OCRL
OCRL inositol polyphosphate-5-phosphatase, the group of Phosphoinositide phosphatases
Basic information
Region (hg38): X:129539848-129592561
Links
Phenotypes
GenCC
Source:
- oculocerebrorenal syndrome (Definitive), mode of inheritance: XLR
- Dent disease type 2 (Definitive), mode of inheritance: XLR
- oculocerebrorenal syndrome (Strong), mode of inheritance: XL
- oculocerebrorenal syndrome (Definitive), mode of inheritance: XL
- Dent disease type 2 (Definitive), mode of inheritance: XL
- oculocerebrorenal syndrome (Supportive), mode of inheritance: XL
- Dent disease type 2 (Supportive), mode of inheritance: XL
- Dent disease type 2 (Strong), mode of inheritance: XL
- oculocerebrorenal syndrome (Definitive), mode of inheritance: XL
- oculocerebrorenal syndrome (Definitive), mode of inheritance: XL
- Dent disease type 2 (Definitive), mode of inheritance: XL
- Dent disease type 2 (Strong), mode of inheritance: XL
- oculocerebrorenal syndrome (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Dent disease 2; Lowe syndrome | XL | Pharmacogenomic; Renal | In Dent disease, surveillance and treatment related to manifestations such as hypercalciuria in order to prevent kidney stones, nephrocalcinosis, and to delay the progression of kidney dysfunction may be beneficial (though efficacy is unclear, treatment may include thiazide diuretics, ACE inhibitors, and ARBs); Vitamin D and phosphorous may be beneficial related to skeletal manifestations; Growth hormone may be indicated; Nephrotoxic agents (eg, NSAIDs, aminoglycosides) should be avoided; In Lowe syndrome, which may represent the severe end of of the spectrum of variant-positive individuals, similar treatment related to renal manifestations may be beneficial, as well as care related to other organ systems | Musculoskeletal; Neurologic; Ophthalmologic; Renal | 8504307; 9199559; 9632163; 9682219; 199559; 9917791; 10364518; 0923037; 10767176; 15627218; 17162149; 19390221; 21031565 |
ClinVar
This is a list of variants' phenotypes submitted to
- Lowe syndrome (373 variants)
- not provided (127 variants)
- not specified (24 variants)
- Dent disease type 2;Lowe syndrome (19 variants)
- Dent disease type 2 (17 variants)
- Inborn genetic diseases (14 variants)
- Nephrolithiasis/nephrocalcinosis;Inborn genetic diseases (12 variants)
- Inborn genetic diseases;Nephrolithiasis/nephrocalcinosis (11 variants)
- Lowe syndrome;Dent disease type 2 (7 variants)
- OCRL-related condition (6 variants)
- Dent disease (2 variants)
- Developmental cataract (1 variants)
- Neurodevelopmental delay (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the OCRL gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 65 | 77 | ||||
| missense | 14 | 103 | 27 | 154 | ||
| nonsense | 17 | 21 | ||||
| start loss | 0 | |||||
| frameshift | 24 | 32 | ||||
| inframe indel | 4 | |||||
| splice donor/acceptor (+/-2bp) | 13 | 21 | ||||
| splice region ? | 16 | 22 | 3 | 41 | ||
| non coding ? | 63 | 32 | 98 | |||
| Total | 58 | 39 | 111 | 155 | 44 |
Variants in OCRL
This is a list of pathogenic ClinVar variants found in the OCRL region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| X-129539976-AAT-A | Benign (Nov 06, 2019) | |||
| X-129539976-A-AAT | Benign (Jan 06, 2020) | |||
| X-129539976-A-AATAT | Benign (Apr 04, 2020) | |||
| X-129539976-A-AATATATAT | Likely benign (Dec 19, 2020) | |||
| X-129539986-TA-T | Likely benign (May 05, 2020) | |||
| X-129540157-C-T | Benign (Jul 27, 2018) | |||
| X-129540176-C-T | Benign (Jul 27, 2018) | |||
| X-129540450-C-T | Dent disease type 2;Lowe syndrome • Lowe syndrome • Nephrolithiasis/nephrocalcinosis | Likely benign (Jan 14, 2024) | ||
| X-129540451-G-C | Lowe syndrome | Likely benign (May 08, 2023) | ||
| X-129540454-C-G | Lowe syndrome | Likely benign (Sep 27, 2022) | ||
| X-129540456-C-G | Lowe syndrome | Likely benign (Jan 30, 2024) | ||
| X-129540456-C-T | Lowe syndrome | Likely benign (Jul 16, 2023) | ||
| X-129540457-G-A | Likely benign (Jan 01, 2023) | |||
| X-129540458-G-T | Intellectual disability | Uncertain significance (Jan 16, 2020) | ||
| X-129540460-C-T | Lowe syndrome | Likely benign (Dec 14, 2023) | ||
| X-129540464-G-A | Uncertain significance (Feb 17, 2017) | |||
| X-129540466-C-T | Lowe syndrome | Likely benign (May 13, 2023) | ||
| X-129540468-A-T | Lowe syndrome | Uncertain significance (Dec 22, 2023) | ||
| X-129540472-G-A | Lowe syndrome | Likely benign (Jan 04, 2024) | ||
| X-129540486-C-T | Lowe syndrome • OCRL-related disorder | Likely benign (Dec 20, 2023) | ||
| X-129540487-C-G | Lowe syndrome | Likely benign (Jan 28, 2024) | ||
| X-129540488-G-A | Lowe syndrome • not specified • OCRL-related disorder | Conflicting classifications of pathogenicity (Jan 29, 2024) | ||
| X-129540492-A-C | Lowe syndrome | Likely benign (Feb 10, 2023) | ||
| X-129540492-AGAAG-A | Lowe syndrome | Likely benign (Apr 10, 2023) | ||
| X-129540493-G-A | Lowe syndrome | Likely benign (Apr 25, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| OCRL | protein_coding | protein_coding | ENST00000371113 | 24 | 52713 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000119 | 125734 | 1 | 1 | 125736 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.96 | 194 | 350 | 0.554 | 0.0000274 | 6016 |
| Missense in Polyphen | 45 | 140.19 | 0.32099 | 2487 | ||
| Synonymous | 0.490 | 111 | 118 | 0.943 | 0.00000859 | 1633 |
| Loss of Function | 5.62 | 2 | 40.7 | 0.0492 | 0.00000331 | 619 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000760 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000122 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. Also converts inositol 1,4,5- trisphosphate to inositol 1,4-bisphosphate and inositol 1,3,4,5- tetrakisphosphate to inositol 1,3,4-trisphosphate (PubMed:25869668, PubMed:7761412, PubMed:9430698). May function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes. Involved in primary cilia assembly (PubMed:22228094, PubMed:22543976). {ECO:0000269|PubMed:22228094, ECO:0000269|PubMed:22543976, ECO:0000269|PubMed:25869668, ECO:0000269|PubMed:7761412, ECO:0000269|PubMed:9430698}.;
- Disease
- DISEASE: Lowe oculocerebrorenal syndrome (OCRL) [MIM:309000]: X- linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. Ocular abnormalities include cataract, glaucoma, microphthalmos, and decreased visual acuity. Developmental delay, hypotonia, behavior abnormalities, and areflexia are also present. Renal tubular involvement is characterized by impaired reabsorption of bicarbonate, amino acids, and phosphate. Musculoskeletal abnormalities such as joint hypermobility, dislocated hips, and fractures may develop as consequences of renal tubular acidosis and hypophosphatemia. Cataract is the only significant manifestation in carriers and is detected by slit-lamp examination. {ECO:0000269|PubMed:10767176, ECO:0000269|PubMed:10923037, ECO:0000269|PubMed:19168822, ECO:0000269|PubMed:20133602, ECO:0000269|PubMed:21031565, ECO:0000269|PubMed:21233288, ECO:0000269|PubMed:9199559, ECO:0000269|PubMed:9632163, ECO:0000269|PubMed:9682219, ECO:0000269|PubMed:9788721}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dent disease 2 (DD2) [MIM:300555]: A renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Characteristic abnormalities include low-molecular-weight proteinuria and other features of Fanconi syndrome, such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones. {ECO:0000269|PubMed:15627218, ECO:0000269|PubMed:17384968, ECO:0000269|PubMed:21031565}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Signal Transduction;D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis;superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism;Vesicle-mediated transport;Membrane Trafficking;Metabolism of lipids;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis II (mammalian);Inositol phosphate metabolism;3-phosphoinositide degradation;D-<i>myo</i>-inositol (1,4,5)-trisphosphate degradation;Metabolism;superpathway of inositol phosphate compounds;Rho GTPase cycle;Phosphatidylinositol phosphate metabolism;Signaling by Rho GTPases;Clathrin-mediated endocytosis;Synthesis of IP3 and IP4 in the cytosol;Inositol phosphate metabolism;Synthesis of PIPs at the Golgi membrane;Synthesis of PIPs at the plasma membrane;PI Metabolism;Phospholipid metabolism;Synthesis of IP2, IP, and Ins in the cytosol
(Consensus)
Recessive Scores
- pRec
- 0.0972
Intolerance Scores
- loftool
- 0.00744
- rvis_EVS
- -0.25
- rvis_percentile_EVS
- 35.99
Haploinsufficiency Scores
- pHI
- 0.334
- hipred
- Y
- hipred_score
- 0.853
- ghis
- 0.572
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.546
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ocrl
- Phenotype
- homeostasis/metabolism phenotype; growth/size/body region phenotype; renal/urinary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype;
Zebrafish Information Network
- Gene name
- ocrl
- Affected structure
- melanocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- lipid metabolic process;phosphatidylinositol biosynthetic process;signal transduction;phosphatidylinositol-3-phosphate biosynthetic process;regulation of GTPase activity;positive regulation of GTPase activity;inositol phosphate metabolic process;inositol phosphate dephosphorylation;phosphatidylinositol dephosphorylation;regulation of small GTPase mediated signal transduction;cilium assembly;membrane organization
- Cellular component
- photoreceptor outer segment;nucleus;cytoplasm;early endosome;Golgi stack;Golgi-associated vesicle;trans-Golgi network;cytosol;plasma membrane;clathrin-coated pit;membrane;clathrin-coated vesicle;phagocytic vesicle membrane;early endosome membrane
- Molecular function
- phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity;GTPase activator activity;protein binding;phosphatidylinositol phosphate 4-phosphatase activity;phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity;Rac GTPase binding;inositol-1,4,5-trisphosphate 5-phosphatase activity;inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity;inositol phosphate phosphatase activity