended destinations inside or outside the cell. The OCRL enzyme is also found on endosomes, specialized compartments that are formed at the cell surface to carry proteins and other molecules to their destinations within the cell.
By controlling the level of phosphatidylinositol 4,5-bisphosphate, the OCRL enzyme helps regulate the transport of certain substances to and from the cell membrane and chemical signaling between cells. The enzyme may also be involved in the regulation of the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to move.
Recent research suggests that the OCRL enzyme is found in cell structures called primary cilia, which are microscopic, finger-like projections that stick out from the surface of cells and are involved in signaling pathways that transmit information between cells. Cilia are important for the structure and function of many types of cells, including cells in the brain, kidneys, and liver. Cilia are also necessary for the perception of sensory input (such as sight, hearing, and smell). Studies suggest that the OCRL enzyme may play a role in the formation, function, and maintenance of cilia.
How are changes in the OCRL gene related to health conditions?
- Dent disease - caused by mutations in the OCRL gene
At least 20 mutations in the OCRL gene have been found to cause Dent disease 2. This form of Dent disease is characterized by chronic kidney problems; some affected individuals also have mild intellectual disability, weak muscle tone (hypotonia), and clouding of the lens of the eyes (cataract) that does not impair vision. Some researchers consider Dent disease 2 to be a mild variant of Lowe syndrome, which is discussed below.
The OCRL gene mutations that cause Dent disease 2 reduce or eliminate the function of the OCRL enzyme. These changes impair the transport of certain molecules and regulation of the actin cytoskeleton. They may also affect cell signaling by altering the structure or function of cilia. Disruption of these important cell activities likely impairs kidney function, leading to excess protein in the urine (proteinuria), kidney stones, and ultimately kidney failure. It is unknown how loss of the OCRL enzyme contributes to the other signs and symptoms of this condition.
Because the OCRL enzyme 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 compensate for the defective OCRL enzyme in unaffected tissues.
- Lowe syndrome - caused by mutations in the OCRL gene
More than 120 mutations in the OCRL gene have been identified in individuals with Lowe syndrome, a condition that affects the eyes, brain, and kidneys. Some of these mutations prevent the production of any OCRL enzyme. Other mutations reduce or eliminate the activity of the enzyme or prevent it from interacting with other proteins within the cell. Researchers believe that the effects of these genetic changes are similar to those of the mutations that cause Dent disease 2: the mutations likely alter the transport of molecules within cells, regulation of the actin cytoskeleton, and the structure and function of cilia. It is unknown why some OCRL gene mutations cause Lowe syndrome and others cause Dent disease 2.
Because the OCRL enzyme is present throughout the body, it is unclear why Lowe syndrome primarily affects the kidney, brain, and eyes. As with Dent disease 2, it is possible that other enzymes may be able to compensate for the defective OCRL enzyme in unaffected tissues.
Where is the OCRL gene located?
Cytogenetic Location: Xq25
Molecular Location on the X chromosome: base pairs 129,532,740 to 129,592,556
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/4952))
The OCRL gene is located on the long (q) arm of the X chromosome at position 25.
More precisely, the OCRL gene is located from base pair 129,532,740 to base pair 129,592,556 on the X chromosome.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about OCRL?
You and your healthcare professional may find the following resources about OCRL helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth Edition, 2002): Transport into the Cell from the Plasma Membrane: Endocytosis (http://www.ncbi.nlm.nih.gov/books/NBK26870/)
- The Cell: A Molecular Approach (second edition, 2000): The Golgi Apparatus (http://www.ncbi.nlm.nih.gov/books/NBK9838/)
Gene Reviews - Clinical summary
- Gene Review: Dent Disease (http://www.ncbi.nlm.nih.gov/books/NBK99494)
- Gene Review: Lowe Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1480)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for OCRL (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4952%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28OCRL%5BTIAB%5D%29%20OR%20%28OCRL1%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%202880%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/300535)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_OCRL.html)
- HGNC Gene Family: Phosphoinositide phosphatases (http://www.genenames.org/cgi-bin/genefamilies/set/1079)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=8108)
- National Human Genome Research Institute: Lowe Syndrome Mutation Database (http://www.ncbi.nlm.nih.gov/lovd/home.php?select_db=OCRL)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4952)
What other names do people use for the OCRL gene or gene products?
- Lowe oculocerebrorenal syndrome protein
- phosphatidylinositol polyphosphate 5-phosphatase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding OCRL?
cell membrane ;
kidney stones ;
muscle tone ;
You may find definitions for these and many other terms in the Genetics Home Reference
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/1321346?dopt=Abstract)
- 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. Epub 2005 May 25. (http://www.ncbi.nlm.nih.gov/pubmed/15917292?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/22228094?dopt=Abstract)
- Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D, De Camilli P. A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway. Dev Cell. 2007 Sep;13(3):377-90. (http://www.ncbi.nlm.nih.gov/pubmed/17765681?dopt=Abstract)
- Hichri H, Rendu J, Monnier N, Coutton C, Dorseuil O, Poussou RV, Baujat G, Blanchard A, Nobili F, Ranchin B, Remesy M, Salomon R, Satre V, Lunardi J. From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. Hum Mutat. 2011 Apr;32(4):379-88. doi: 10.1002/humu.21391. Epub 2011 Mar 10. (http://www.ncbi.nlm.nih.gov/pubmed/21031565?dopt=Abstract)
- Hoopes RR Jr, Shrimpton AE, Knohl SJ, Hueber P, Hoppe B, Matyus J, Simckes A, Tasic V, Toenshoff B, Suchy SF, Nussbaum RL, Scheinman SJ. Dent Disease with mutations in OCRL1. Am J Hum Genet. 2005 Feb;76(2):260-7. Epub 2004 Dec 30. Erratum in: Am J Hum Genet. 2007 Sep;81(3):634. (http://www.ncbi.nlm.nih.gov/pubmed/15627218?dopt=Abstract)
- Hyvola N, Diao A, McKenzie E, Skippen A, Cockcroft S, Lowe M. Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. EMBO J. 2006 Aug 23;25(16):3750-61. Epub 2006 Aug 10. (http://www.ncbi.nlm.nih.gov/pubmed/16902405?dopt=Abstract)
- Lowe M. Structure and function of the Lowe syndrome protein OCRL1. Traffic. 2005 Sep;6(9):711-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16101675?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/22543976?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/18307981?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4952)
- Pirruccello M, De Camilli P. Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL. Trends Biochem Sci. 2012 Apr;37(4):134-43. doi: 10.1016/j.tibs.2012.01.002. Epub 2012 Feb 28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22381590?dopt=Abstract)
- Utsch B, Bökenkamp A, Benz MR, Besbas N, Dötsch J, Franke I, Fründ S, Gok F, Hoppe B, Karle S, Kuwertz-Bröking E, Laube G, Neb M, Nuutinen M, Ozaltin F, Rascher W, Ring T, Tasic V, van Wijk JA, Ludwig M. Novel OCRL1 mutations in patients with the phenotype of Dent disease. Am J Kidney Dis. 2006 Dec;48(6):942.e1-14. (http://www.ncbi.nlm.nih.gov/pubmed/17162149?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.