Human Gene Module / Chromosome 3 / CNTN3

CNTN3contactin 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
6 / 0
Aliases
CNTN3, BIG-1,  PANG,  PCS
Associated Syndromes
Tourette syndrome
Chromosome Band
3p12.3
Associated Disorders
-
Relevance to Autism

A rare mutation in the CNTN3 gene has been identified in a patient with ASD (Vaags et al., 2012).

Molecular Function

Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CNTN3 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Identifying autism loci and genes by tracing recent shared ancestry Morrow EM , et al. (2008) Yes -
2 Primary Rare deletions at the neurexin 3 locus in autism spectrum disorder Vaags AK , et al. (2012) Yes -
3 Support Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel Brett M , et al. (2014) Yes MCA
4 Negative Association No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins Murdoch JD , et al. (2015) Yes -
5 Positive Association De Novo Coding Variants Are Strongly Associated with Tourette Disorder Willsey AJ , et al. (2017) No -
6 Support - Woodbury-Smith M 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 Familial Both parents Simplex 18621663 Morrow EM , et al. (2008)
c.440C>T p.Pro147Leu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.2521C>T p.Arg841Trp missense_variant De novo - Simplex 28472652 Willsey AJ , et al. (2017)
c.1500A>G p.Thr500%3D synonymous_variant De novo - - 35205252 Woodbury-Smith M et al. (2022)
c.547A>T p.Ile183Leu missense_variant Familial Maternal Multiplex 24690944 Brett M , et al. (2014)
c.2600G>A p.Arg867Gln missense_variant Familial Paternal Simplex 22209245 Vaags AK , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A homozygous deletion nearest to the 5' end of the CNTN3 gene was identified in an ASD proband; an unaffected sibling and both parents (first-cousins) were hemizygous for the deletion (Morrow et al., 2008). Inherited missense variants in the CNTN3 gene have also been identified in individuals with ASD (Vaags et al., 2012; Brett et al., 2014), while a rare de novo missense variant in this gene was identified in a proband with Tourette syndrome (Willsey 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 homozygous deletion nearest to the 5' end of the CNTN3 gene was identified in an ASD proband; an unaffected sibling and both parents (first-cousins) were hemizygous for the deletion (Morrow et al., 2008). Inherited missense variants in the CNTN3 gene have also been identified in individuals with ASD (Vaags et al., 2012; Brett et al., 2014), while a rare de novo missense variant in this gene was identified in a proband with Tourette syndrome (Willsey et al., 2017).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A homozygous deletion nearest to the 5' end of the CNTN3 gene was identified in an ASD proband; an unaffected sibling and both parents (first-cousins) were hemizygous for the deletion (Morrow et al., 2008). Inherited missense variants in the CNTN3 gene have also been identified in individuals with ASD (Vaags et al., 2012; Brett et al., 2014), while a rare de novo missense variant in this gene was identified in a proband with Tourette syndrome (Willsey et al., 2017).

Reports Added
[New Scoring Scheme]
10/1/2018
icon
4

Increased from to 4

Description

A homozygous deletion nearest to the 5' end of the CNTN3 gene was identified in an ASD proband; an unaffected sibling and both parents (first-cousins) were hemizygous for the deletion (Morrow et al., 2008). Inherited missense variants in the CNTN3 gene have also been identified in individuals with ASD (Vaags et al., 2012; Brett et al., 2014), while a rare de novo missense variant in this gene was identified in a proband with Tourette syndrome (Willsey et al., 2017).

Krishnan Probability Score

Score 0.49497143062244

Ranking 3302/25841 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 0.014141786255582

Ranking 9735/18225 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 0.88550104972887

Ranking 5192/18665 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
Larsen Cumulative Evidence Score

Score 0

Ranking 440/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.41002402837347

Ranking 1348/20870 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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