Human Gene Module / Chromosome X / OCRL

OCRLoculocerebrorenal syndrome of Lowe

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 10
Rare Variants / Common Variants
7 / 0
Aliases
OCRL, INPP5F,  LOCR,  NPHL2-1,  OCRL1, OCRL
Associated Syndromes
Lowe syndrome
Chromosome Band
Xq26.1
Associated Disorders
-
Relevance to Autism

Mutations in the OCRL gene are responsible for Lowe syndrome (OMIM 309000), an X-linked multisystem disorder affecting the eyes, nervous system, and kidney. Maladaptive behaviors, including stereotypic/repetitive behavior, are frequently observed in Lowe syndrome cases (Kenworthy et al., 1993; Kenworth and Charnas, 1995). Evaluation of 52 patients with Lowe syndrome with the Autism Screening Questionnaire found that 71.2% of patients met the cut-off score for ASD and 34.6% met the cut-off score for autism (Oliver et al., 2011). A maternally-inherited duplication of Xq25 including full gene duplication of OCRL was identified in a male proband diagnosed with ASD and intellectual disability (Schroer et al., 2012).

Molecular Function

This gene encodes an inositol polyphosphate 5-phosphatase that is involved in regulating membrane trafficking and is located in numerous subcellular locations including the trans-Golgi network, clathrin-coated vesicles and, endosomes and the plasma membrane.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to OCRL (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Delineation of behavioral phenotypes in genetic syndromes: characteristics of autism spectrum disorder, affect and hyperactivity Oliver C , et al. (2010) No -
2 Support Duplication of OCRL and adjacent genes associated with autism but not Lowe syndrome Schroer RJ , et al. (2012) Yes -
3 Support Expanding the genetic heterogeneity of intellectual disability Anazi S , et al. (2017) No -
4 Support Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes Xiong J , et al. (2019) Yes Lowe syndrome
5 Support Diagnostic Yields of Trio-WES Accompanied by CNVseq for Rare Neurodevelopmental Disorders Gao C , et al. (2019) No -
6 Support - Chen S et al. (2021) Yes Epilepsy/seizures
7 Support - Álvarez-Mora MI et al. (2022) No -
8 Support - Karthika Ajit Valaparambil et al. () Yes -
9 Primary Cognitive and behavioral profile of the oculocerebrorenal syndrome of Lowe Kenworthy L , et al. (1993) No -
10 Support Evidence for a discrete behavioral phenotype in the oculocerebrorenal syndrome of Lowe Kenworthy L and Charnas L (1995) No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2428C>T p.Gln810Ter stop_gained De novo - - 31178897 Gao C , et al. (2019)
- - copy_number_gain Familial Maternal Simplex 22965764 Schroer RJ , et al. (2012)
c.2479C>T p.Gln827Ter stop_gained Unknown - Simplex 28940097 Anazi S , et al. (2017)
c.1880-2A>G - splice_site_variant Unknown - - 37943464 Karthika Ajit Valaparambil et al. ()
c.1926del p.Val643Ter frameshift_variant Familial Maternal - 34800434 Chen S et al. (2021)
c.1567G>A p.Asp523Asn missense_variant Familial Maternal - 35183220 Álvarez-Mora MI et al. (2022)
c.1925_1926del p.Ser642CysfsTer10 frameshift_variant Familial Maternal - 31031587 Xiong J , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Mutations in the OCRL gene are responsible for Lowe syndrome (OMIM 309000), an X-linked multisystem disorder affecting the eyes, nervous system, and kidney. Maladaptive behaviors, including stereotypic/repetitive behavior, are frequently observed in Lowe syndrome cases (Kenworthy et al., 1993; Kenworth and Charnas, 1995). Evaluation of 52 patients with Lowe syndrome with the Autism Screening Questionnaire found that 71.2% of patients met the cut-off score for ASD and 34.6% met the cut-off score for autism (Oliver et al., 2011). A maternally-inherited duplication of Xq25 including full gene duplication of OCRL was identified in a male proband diagnosed with ASD and intellectual disability (Schroer et al., 2012).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Mutations in the OCRL gene are responsible for Lowe syndrome (OMIM 309000), an X-linked multisystem disorder affecting the eyes, nervous system, and kidney. Maladaptive behaviors, including stereotypic/repetitive behavior, are frequently observed in Lowe syndrome cases (Kenworthy et al., 1993; Kenworth and Charnas, 1995). Evaluation of 52 patients with Lowe syndrome with the Autism Screening Questionnaire found that 71.2% of patients met the cut-off score for ASD and 34.6% met the cut-off score for autism (Oliver et al., 2011). A maternally-inherited duplication of Xq25 including full gene duplication of OCRL was identified in a male proband diagnosed with ASD and intellectual disability (Schroer et al., 2012).

Reports Added
[New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Mutations in the OCRL gene are responsible for Lowe syndrome (OMIM 309000), an X-linked multisystem disorder affecting the eyes, nervous system, and kidney. Maladaptive behaviors, including stereotypic/repetitive behavior, are frequently observed in Lowe syndrome cases (Kenworthy et al., 1993; Kenworth and Charnas, 1995). Evaluation of 52 patients with Lowe syndrome with the Autism Screening Questionnaire found that 71.2% of patients met the cut-off score for ASD and 34.6% met the cut-off score for autism (Oliver et al., 2011). A maternally-inherited duplication of Xq25 including full gene duplication of OCRL was identified in a male proband diagnosed with ASD and intellectual disability (Schroer et al., 2012).

Reports Added
[Diagnostic Yields of Trio-WES Accompanied by CNVseq for Rare Neurodevelopmental Disorders.2019]
4/1/2019
S
icon
S

Score remained at S

Description

Mutations in the OCRL gene are responsible for Lowe syndrome (OMIM 309000), an X-linked multisystem disorder affecting the eyes, nervous system, and kidney. Maladaptive behaviors, including stereotypic/repetitive behavior, are frequently observed in Lowe syndrome cases (Kenworthy et al., 1993; Kenworth and Charnas, 1995). Evaluation of 52 patients with Lowe syndrome with the Autism Screening Questionnaire found that 71.2% of patients met the cut-off score for ASD and 34.6% met the cut-off score for autism (Oliver et al., 2011). A maternally-inherited duplication of Xq25 including full gene duplication of OCRL was identified in a male proband diagnosed with ASD and intellectual disability (Schroer et al., 2012).

Reports Added
[Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.2019]
10/1/2017
S
icon
S

Score remained at S

Description

Mutations in the OCRL gene are responsible for Lowe syndrome (OMIM 309000), an X-linked multisystem disorder affecting the eyes, nervous system, and kidney. Maladaptive behaviors, including stereotypic/repetitive behavior, are frequently observed in Lowe syndrome cases (Kenworthy et al., 1993; Kenworth and Charnas, 1995). Evaluation of 52 patients with Lowe syndrome with the Autism Screening Questionnaire found that 71.2% of patients met the cut-off score for ASD and 34.6% met the cut-off score for autism (Oliver et al., 2011). A maternally-inherited duplication of Xq25 including full gene duplication of OCRL was identified in a male proband diagnosed with ASD and intellectual disability (Schroer et al., 2012).

Reports Added
[Expanding the genetic heterogeneity of intellectual disability.2017]
Krishnan Probability Score

Score 0.495401408548

Ranking 2995/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99991829802926

Ranking 652/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.93851965293377

Ranking 13891/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.41837562371508

Ranking 1257/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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