Inositol polyphosphate 5-phosphatase OCRL: Difference between revisions

==  Oculocerebrorenal syndrome of Lowe ==

Lowe syndrome, formally called oculocerebrorenal syndrome, oculocerebrorenal syndrome of Lowe or OCRL, is an X-linked multisystemic disorder mainly involving eyes, nervous system (both the central and the peripheral) and kidneys caused by mutations in OCRL1 protein. The syndrome is quite rare, its prevalence is 1 in 500 000 in the general population (based on the observations of the American Lowe Syndrome Association and the Italian Association of Lowe syndrome). Almost all of the patients are male. The syndrome is believed to occur worldwide as there are documented cases in America, Europe, Australia, Japan and India.<ref name="Lowe syndrome">PMID: 20301653</ref><ref name="Oculocerebrorenal">PMID: 27011217</ref>

OCRL1 has been also reported to localize to the basal body and the transition zone of the primary cilium. Therefore, it also participates in ciliogenesis by contributing to protein trafficking to this organelle in an Rab8/IPIP27-dependent manner.<ref name="cilia">PMID: 22228094</ref>

== Mutations in OCRL1 ==

The N591K mutation also causes significant reduction in binding of Rab8a proteins but the reason for this is different than in the case of F668V mutation. This AA is not part of any binding site but it seems to be important in the maintenance of the correct features of the ASH domain which are essential for Rab8a binding. The effect of this mutation was studied in silico and it showed that the mutation causes the ASH domain to alter its flexibility and overall fold. Although the highest change was observed in the AAs that surrounds the N591K mutation, the substitution caused subsequent changes in most parts of the protein which had brought about decreases of prevalence of hydrogen bonds between Rab8a and OCRL1 which led to a lower stability of their interaction.<ref name="com"/>

== References ==

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