Human Gene Module / Chromosome X / BCORL1

BCORL1BCL6 corepressor like 1

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 8
Rare Variants / Common Variants
14 / 0
Aliases
BCORL1, BCoR-L1,  CXorf10
Associated Syndromes
-
Chromosome Band
Xq26.1
Associated Disorders
ADHD, ASD, EPS
Relevance to Autism

Shukla et al., 2019 reported five individuals from three pedigrees with maternally-inherited missense variants in the BCORL1 gene that presented with an X-linked neurodevelopmental disorder characterized by intellectual disability, behavioral abnormalities, and dysmorphic features; autism spectrum disorder was reported in all five individuals in this report. A rare de novo missense variant in this gene had previously been identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Molecular Function

The protein encoded by this gene is a transcriptional corepressor that is found tethered to promoter regions by DNA-binding proteins. The encoded protein can interact with several different class II histone deacetylases to repress transcription.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to BCORL1 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary Variants in the transcriptional corepressor BCORL1 are associated with an X-linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities Shukla A , et al. (2019) Yes ADHD, epilepsy/seizures, dysmorphic features
3 Support Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population Monies D , et al. (2019) No Autistic features
4 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
5 Support - Bertoli-Avella AM et al. (2021) No -
6 Support - Gafner M et al. (2021) No Autistic features
7 Support - Brea-Fernández AJ et al. (2022) No -
8 Support - Zhou X et al. (2022) Yes -
Rare Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1624G>A p.Asp542Asn missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4606C>T p.Arg1536Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4491G>A p.Glu1497%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1584C>G p.Cys528Trp missense_variant Unknown - Unknown 31130284 Monies D , et al. (2019)
c.2390G>A p.Cys797Tyr missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2345T>A p.Val782Glu missense_variant Familial Maternal - 30941876 Shukla A , et al. (2019)
c.4594_4608del p.Thr1532_Glu1536del inframe_deletion De novo - - 35982159 Zhou X et al. (2022)
c.1832T>C p.Met611Thr missense_variant De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.3230_3231delinsTT p.Arg1077Ile missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.95C>T p.Pro32Leu missense_variant Familial Maternal Multiplex 30941876 Shukla A , et al. (2019)
c.3376G>A p.Asp1126Asn missense_variant Familial Maternal Simplex 34400773 Gafner M et al. (2021)
c.796C>T p.Pro266Ser missense_variant Familial Maternal Multiplex 34400773 Gafner M et al. (2021)
c.1487C>T p.Ser496Phe missense_variant Familial Maternal Simplex 30941876 Shukla A , et al. (2019)
c.1562_1563del p.Leu521ArgfsTer13 frameshift_variant De novo - Simplex 33875846 Bertoli-Avella AM et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Shukla et al., 2019 reported five individuals from three pedigrees with maternally-inherited missense variants in the BCORL1 gene that presented with an X-linked neurodevelopmental disorder characterized by intellectual disability, behavioral abnormalities, and dysmorphic features; autism spectrum disorder was reported in all five individuals in this report. A rare de novo missense variant in this gene had previously been identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

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."

4/1/2021
S
icon
S

Score remained at S

Description

Shukla et al., 2019 reported five individuals from three pedigrees with maternally-inherited missense variants in the BCORL1 gene that presented with an X-linked neurodevelopmental disorder characterized by intellectual disability, behavioral abnormalities, and dysmorphic features; autism spectrum disorder was reported in all five individuals in this report. A rare de novo missense variant in this gene had previously been identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Reports Added
[Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders2021]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Shukla et al., 2019 reported five individuals from three pedigrees with maternally-inherited missense variants in the BCORL1 gene that presented with an X-linked neurodevelopmental disorder characterized by intellectual disability, behavioral abnormalities, and dysmorphic features; autism spectrum disorder was reported in all five individuals in this report. A rare de novo missense variant in this gene had previously been identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
Krishnan Probability Score

Score 0.4973277540572

Ranking 2407/25841 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 0.98179031164007

Ranking 2080/18225 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 0.90110934183379

Ranking 6492/18665 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 0.14145487608906

Ranking 5328/20870 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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