The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

OCRL  -  oculocerebrorenal syndrome of Lowe

Homo sapiens

Synonyms: INPP5F, Inositol polyphosphate 5-phosphatase OCRL-1, LOCR, Lowe oculocerebrorenal syndrome protein, NPHL2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of OCRL


Psychiatry related information on OCRL

  • Five of these 12 behaviors, i.e., temper tantrums, irritability, complex repetitive behaviors (stereotypy)/mannerisms, obsessions/unusual preoccupations, and negativism, were identified by discriminant function analysis to significantly distinguish between controls and OCRL individuals [6].
  • Individuals with OCRL displayed significantly more severe maladaptive behaviors than control boys, as measured by the Vineland Adaptive Behavior Scales (VABS), with 41% of the difference between the two groups attributable to the diagnosis of OCRL [6].

High impact information on OCRL

  • Lowe's oculocerebrorenal syndrome (OCRL) is a human X-linked developmental disorder of unknown pathogenesis and has a pleiotropic phenotype affecting the lens, brain and kidneys [7].
  • Our results suggest that OCRL may be an inborn error of inositol phosphate metabolism [7].
  • Here we use yeast artificial chromosomes with inserts that span the X chromosomal breakpoint from a female OCRL patient in order to isolate complementary DNAs for a gene that is interrupted by the translocation [7].
  • Surprisingly, mice deficient in Ocrl1 do not develop the congenital cataracts, renal Fanconi syndrome, or neurological abnormalities seen in the human disorder [1].
  • We have used targeted disruption in embryonic stem cells to make mice deficient in Ocrl1, the mouse homologue for OCRL1, as an animal model for the disease [1].

Chemical compound and disease context of OCRL


Biological context of OCRL

  • The translocation chromosome originated from an unaffected male without a visible translocation, indicating that the most likely cause of OCRL in this patient is the de novo translocation that disrupted the OCRL locus [10].
  • The predicted amino acid sequence of the OCRL gene, OCRL-1, was used to develop antibodies against the OCRL-1 protein [11].
  • The OCRL medical literature reports the frequency of glaucoma, secondary clinical signs of increased intraocular pressure (IOP), and results of glaucoma surgery, but little information related to the responsible filtration angle abnormalities [12].
  • A pair of yeast artificial chromosomes (YACs) that span the Xq25-q26 translocation breakpoint in a female with OCRL were used as probes to screen cDNA libraries made from bovine lens and human kidney [13].
  • All patients had markedly reduced PtdIns(4,5)P2 5-phosphatase activity in their fibroblasts, whereas the ocrl1 protein was detectable by immunoblotting in some patients with either missense mutations or a codon deletion but was not detectable in those with premature termination mutations [2].

Anatomical context of OCRL


Associations of OCRL with chemical compounds

  • These results suggest that OCRL is mainly a lipid phosphatase that may control cellular levels of a critical metabolite, phosphatidylinositol 4,5-bisphosphate [16].
  • Despite the atypical renal findings, skin fibroblast analysis for PtdIns (4,5)P2 5-phosphatase was performed, and enzyme activity was low, consistent with the diagnosis of OCRL [17].
  • This suggests that Ocrl1 is active as a PIP2 5-phosphatase in Rac induced membrane ruffles [9].
  • In this study we defined the localization of ocrl1 in fibroblasts and in two kidney epithelial cell lines by three methods: immunofluorescence, subcellular fractionation, and a dynamic perturbation assay with brefeldin A [18].
  • Isolated nephron-segment RT-PCR showed that OCRL-1 is expressed in all segments studied: the glomerulus, proximal tubule, medullary and cortical thick ascending limb, distal convoluted tubule, connecting tubule, cortical collecting duct, and outer medullary collecting duct [19].

Physical interactions of OCRL


Other interactions of OCRL


Analytical, diagnostic and therapeutic context of OCRL

  • We analyzed the gene in two Japanese OCRL patients and their families by DNA sequencing and mismatch polymerase chain reaction (PCR) followed by restriction digestion [23].
  • We are using the approaches of linkage analysis, mapping with somatic cell hybrids, and long-range restriction mapping to determine the order of Xq24-q26 markers with respect to each other and to the OCRL locus [24].
  • CONCLUSION: A primary X-linked infantile glaucoma is a defining and frequent component of OCRL and is secondary to expression of a primary filtration angle anomaly [12].
  • This paper presents a new method that should be an easy and helpful tool for diagnosing OCRL and that contributes a new aspect of this syndrome through in situ hybridization histochemical staining of normal fetal tissues [25].
  • Western blot analysis showed absence or severe decrease in OCRL-1 protein in cell lysates derived from these patients [26].


  1. Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice. Jänne, P.A., Suchy, S.F., Bernard, D., MacDonald, M., Crawley, J., Grinberg, A., Wynshaw-Boris, A., Westphal, H., Nussbaum, R.L. J. Clin. Invest. (1998) [Pubmed]
  2. Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome. Lin, T., Orrison, B.M., Leahey, A.M., Suchy, S.F., Bernard, D.J., Lewis, R.A., Nussbaum, R.L. Am. J. Hum. Genet. (1997) [Pubmed]
  3. Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network. Faucherre, A., Desbois, P., Satre, V., Lunardi, J., Dorseuil, O., Gacon, G. Hum. Mol. Genet. (2003) [Pubmed]
  4. Carrier assessment in families with lowe oculocerebrorenal syndrome: novel mutations in the OCRL1 gene and correlation of direct DNA diagnosis with ocular examination. Röschinger, W., Muntau, A.C., Rudolph, G., Roscher, A.A., Kammerer, S. Mol. Genet. Metab. (2000) [Pubmed]
  5. Two families of Lowe oculocerebrorenal syndrome with elevated serum HDL cholesterol levels and CETP gene mutation. Asami, T., Inano, K., Miida, T., Kikuchi, T., Uchiyama, M. Acta Paediatr. (1997) [Pubmed]
  6. Evidence for a discrete behavioral phenotype in the oculocerebrorenal syndrome of Lowe. Kenworthy, L., Charnas, L. Am. J. Med. Genet. (1995) [Pubmed]
  7. The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Attree, O., Olivos, I.M., Okabe, I., Bailey, L.C., Nelson, D.L., Lewis, R.A., McInnes, R.R., Nussbaum, R.L. Nature (1992) [Pubmed]
  8. Cell lines from kidney proximal tubules of a patient with Lowe syndrome lack OCRL inositol polyphosphate 5-phosphatase and accumulate phosphatidylinositol 4,5-bisphosphate. Zhang, X., Hartz, P.A., Philip, E., Racusen, L.C., Majerus, P.W. J. Biol. Chem. (1998) [Pubmed]
  9. Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology. Faucherre, A., Desbois, P., Nagano, F., Satre, V., Lunardi, J., Gacon, G., Dorseuil, O. Hum. Mol. Genet. (2005) [Pubmed]
  10. Lowe oculocerebrorenal syndrome in a female with a balanced X;20 translocation: mapping of the X chromosome breakpoint. Mueller, O.T., Hartsfield, J.K., Gallardo, L.A., Essig, Y.P., Miller, K.L., Papenhausen, P.R., Tedesco, T.A. Am. J. Hum. Genet. (1991) [Pubmed]
  11. The oculocerebrorenal syndrome gene product is a 105-kD protein localized to the Golgi complex. Olivos-Glander, I.M., Jänne, P.A., Nussbaum, R.L. Am. J. Hum. Genet. (1995) [Pubmed]
  12. Glaucoma with the oculocerebrorenal syndrome of Lowe. Walton, D.S., Katsavounidou, G., Lowe, C.U. Journal of glaucoma. (2005) [Pubmed]
  13. Isolation of cDNA sequences around the chromosomal breakpoint in a female with Lowe syndrome by direct screening of cDNA libraries with yeast artificial chromosomes. Okabe, I., Attree, O., Bailey, L.C., Nelson, D.L., Nussbaum, R.L. J. Inherit. Metab. Dis. (1992) [Pubmed]
  14. Physical mapping and genomic structure of the Lowe syndrome gene OCRL1. Nussbaum, R.L., Orrison, B.M., Jänne, P.A., Charnas, L., Chinault, A.C. Hum. Genet. (1997) [Pubmed]
  15. A novel domain suggests a ciliary function for ASPM, a brain size determining gene. Ponting, C.P. Bioinformatics (2006) [Pubmed]
  16. The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase. Zhang, X., Jefferson, A.B., Auethavekiat, V., Majerus, P.W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  17. Unusual renal features of Lowe syndrome in a mildly affected boy. Gropman, A., Levin, S., Yao, L., Lin, T., Suchy, S., Sabnis, S., Hadley, D., Nussbaum, R. Am. J. Med. Genet. (2000) [Pubmed]
  18. Ocrl1, a PtdIns(4,5)P(2) 5-phosphatase, is localized to the trans-Golgi network of fibroblasts and epithelial cells. Dressman, M.A., Olivos-Glander, I.M., Nussbaum, R.L., Suchy, S.F. J. Histochem. Cytochem. (2000) [Pubmed]
  19. cDNA cloning and localization of OCRL-1 in rabbit kidney. Erb, B.C., Velázquez, H., Gisser, M., Shugrue, C.A., Reilly, R.F. Am. J. Physiol. (1997) [Pubmed]
  20. Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network. Choudhury, R., Diao, A., Zhang, F., Eisenberg, E., Saint-Pol, A., Williams, C., Konstantakopoulos, A., Lucocq, J., Johannes, L., Rabouille, C., Greene, L.E., Lowe, M. Mol. Biol. Cell (2005) [Pubmed]
  21. Tightly linked flanking markers for the Lowe oculocerebrorenal syndrome, with application to carrier assessment. Reilly, D.S., Lewis, R.A., Ledbetter, D.H., Nussbaum, R.L. Am. J. Hum. Genet. (1988) [Pubmed]
  22. Lowe syndrome, a deficiency of phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus. Suchy, S.F., Olivos-Glander, I.M., Nussabaum, R.L. Hum. Mol. Genet. (1995) [Pubmed]
  23. Identification of two novel mutations in the OCRL1 gene in Japanese families with Lowe syndrome. Kubota, T., Sakurai, A., Arakawa, K., Shimazu, M., Wakui, K., Furihata, K., Fukushima, Y. Clin. Genet. (1998) [Pubmed]
  24. Genetic and physical mapping of Xq24-q26 markers flanking the Lowe oculocerebrorenal syndrome. Reilly, D.S., Lewis, R.A., Nussbaum, R.L. Genomics (1990) [Pubmed]
  25. Clinicopathologic and molecular-pathologic approaches to Lowe's syndrome. Hayashi, Y., Hanioka, K., Kanomata, N., Imai, Y., Itoh, H. Pediatric pathology & laboratory medicine : journal of the Society for Pediatric Pathology, affiliated with the International Paediatric Pathology Association. (1995) [Pubmed]
  26. Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes. Kawano, T., Indo, Y., Nakazato, H., Shimadzu, M., Matsuda, I. Am. J. Med. Genet. (1998) [Pubmed]
WikiGenes - Universities