Human Gene Module / Chromosome 4 / PCDH10

PCDH10protocadherin 10

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 8
Rare Variants / Common Variants
4 / 0
Aliases
PCDH10, PCDH19,  OL-PCDH,  KIAA1400,  MGC133344,  DKFZP761O2023
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
4q28.3
Associated Disorders
-
Relevance to Autism

Rare variants in the PCDH10 gene have been identified with autism in the HMCA cohort (Morrow et al., 2008).

Molecular Function

encodes a cadherin-related neuronal receptor thought to play a role in the estab lishment and function of specific cell-cell connections in the brain.

Reports related to PCDH10 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation OL-Protocadherin is essential for growth of striatal axons and thalamocortical projections. Uemura M , et al. (2007) No -
2 Primary Identifying autism loci and genes by tracing recent shared ancestry. Morrow EM , et al. (2008) Yes -
3 Recent Recommendation Contact-dependent promotion of cell migration by the OL-protocadherin-Nap1 interaction. Nakao S , et al. (2008) No -
4 Support Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95. Tsai NP , et al. (2012) No -
5 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No -
6 Support Genome-wide characteristics of de novo mutations in autism. Yuen RK , et al. (2016) Yes -
7 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder. Takata A , et al. (2018) Yes -
8 Highly Cited Expression of a novel protocadherin, OL-protocadherin, in a subset of functional systems of the developing mouse brain. Hirano S , et al. (1999) No -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.*1124T>G - 3_prime_UTR_variant De novo NA Simplex 27525107 Yuen RK , et al. (2016)
- - copy_number_loss Familial Both parents Simplex 18621663 Morrow EM , et al. (2008)
c.2466G>C p.Gln822His missense_variant De novo NA Simplex 29346770 Takata A , et al. (2018)
c.1813G>A p.Ala605Thr missense_variant De novo NA Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

A single rare CNV in the PCDH10 gene was observed with autism (PMID: 18621663).

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A single rare CNV in the PCDH10 gene was observed with autism (PMID: 18621663).

Reports Added
[New Scoring Scheme]
7/1/2016
4
icon
4

Decreased from 4 to 4

Description

A single rare CNV in the PCDH10 gene was observed with autism (PMID: 18621663).

1/1/2015
4
icon
4

Decreased from 4 to 4

Description

A single rare CNV in the PCDH10 gene was observed with autism (PMID: 18621663).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

A single rare CNV in the PCDH10 gene was observed with autism (PMID: 18621663).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A single rare CNV in the PCDH10 gene was observed with autism (PMID: 18621663).

Krishnan Probability Score

Score 0.56748818343886

Ranking 1177/25841 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.
ExAC Score

Score 0.89443021344704

Ranking 3270/18225 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
Sanders TADA Score

Score 0.94673222783228

Ranking 16989/18665 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).
Zhang D Score

Score -0.019254785906904

Ranking 9325/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
BEX1 brain expressed, X-linked 1 Human Protein Binding 55859 Q9HBH7
FCGRT IgG receptor FcRn large subunit p51 Human Protein Binding 2217 P55899
PCDH12 Protocadherin-12 Human Protein Binding 51294 Q9NPG4
SLC34A2 Sodium-dependent phosphate transport protein 2B Human Protein Binding 10568 O95436-2
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