Renal tubulopathies

Gene: OCRL

Comment on list classification: Upgrading from Red to Amber but this gene should be promoted to Green at the next GMS panel update, in line with the review by Beccy Cummings (NHS).

Variants in the OCRL gene cause Dent disease, a disorder of proximal renal tubular dysfunction, which could plausibly be picked up via this panel and therefore warrants inclusion.

Created: 16 Jun 2025, 9:39 a.m. | Last Modified: 16 Jun 2025, 9:39 a.m.

Panel Version: 5.3

Green List (high evidence)

Please can this gene be green in the tubulopathy panel. While we appreciate these genes are on the Nephrocalcinosis panel (R265) and the Proteinuric renal disease panel (R195), more often than not children with Dent don’t have nephrocalcinosis or proteinuria so they wouldn’t meet the criteria for either of those panels.

Created: 4 Jun 2025, 8:04 a.m. | Last Modified: 4 Jun 2025, 8:04 a.m.

Panel Version: 5.1

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 2:43 p.m. | Last Modified: 10 Dec 2025, 2:43 p.m.

Panel Version: 5.10

Comment on list classification: After consultation with the Genomics England rare disease clinical team leaving this gene red on this panel as Dent disease is covered by the 'R256 Nephrocalcinosis or nephrolithiasis' panel.

Created: 5 Sep 2019, 8:25 p.m. | Last Modified: 5 Sep 2019, 8:25 p.m.

Panel Version: 1.140

Associated with Dent disease 2 #300555 and Lowe syndrome #309000 in OMIM both with reported renal clinical features.

Many cases of association between variants in OCRL and these diseases reported in OMIM.
e.g. PMID: 10364518 (Satre et al 1999) reports on 8 famlies with Lowe Syndrome. Five of these eight pedigrees had a family history of at least two male patients carrying a clinical diagnosis of Lowe syndrome on the basis of the classic triad of defects affecting lens, brain and kidney. Seven new mutations and one recurrent mutation were identified in the OCRL1 gene in one carrier mother and in seven affected patients. They identified a germ-line mosaicism in one family.

Created: 31 Aug 2019, 5:48 p.m. | Last Modified: 31 Aug 2019, 5:48 p.m.

Panel Version: 1.82

This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: OCRL; Suggested initial gene rating: green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided

Created: 3 Feb 2019, 11:32 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Dent disease 2, MIM 300555. Lowe syndrome, MIM 309000

Variants in this GENE are reported as part of current diagnostic practice