Human Gene Module / Chromosome 16 / CDH13

CDH13cadherin 13

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
6 / 0
Aliases
CDH13, CDHH,  P105
Associated Syndromes
-
Chromosome Band
16q23.3
Associated Disorders
-
Relevance to Autism

A de novo missense variant that was predicted to be damaging was observed in the CDH13 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the CDH13 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [4 CNVs from ASD cases and 4 CNVs from SCZ cases (8 total) vs. 0 CNVs in controls (Odds ratio 10.02, P = 8.6E-03)].

Molecular Function

This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CDH13 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights Kushima I , et al. (2018) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Recent Recommendation - Mossink B et al. (2021) No -
5 Support - Woodbury-Smith M et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - - 30208311 Kushima I , et al. (2018)
c.1822+2T>G - splice_site_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.786G>A p.Val262= synonymous_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1565C>T p.Pro522Leu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1307A>G p.Asp436Gly missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.600dup p.Pro201AlafsTer12 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo missense variant that was predicted to be damaging was observed in the CDH13 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the CDH13 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [4 CNVs from ASD cases and 4 CNVs from SCZ cases (8 total) vs. 0 CNVs in controls (Odds ratio 10.02, P = 8.6E-03)].

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.

4/1/2021
2
icon
2

Score remained at 2

Description

A de novo missense variant that was predicted to be damaging was observed in the CDH13 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the CDH13 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [4 CNVs from ASD cases and 4 CNVs from SCZ cases (8 total) vs. 0 CNVs in controls (Odds ratio 10.02, P = 8.6E-03)].

Reports Added
[Cadherin-13 is a critical regulator of GABAergic modulation in human stem-cell-derived neuronal networks2021]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A de novo missense variant that was predicted to be damaging was observed in the CDH13 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the CDH13 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [4 CNVs from ASD cases and 4 CNVs from SCZ cases (8 total) vs. 0 CNVs in controls (Odds ratio 10.02, P = 8.6E-03)].

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo missense variant that was predicted to be damaging was observed in the CDH13 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the CDH13 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [4 CNVs from ASD cases and 4 CNVs from SCZ cases (8 total) vs. 0 CNVs in controls (Odds ratio 10.02, P = 8.6E-03)].

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2018
icon
3

Increased from to 3

Description

A de novo missense variant that was predicted to be damaging was observed in the CDH13 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the CDH13 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [4 CNVs from ASD cases and 4 CNVs from SCZ cases (8 total) vs. 0 CNVs in controls (Odds ratio 10.02, P = 8.6E-03)].

Krishnan Probability Score

Score 0.56899037502841

Ranking 1072/25841 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 0.21759437723914

Ranking 6942/18225 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 0.18700996537969

Ranking 104/18665 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 -0.044492481143388

Ranking 10215/20870 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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