Human Gene Module / Chromosome 3 / CNTN6

CNTN6Contactin 6

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
14 / 17
Rare Variants / Common Variants
56 / 4
EAGLE Score
13.8
Strong Learn More
Aliases
CNTN6, MGC133256,  NB3
Associated Syndromes
Tourette syndrome
Chromosome Band
3p26.3
Associated Disorders
ADHD
Genetic Category
Rare Single Gene Mutation, Genetic Association
Relevance to Autism

A de novo duplication of the CNTN6 gene was identified in an autistic proband from a simplex family (van Daalen et al., 2011).

Molecular Function

The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CNTN6 (17 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 Positive Association A candidate gene association study further corroborates involvement of contactin genes in autism Poot M (2014) Yes -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Support Single gene microdeletions and microduplication of 3p26.3 in three unrelated families: CNTN6 as a new candidate gene for intellectual disability Kashevarova AA , et al. (2015) Yes -
5 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 -
6 Support CNTN6 copy number variations in 14 patients: a possible candidate gene for neurodevelopmental and neuropsychiatric disorders Hu J , et al. (2015) Yes ADHD, OCD
7 Recent Recommendation CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders Mercati O , et al. (2016) Yes -
8 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
9 Support Association of Cell Adhesion Molecules Contactin-6 and Latrophilin-1 Regulates Neuronal Apoptosis Zuko A , et al. (2016) No -
10 Recent Recommendation Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome Huang AY , et al. (2017) No -
11 Support Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly Woodbury-Smith M , et al. (2017) Yes Macrocephaly
12 Support Schizophrenia and epilepsy as a result of maternally inherited CNTN6 copy number variant Juan-Perez C , et al. (2018) No -
13 Negative Association CNTN6 copy number variations: Uncertain clinical significance in individuals with neurodevelopmental disorders Repnikova EA , et al. (2019) Yes -
14 Support Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder Schmitz-Abe K et al. (2020) Yes -
15 Support - Zhou X et al. (2022) Yes -
16 Support - Chan AJS et al. (2022) Yes -
17 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (56)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - - 26257835 Hu J , et al. (2015)
- - copy_number_loss Unknown - Simplex 26257835 Hu J , et al. (2015)
- - copy_number_loss Unknown - Unknown 26257835 Hu J , et al. (2015)
G>T - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
insA - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_gain Unknown - Unknown 27166760 Mercati O , et al. (2016)
- - copy_number_gain De novo - Simplex 21837366 van Daalen E , et al. (2011)
- - copy_number_loss Familial Paternal Multiplex 26257835 Hu J , et al. (2015)
- - copy_number_gain Unknown - Multi-generational 26257835 Hu J , et al. (2015)
- - copy_number_loss Unknown - Multi-generational 26257835 Hu J , et al. (2015)
c.79A>G p.Ile27Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Unknown - Multiplex 25606055 Kashevarova AA , et al. (2015)
c.2317C>G p.Pro773Ala missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2455A>G p.Met819Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2719C>T p.Pro907Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
- - copy_number_loss Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
- - copy_number_gain Familial Paternal Unknown 27166760 Mercati O , et al. (2016)
- - copy_number_loss Familial Maternal Unknown 27166760 Mercati O , et al. (2016)
- - copy_number_loss Familial Both parents - 32820185 Schmitz-Abe K et al. (2020)
- - copy_number_loss Familial Paternal Multiplex 27166760 Mercati O , et al. (2016)
- - copy_number_gain Familial Paternal Simplex 25606055 Kashevarova AA , et al. (2015)
- - copy_number_loss Familial Paternal Simplex 25606055 Kashevarova AA , et al. (2015)
- - copy_number_gain Familial Maternal Multi-generational 26257835 Hu J , et al. (2015)
- - copy_number_gain Familial Paternal Multi-generational 26257835 Hu J , et al. (2015)
c.908G>A p.Arg303Gln missense_variant Familial - Unknown 27166760 Mercati O , et al. (2016)
c.1288G>A p.Gly430Arg missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2309C>T p.Pro770Leu missense_variant De novo - Multiplex 27166760 Mercati O , et al. (2016)
- - copy_number_loss Familial Maternal Multi-generational 29983269 Juan-Perez C , et al. (2018)
c.2768G>A p.Trp923Ter stop_gained Familial Maternal Multiplex 27166760 Mercati O , et al. (2016)
c.170C>T p.Ser57Leu missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.908G>A p.Arg303Gln missense_variant Familial Unknown Simplex 27166760 Mercati O , et al. (2016)
c.325A>G p.Ile109Val missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.449T>C p.Phe150Ser missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.908G>A p.Arg303Gln missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.908G>A p.Arg303Gln missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.928G>A p.Gly310Ser missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.1253dup p.Ser419ValfsTer33 frameshift_variant Familial Maternal - 36309498 Chan AJS et al. (2022)
c.1001A>C p.Asn334Thr missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.1256C>G p.Ser419Cys missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.1585A>C p.Ile529Leu missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.2308C>T p.Pro770Ser missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.2480C>T p.Ala827Val missense_variant Familial Paternal Simplex 27166760 Mercati O , et al. (2016)
c.2873C>T p.Thr958Ile missense_variant Familial Maternal Simplex 27166760 Mercati O , et al. (2016)
c.2983T>A p.Ser995Thr missense_variant Familial Paternal Unknown 27166760 Mercati O , et al. (2016)
c.112C>G p.Pro38Ala missense_variant Familial Paternal Multiplex 27166760 Mercati O , et al. (2016)
c.928G>A p.Gly310Ser missense_variant Familial Maternal Multiplex 27166760 Mercati O , et al. (2016)
c.1585A>C p.Ile529Leu missense_variant Familial Paternal Multiplex 27166760 Mercati O , et al. (2016)
c.2048T>G p.Ile683Ser missense_variant Familial Paternal Multiplex 27166760 Mercati O , et al. (2016)
c.2573G>A p.Ser858Asn missense_variant Familial Paternal Multiplex 27166760 Mercati O , et al. (2016)
c.908G>A p.Arg303Gln missense_variant Familial Maternal Simplex 30836150 Repnikova EA , et al. (2019)
c.2234C>T p.Ser745Leu missense_variant Familial Paternal Simplex 30836150 Repnikova EA , et al. (2019)
c.908G>A p.Arg303Gln missense_variant Familial Maternal Multiplex 30836150 Repnikova EA , et al. (2019)
c.908G>A p.Arg303Gln missense_variant Familial Both parents Multiplex 27166760 Mercati O , et al. (2016)
c.1735G>C p.Val579Leu missense_variant Familial Paternal Multiplex 30836150 Repnikova EA , et al. (2019)
c.2869_2870del p.Asn957TyrfsTer4 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-83+8620T>G;c.-162+8620T>G;c.-83+8611T>G;c.-194+8620T>G C/A intron_variant - - - 25337070 Poot M (2014)
c.-83+19755A>G;c.-162+19755A>G;c.-83+19746A>G;c.-193-15392A>G - intron_variant - - - 25337070 Poot M (2014)
c.-83+27237G>A;c.-162+27237G>A;c.-83+27228G>A;c.-193-7910G>A G/A intron_variant - - - 25337070 Poot M (2014)
c.-83+12397A>G;c.-162+12397A>G;c.-83+12388A>G;c.-194+12397A>G Allele 1, G; allele 2, A intron_variant - - - 25337070 Poot M (2014)
SFARI Gene score
2

Strong Candidate

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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 CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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
[Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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]
4/1/2019
3
icon
3

Decreased from 3 to 3

Description

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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
[CNTN6 copy number variations: Uncertain clinical significance in individuals with neurodevelopmental disorders.2019]
7/1/2018
3
icon
3

Decreased from 3 to 3

Description

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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
[Schizophrenia and epilepsy as a result of maternally inherited CNTN6 copy number variant.2018]
10/1/2017
3
icon
3

Decreased from 3 to 3

Description

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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 RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly.2017]
7/1/2017
3
icon
3

Decreased from 3 to 3

Description

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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
[Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.2017]
1/1/2017
3
icon
3

Decreased from 3 to 3

Description

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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
[Association of Cell Adhesion Molecules Contactin-6 and Latrophilin-1 Regulates Neuronal Apoptosis.2016]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

CNVs affecting the CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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 CNTN6 gene have been identified in probands with ASD and other neurodevelopmental disorders (PMIDs 21837366, 25606055, 26257835). A de novo potentially damaging missense variant in CNTN6 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); however, this variant was also present in dbSNP and ESP. Screening for CNTN6 CNVs and SNVs in ASD cases and controls demonstrated that CNTN6 deletions (6/1534 cases vs. 1/8936 controls; P=0.00006) and CNTN6 rare SNVs (18/501 cases vs. 535/33480 controls; P=0.005) were enriched in ASD cases (Mercati et al., 2016); among the rare CNTN6 variants identified were two deletions transmitted by fathers diagnosed with ASD, a nonsense variant transmitted by a mother to two sons with ASD, a de novo missense variant in a boy with ASD, and three missense variants shown experimentally to affect the promoting effect of CNTN6 on neuritogenesis. In the same report, ASD cases with CNTN6 rare variants were shown to be more prone to display negative responses to specific sensory stimuli than ASD cases without such variants (P=0.0009). 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 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] [Single gene microdeletions and microduplication of 3p26.3 in three unrelated families: CNTN6 as a new candidate gene for intellectual disability.2015] [CNTN6 copy number variations in 14 patients: a possible candidate gene for neurodevelopmental and neuropsychiatric disorders.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.2016]
Krishnan Probability Score

Score 0.54264547746319

Ranking 1424/25841 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 3.5867113517389E-22

Ranking 18041/18225 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 0.83347683426039

Ranking 2944/18665 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 441/461 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 0.29549934794033

Ranking 2810/20870 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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