Human Gene Module / Chromosome X / PCDH11X

PCDH11Xprotocadherin 11 X-linked

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
5 / 0
EAGLE Score
1.1
Limited Learn More
Aliases
PCDH11X, PCDH-X,  PCDH11,  PCDHX,  PPP1R119
Associated Syndromes
-
Chromosome Band
Xq21.31
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

A LoF variant in the PCDH11X gene was identified in a male ASD proband, but not in male or female controls, in Lim et al., 2013. A second LoF variant in this gene was identifed in a male ASD proband by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple LoF variants and a probability of LoF intolerance rate (pLI) > 0.65, PCDH11X was determined to be an ASD candidate gene in Yuen et al., 2017.

Molecular Function

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PCDH11X (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders Lim ET , et al. (2013) Yes -
2 Recent Recommendation Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Miyake N et al. (2023) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3033+3633G>A - splice_site_variant Unknown - Unknown 23352160 Lim ET , et al. (2013)
c.3052C>T p.Arg1018Ter stop_gained Unknown - Simplex 28263302 C Yuen RK et al. (2017)
c.2127A>C p.Ala709%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1684G>C p.Asp562His missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.37C>A p.Leu13Met missense_variant Familial Maternal Simplex 36973392 Miyake N et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A LoF variant in the PCDH11X gene was identified in a male ASD proband, but not in male or female controls, in Lim et al., 2013. A second LoF variant in this gene was identifed in a male ASD proband by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple LoF variants and a probability of LoF intolerance rate (pLI) > 0.65, PCDH11X was determined to be an ASD candidate gene in Yuen et al., 2017.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A LoF variant in the PCDH11X gene was identified in a male ASD proband, but not in male or female controls, in Lim et al., 2013. A second LoF variant in this gene was identifed in a male ASD proband by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple LoF variants and a probability of LoF intolerance rate (pLI) > 0.65, PCDH11X was determined to be an ASD candidate gene in Yuen et al., 2017.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A LoF variant in the PCDH11X gene was identified in a male ASD proband, but not in male or female controls, in Lim et al., 2013. A second LoF variant in this gene was identifed in a male ASD proband by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple LoF variants and a probability of LoF intolerance rate (pLI) > 0.65, PCDH11X was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[New Scoring Scheme]
4/1/2017
icon
4

Increased from to 4

Description

A LoF variant in the PCDH11X gene was identified in a male ASD proband, but not in male or female controls, in Lim et al., 2013. A second LoF variant in this gene was identifed in a male ASD proband by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of multiple LoF variants and a probability of LoF intolerance rate (pLI) > 0.65, PCDH11X was determined to be an ASD candidate gene in Yuen et al., 2017.

Krishnan Probability Score

Score 0.5789906380741

Ranking 598/25841 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 0.9257421249015

Ranking 2970/18225 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 0.94874316604492

Ranking 17808/18665 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
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