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OCRL

OCRL inositol polyphosphate-5-phosphatase

The OCRL gene provides instructions for an enzyme critical in cell membrane phospholipid modification, endocytosis, and kidney function, with pathogenic variants linked to conditions like Lowe syndrome and Dent disease 2. The OCRL gene encodes an enzyme called OCRL inositol polyphosphate-5-phosphatase.

Chromosome Xq26.1 X-linked HGNC:8108 Tier C
OCRL Xq26.1 p arm q arm X

OCRL is located on the long (q) arm of chromosome X, at band Xq26.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome X in the library →

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Clinical tests that include this

Carrier Screening panel
OCRL is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The OCRL gene, formally known as OCRL inositol polyphosphate-5-phosphatase, is responsible for producing an enzyme that modifies specific fat molecules called membrane phospholipids. These phospholipids are fundamental components of cell membranes. This enzyme is crucial for various cellular processes, including the sorting and transport of molecules within cells, a process known as endocytosis.

Dysfunction of the OCRL enzyme, often due to pathogenic variants in the gene, is associated with inherited conditions that primarily affect the kidneys, eyes, and brain.

What the gene does

The OCRL enzyme plays a key role in cellular membrane dynamics by modifying membrane phospholipids. It is particularly concentrated in the trans-Golgi network, which is involved in directing proteins and other molecules to their correct locations within the cell. Additionally, OCRL is found in endosomes, which are compartments that facilitate the movement of proteins and other substances into the cell from its exterior. These processes are collectively known as endocytosis.

Endocytosis is especially important in the kidney's proximal tubular cells, where OCRL contributes to the reabsorption of proteins and essential nutrients back into the bloodstream. Recent research also indicates that OCRL is involved in the formation of cilia, which are microscopic, finger-like projections on cell surfaces crucial for the structure and function of various cell types, including those in the eyes and kidneys.

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Chromosome location

The OCRL gene is located on the long arm of the X chromosome at position Xq26.1. As an X-linked gene, conditions associated with OCRL typically manifest differently in males and females.

Protein structure

The OCRL protein is 901 amino acids long and features several distinct functional regions. It contains an N-terminal PH domain (amino acids 1-119) and a 5-PPase domain (amino acids 235-538). Additionally, there are a Disordered region (amino acids 164-186), an ASH region (amino acids 564-678), and a Rho-GAP domain (amino acids 721-901). Two Clathrin box motifs are also present, one at amino acids 73-77 and another at amino acids 702-706.

Domain map · 901 amino acids
PH (1–119)Clathrin box 1 (73–77)5-PPase (235–538)ASH (564–678)Clathrin box 2 (702–706)Rho-GAP (721–901)PH1–1195-PPase235–538Rho-GAP721–9011~451901
Domain - independent functional unit
Motif - short conserved sequence
Region - functional region
🧬 Explore 3D structure on AlphaFold
UniProt:Q01968Length:901 aaStructure:AlphaFold

Key variants

Genetic changes, or variants, within the OCRL gene can alter the function of the OCRL enzyme. Some pathogenic variants may lead to a non-functional enzyme, while others might prevent its production entirely. These changes can disrupt critical cellular processes, particularly affecting kidney function and other systems.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for OCRL.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1244+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Lowe syndrome
c.1442_1443del
Microsatellite
 p.Asp480_Ser481insTer Pathogenic ★★☆☆ Lowe syndrome
c.1498C>T
single nucleotide variant
 p.Arg500Ter Pathogenic ★★☆☆ Lowe syndrome
c.1567G>A
single nucleotide variant
 p.Asp523Asn Pathogenic ★★☆☆ not provided
c.1753_1755del
Deletion
 p.Glu585del Pathogenic/Likely pathogenic ★★☆☆ OCRL-related disorder
c.1925_1926del
Microsatellite
 p.Ser642fs Pathogenic ★★☆☆ Lowe syndrome
c.1987C>T
single nucleotide variant
 p.Arg663Ter Pathogenic ★★☆☆ OCRL-related disorder
c.2083C>T
single nucleotide variant
 p.Arg695Ter Pathogenic/Likely pathogenic ★★☆☆ OCRL-related disorder
c.2309_2312del
Microsatellite
 p.Asp770fs Pathogenic ★★☆☆ Lowe syndrome
c.2581G>A
single nucleotide variant
 p.Ala861Thr Pathogenic/Likely pathogenic ★★☆☆ Lowe syndrome

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the OCRL gene are primarily associated with two distinct inherited conditions: Lowe syndrome and a type of Dent disease known as Dent disease 2. Both conditions are X-linked and predominantly affect males. Lowe syndrome affects the eyes, brain, and kidneys, while Dent disease 2 primarily causes chronic kidney disease, which can progress to kidney failure, and may also involve developmental delays and mild intellectual disabilities.

Inheritance pattern

Conditions caused by pathogenic OCRL variants typically follow x-linked inheritance.

♀ Carrier mother 1 altered X ♂ Unaffected father Typical Y Carrier daughter Unaffected daughter Affected son Unaffected son Affected Carrier Unaffected Circles = females · Squares = males

X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.

Carrier frequency by population How common is heterozygous OCRL carrier status across ancestry groups?

UK clinical status

The OCRL gene is included in several NHS England Genomic Medicine Service panels, indicating its recognised clinical importance within the UK. These panels cover a range of conditions, including Bilateral congenital or childhood onset cataracts (R31), Foetal anomalies (R21), Glaucoma (developmental), Hypophosphataemia or rickets (R154), Intellectual disability, Likely inborn error of metabolism (R98), Nephrocalcinosis or nephrolithiasis (R256), Proteinuric renal disease (R195), Renal tubulopathies (R198), Structural eye disease (R36), and Undiagnosed metabolic disorders. It is also part of the DDG2P (Developmental Disorders Genotype-Phenotype Database) gene list.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Bilateral congenital or childhood onset cataracts · R31 NHS GMS → Fetal anomalies · R21 NHS GMS → Hypophosphataemia or rickets · R154 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Nephrocalcinosis or nephrolithiasis · R256 NHS GMS → Proteinuric renal disease · R195 NHS GMS → Renal tubulopathies · R198 NHS GMS → Structural eye disease · R36 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the OCRL gene?

The OCRL gene provides instructions for an enzyme that modifies specific fat molecules (phospholipids) in cell membranes. This enzyme is crucial for cellular processes like endocytosis, especially in kidney cells for reabsorbing proteins and nutrients.

What conditions are associated with pathogenic variants in the OCRL gene?

Pathogenic variants in the OCRL gene are primarily associated with Lowe syndrome and Dent disease 2. Both are X-linked conditions that mainly affect males, impacting organs such as the kidneys, eyes, and brain.

Why is OCRL considered an X-linked gene?

OCRL is located on the X chromosome, meaning conditions caused by pathogenic variants in this gene follow an X-linked inheritance pattern. This typically results in different disease presentations between males, who have one X chromosome, and females, who have two.

References

  1. Coon BG, Hernandez V, Madhivanan K. The Lowe syndrome protein OCRL1 is involved in primary cilia assembly. Human molecular genetics. 2012. PMID: 22228094
  2. Pirruccello M, De Camilli P. Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL. Trends in biochemical sciences. 2012. PMID: 22381590
  3. Luo N, West CC, Murga-Zamalloa CA. OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Human molecular genetics. 2012. PMID: 22543976
  4. Claverie-Martín F, Ramos-Trujillo E, García-Nieto V. Dent's disease: clinical features and molecular basis. Pediatric nephrology (Berlin, Germany). 2011. PMID: 20936522
  5. Hichri H, Rendu J, Monnier N. From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. Human mutation. 2011. PMID: 21031565
  6. McCrea HJ, Paradise S, Tomasini L. All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding. Biochemical and biophysical research communications. 2008. PMID: 18307981
  7. Erdmann KS, Mao Y, McCrea HJ. A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway. Developmental cell. 2007. PMID: 17765681
  8. Hyvola N, Diao A, McKenzie E. Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. The EMBO journal. 2006. PMID: 16902405
  9. Utsch B, Bökenkamp A, Benz MR. Novel OCRL1 mutations in patients with the phenotype of Dent disease. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2006. PMID: 17162149
  10. Hoopes RR Jr, Shrimpton AE, Knohl SJ. Dent Disease with mutations in OCRL1. American journal of human genetics. 2005. PMID: 15627218
  11. Choudhury R, Diao A, Zhang F. Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network. Molecular biology of the cell. 2005. PMID: 15917292
  12. Lowe M. Structure and function of the Lowe syndrome protein OCRL1. Traffic (Copenhagen, Denmark). 2005. PMID: 16101675
  13. Adam MP, Bick S, Mirzaa GM. Lowe Syndrome. 1993. PMID: 20301653
  14. Attree O, Olivos IM, Okabe I. The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Nature. 1992. PMID: 1321346
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .