Human Gene Module / Chromosome 13 / PCDH9

PCDH9protocadherin 9

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 7
Rare Variants / Common Variants
7 / 1
Aliases
PCDH9, RP11-335P18.3
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
13q21.32
Associated Disorders
ID
Relevance to Autism

Rare mutations in the PCDH9 gene have been identified with autism (Marshall et al., 2008). As well, a rare deletion of the PCDH9 gene was found in a patient with PDD-NOS and mild intellectual disability (Leblond et al., 2012).

Molecular Function

encodes a cadherin-related neuronal receptor that localizes to synaptic junction s

Reports related to PCDH9 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation Spatiotemporal expression pattern of non-clustered protocadherin family members in the developing rat brain. Kim SY , et al. (2007) No -
2 Primary Structural variation of chromosomes in autism spectrum disorder. Marshall CR , et al. (2008) Yes -
3 Support Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. Leblond CS , et al. (2012) Yes ID
4 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder. Prasad A , et al. (2013) Yes -
5 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Girirajan S , et al. (2013) Yes -
6 Positive Association The Gene Encoding Protocadherin 9 (PCDH9), a Novel Risk Factor for Major Depressive Disorder. Xiao X , et al. (2017) No -
7 Highly Cited Characterization of two novel protocadherins (PCDH8 and PCDH9) localized on human chromosome 13 and mouse chromosome 14. Strehl S , et al. (1998) No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_gain Unknown - Simplex 18252227 Marshall CR , et al. (2008)
- - copy_number_gain Unknown - Unknown 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Paternal Simplex 22346768 Leblond CS , et al. (2012)
- - copy_number_gain Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Multiplex 18252227 Marshall CR , et al. (2008)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.3215-43545T>C;c.3113-43545T>C;c.3239-43545T>C;c.3341-43545T>C - intron_variant - - - 28990594 Xiao X , et al. (2017)
SFARI Gene score
3

Suggestive Evidence

A single, unreplicated association of CNVs has been reported by Marshall et al., 2008 (PMID: 18252227).

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, unreplicated association of CNVs has been reported by Marshall et al., 2008 (PMID: 18252227).

Reports Added
[New Scoring Scheme]
10/1/2017
4
icon
4

Decreased from 4 to 4

Description

A single, unreplicated association of CNVs has been reported by Marshall et al., 2008 (PMID: 18252227).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

A single, unreplicated association of CNVs has been reported by Marshall et al., 2008 (PMID: 18252227).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A single, unreplicated association of CNVs has been reported by Marshall et al., 2008 (PMID: 18252227).

Krishnan Probability Score

Score 0.6258472874055

Ranking 73/25841 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 0.97301427734079

Ranking 2302/18225 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 0.94924216889301

Ranking 18011/18665 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 0.10256779024961

Ranking 6079/20870 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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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