Human Gene Module / Chromosome 11 / CNTN5

CNTN5Contactin 5

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 11
Rare Variants / Common Variants
28 / 5
Aliases
CNTN5, HNB-2s,  MGC163491,  NB-2
Associated Syndromes
-
Chromosome Band
11q22.1
Associated Disorders
DD/NDD, ADHD, ID, ASD
Relevance to Autism

A paternally-inherited deletion of the CNTN5 gene co-segregated with ASD in a multiplex family with three affected male children (van Daalen et al., 2011)

Molecular Function

Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity in the cerebral cortical neurons but not in hippocampal neurons. Probably involved in neuronal activity in the auditory system

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CNTN5 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism van Daalen E , et al. (2011) Yes -
2 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
3 Support Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders Nava C , et al. (2013) Yes ID
4 Positive Association De novo mutations in epileptic encephalopathies Epi4K Consortium , et al. (2013) No IS, LGS, DD, ID, ASD, ADHD
5 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Cukier HN , et al. (2014) Yes -
6 Positive Association A candidate gene association study further corroborates involvement of contactin genes in autism Poot M (2014) Yes -
7 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 -
8 Support CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders Mercati O , et al. (2016) Yes -
9 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
10 Support - Mitani T et al. (2021) No -
11 Support - Zhou X et al. (2022) Yes -
Rare Variants   (28)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Unknown 23632794 Nava C , et al. (2013)
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
delACAC - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.287A>G p.Asp96Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2632G>A p.Ala878Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_gain Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
- - copy_number_loss Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
- - copy_number_loss Familial Paternal Multiplex 21837366 van Daalen E , et al. (2011)
c.970G>A p.Ala324Thr missense_variant De novo - - 23934111 Epi4K Consortium , et al. (2013)
c.474T>G p.Ile158Met missense_variant Familial - Unknown 27166760 Mercati O , et al. (2016)
c.1588A>G p.Ile530Val missense_variant Unknown - Unknown 27166760 Mercati O , et al. (2016)
c.2611G>C p.Ala871Pro missense_variant Unknown - Unknown 27166760 Mercati O , et al. (2016)
c.2368T>A p.Leu790Ile missense_variant Familial - Unknown 27166760 Mercati O , et al. (2016)
c.3235T>A p.Ser1079Thr missense_variant Unknown - Unknown 27166760 Mercati O , et al. (2016)
c.724G>T p.Asp242Tyr missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.760C>T p.Leu254Phe missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.1015G>A p.Gly339Ser missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.1091C>T p.Ala364Val missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.1583T>C p.Ile528Thr missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.2510G>A p.Arg837Gln missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.2651C>T p.Ala884Val missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.2696T>C p.Ile899Thr missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.2803G>A p.Val935Ile missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.460G>C p.Asp154His missense_variant Familial Both parents Simplex 34582790 Mitani T et al. (2021)
c.3194A>T p.Tyr1065Phe missense_variant Familial Maternal Unknown 27166760 Mercati O , et al. (2016)
c.2415A>C p.Glu805Asp missense_variant Familial Maternal Multiplex 27166760 Mercati O , et al. (2016)
c.2798C>T p.Ser933Phe missense_variant Familial Maternal Multiplex 27166760 Mercati O , et al. (2016)
c.2368T>A p.Leu790Ile missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
Common Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.674-15646C>T;c.452-15646C>T Allele 1, A; allele 2, G intron_variant - - - 25337070 Poot M (2014)
c.878-20611T>C;c.656-20611T>C Allele 1, G; allele 2, A intron_variant - - - 25337070 Poot M (2014)
c.56-96487G>T;c.56-121795G>T;c.56-121796G>T Allele 1, C; allele 2, A intron_variant - - - 25337070 Poot M (2014)
c.878-6106C>T;c.656-6106C>T - intron_variant - - - 25337070 Poot M (2014)
c.674-8709A>C;c.452-8709A>C C/A intron_variant - - - 25337070 Poot M (2014)
SFARI Gene score
2

Strong Candidate

CNVs affecting the CNTN5 gene have been identified in ASD cases, including a paternally-inherited deletion of the CNTN5 gene co-segregated with ASD in a multiplex family with three affected male children (PMIDs 21837366, 23275889, 23632794). Potentially damaging missense variants in CNTN5 have also been identified in ASD probands (PMIDs 23934111, 24410847). Screening for CNTN5 CNVs and SNVs in ASD cases and controls in Mercati et al., 2016 demonstrated that CNTN5 rare SNVs were enriched in ASD cases compared to controls (P=0.01). In the same report, ASD cases with CNTN5 rare variants were shown to be more prone to suffer from hyperacusis than ASD cases without such variants (P=0.03). Intronic polymorphisms in this gene also showed association with ASD in a case-control analysis of 67 ASD patients and 117 healthy controls (Poot 2014).

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.

7/1/2020
2
icon
2

Score remained at 2

Description

CNVs affecting the CNTN5 gene have been identified in ASD cases, including a paternally-inherited deletion of the CNTN5 gene co-segregated with ASD in a multiplex family with three affected male children (PMIDs 21837366, 23275889, 23632794). Potentially damaging missense variants in CNTN5 have also been identified in ASD probands (PMIDs 23934111, 24410847). Screening for CNTN5 CNVs and SNVs in ASD cases and controls in Mercati et al., 2016 demonstrated that CNTN5 rare SNVs were enriched in ASD cases compared to controls (P=0.01). In the same report, ASD cases with CNTN5 rare variants were shown to be more prone to suffer from hyperacusis than ASD cases without such variants (P=0.03). Intronic polymorphisms in this gene also showed association with ASD in a case-control analysis of 67 ASD patients and 117 healthy controls (Poot 2014).

Reports Added
[Clustering by phenotype and genome-wide association study in autism2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

CNVs affecting the CNTN5 gene have been identified in ASD cases, including a paternally-inherited deletion of the CNTN5 gene co-segregated with ASD in a multiplex family with three affected male children (PMIDs 21837366, 23275889, 23632794). Potentially damaging missense variants in CNTN5 have also been identified in ASD probands (PMIDs 23934111, 24410847). Screening for CNTN5 CNVs and SNVs in ASD cases and controls in Mercati et al., 2016 demonstrated that CNTN5 rare SNVs were enriched in ASD cases compared to controls (P=0.01). In the same report, ASD cases with CNTN5 rare variants were shown to be more prone to suffer from hyperacusis than ASD cases without such variants (P=0.03). Intronic polymorphisms in this gene also showed association with ASD in a case-control analysis of 67 ASD patients and 117 healthy controls (Poot 2014).

Reports Added
[New Scoring Scheme]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

CNVs affecting the CNTN5 gene have been identified in ASD cases, including a paternally-inherited deletion of the CNTN5 gene co-segregated with ASD in a multiplex family with three affected male children (PMIDs 21837366, 23275889, 23632794). Potentially damaging missense variants in CNTN5 have also been identified in ASD probands (PMIDs 23934111, 24410847). Screening for CNTN5 CNVs and SNVs in ASD cases and controls in Mercati et al., 2016 demonstrated that CNTN5 rare SNVs were enriched in ASD cases compared to controls (P=0.01). In the same report, ASD cases with CNTN5 rare variants were shown to be more prone to suffer from hyperacusis than ASD cases without such variants (P=0.03). Intronic polymorphisms in this gene also showed association with ASD in a case-control analysis of 67 ASD patients and 117 healthy controls (Poot 2014).

Reports Added
[Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016]
4/1/2016
icon
3

Increased from to 3

Description

CNVs affecting the CNTN5 gene have been identified in ASD cases, including a paternally-inherited deletion of the CNTN5 gene co-segregated with ASD in a multiplex family with three affected male children (PMIDs 21837366, 23275889, 23632794). Potentially damaging missense variants in CNTN5 have also been identified in ASD probands (PMIDs 23934111, 24410847). Screening for CNTN5 CNVs and SNVs in ASD cases and controls in Mercati et al., 2016 demonstrated that CNTN5 rare SNVs were enriched in ASD cases compared to controls (P=0.01). In the same report, ASD cases with CNTN5 rare variants were shown to be more prone to suffer from hyperacusis than ASD cases without such variants (P=0.03). Intronic polymorphisms in this gene also showed association with ASD in a case-control analysis of 67 ASD patients and 117 healthy controls (Poot 2014).

Reports Added
[Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.2011] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders.2013] [Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders.2014] [A candidate gene association study further corroborates involvement of contactin genes in autism.2014] [No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contacti...2015] [De novo mutations in epileptic encephalopathies.2013] [CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.2016]
Krishnan Probability Score

Score 0.49644820199256

Ranking 2597/25841 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 0.0013540614430326

Ranking 11573/18225 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 0.9433876305931

Ranking 15668/18665 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 8

Ranking 220/461 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
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