CNTNAP3contactin associated protein-like 3
Autism Reports / Total Reports
5 / 7Rare Variants / Common Variants
8 / 0Aliases
CNTNAP3, RP11-204I2.1, CASPR3, CNTNAP3A, RP11-138L21.1, RP11-290L7.1Associated Syndromes
-Chromosome Band
9p12Associated Disorders
-Relevance to Autism
A rare mutation in the CNTNAP3 gene has been identified in a patient with Asperger syndrome (Vaags et al., 2012).
Molecular Function
The protein encoded by this gene belongs to the NCP family of cell-recognition molecules. This family represents a distinct subgroup of the neurexins. NCP proteins mediate neuron-glial interactions in vertebrates and glial-glial contact in invertebrates. The protein encoded by this gene may play a role in cell recognition within the nervous system. Alternatively spliced transcript variants encoding different isoforms have been described but their biological nature has not been determined.
External Links
SFARI Genomic Platforms
Reports related to CNTNAP3 (7 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | Rare deletions at the neurexin 3 locus in autism spectrum disorder | Vaags AK , et al. (2012) | Yes | - |
2 | Support | Caspr3-Deficient Mice Exhibit Low Motor Learning during the Early Phase of the Accelerated Rotarod Task | Hirata H , et al. (2016) | No | - |
3 | Support | Elevated mRNA expression of CASPR3 in patients with schizophrenia | Okita M , et al. (2017) | No | - |
4 | Support | Genomic Patterns of De Novo Mutation in Simplex Autism | Turner TN et al. (2017) | Yes | - |
5 | Support | The critical role of ASD-related gene CNTNAP3 in regulating synaptic development and social behavior in mice | Tong DL , et al. (2019) | Yes | - |
6 | Support | - | Alonso-Gonzalez A et al. (2021) | Yes | - |
7 | Support | - | Zhou X et al. (2022) | Yes | - |
Rare Variants (8)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.1944C>A | p.Ser648Arg | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.3655C>T | p.Arg1219Ter | stop_gained | De novo | - | Simplex | 28965761 | Turner TN et al. (2017) | |
c.1840C>G | p.Pro614Ala | missense_variant | Familial | Paternal | Simplex | 31150793 | Tong DL , et al. (2019) | |
c.2356C>T | p.Arg786Cys | missense_variant | Familial | Paternal | Simplex | 31150793 | Tong DL , et al. (2019) | |
c.2357G>A | p.Arg786His | missense_variant | Familial | Maternal | Simplex | 31150793 | Tong DL , et al. (2019) | |
c.2330C>A | p.Ala777Asp | missense_variant | De novo | - | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
c.1228G>T | p.Gly410Cys | missense_variant | Familial | Paternal | Simplex | 22209245 | Vaags AK , et al. (2012) | |
c.2765_2766insACTTGTGCTCATGAAGGAGTGGTTACTCCTGATGTTGGCTTGAGATATAAAAAGGGCTCTGTATTTGCACCAGAGCTATGAGATTT | p.Thr923LeufsTer14 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate
Variants in the CNTNAP3 gene (a paternally-inherited missense variant and a rare de novo nonsense variant) have been identified in ASD probands (Vaags et al., 2012; Turner et al., 2017). Elevated levels of CNTNAP3 mRNA were observed in leukocytes in a cohort of 100 schizophrenia patients compared to 100 age-matched controls (Okita et al., 2017). CNTNAP3-deficient mice were found to exhibit deficits in motor learning during the early phase of the accelerated rotarod task in Hirata et al., 2016. Tong et al., 2019 reported additional ASD probands with inherited missense variants in the CNTNAP3 gene; functional analysis of two of these missense variants (p.Pro614Ala and p.Arg786Cys), as well as the de novo nonsense variant originally reported in Turner et al., 2017 (p.Arg1219Ter), demonstrated loss-of-function effects on excitatory and inhibitory synapse development. Furthermore, Tong et al., 2019 showed that male Cntnap3-null mice exhibited deficits in social interaction.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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.
1/1/2021
Score remained at 2
Description
Variants in the CNTNAP3 gene (a paternally-inherited missense variant and a rare de novo nonsense variant) have been identified in ASD probands (Vaags et al., 2012; Turner et al., 2017). Elevated levels of CNTNAP3 mRNA were observed in leukocytes in a cohort of 100 schizophrenia patients compared to 100 age-matched controls (Okita et al., 2017). CNTNAP3-deficient mice were found to exhibit deficits in motor learning during the early phase of the accelerated rotarod task in Hirata et al., 2016. Tong et al., 2019 reported additional ASD probands with inherited missense variants in the CNTNAP3 gene; functional analysis of two of these missense variants (p.Pro614Ala and p.Arg786Cys), as well as the de novo nonsense variant originally reported in Turner et al., 2017 (p.Arg1219Ter), demonstrated loss-of-function effects on excitatory and inhibitory synapse development. Furthermore, Tong et al., 2019 showed that male Cntnap3-null mice exhibited deficits in social interaction.
10/1/2019
Decreased from 3 to 2
New Scoring Scheme
Description
Variants in the CNTNAP3 gene (a paternally-inherited missense variant and a rare de novo nonsense variant) have been identified in ASD probands (Vaags et al., 2012; Turner et al., 2017). Elevated levels of CNTNAP3 mRNA were observed in leukocytes in a cohort of 100 schizophrenia patients compared to 100 age-matched controls (Okita et al., 2017). CNTNAP3-deficient mice were found to exhibit deficits in motor learning during the early phase of the accelerated rotarod task in Hirata et al., 2016. Tong et al., 2019 reported additional ASD probands with inherited missense variants in the CNTNAP3 gene; functional analysis of two of these missense variants (p.Pro614Ala and p.Arg786Cys), as well as the de novo nonsense variant originally reported in Turner et al., 2017 (p.Arg1219Ter), demonstrated loss-of-function effects on excitatory and inhibitory synapse development. Furthermore, Tong et al., 2019 showed that male Cntnap3-null mice exhibited deficits in social interaction.
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 4 to 3
Description
Variants in the CNTNAP3 gene (a paternally-inherited missense variant and a rare de novo nonsense variant) have been identified in ASD probands (Vaags et al., 2012; Turner et al., 2017). Elevated levels of CNTNAP3 mRNA were observed in leukocytes in a cohort of 100 schizophrenia patients compared to 100 age-matched controls (Okita et al., 2017). CNTNAP3-deficient mice were found to exhibit deficits in motor learning during the early phase of the accelerated rotarod task in Hirata et al., 2016. Tong et al., 2019 reported additional ASD probands with inherited missense variants in the CNTNAP3 gene; functional analysis of two of these missense variants (p.Pro614Ala and p.Arg786Cys), as well as the de novo nonsense variant originally reported in Turner et al., 2017 (p.Arg1219Ter), demonstrated loss-of-function effects on excitatory and inhibitory synapse development. Furthermore, Tong et al., 2019 showed that male Cntnap3-null mice exhibited deficits in social interaction.
10/1/2018
Increased from to 4
Description
Variants in the CNTNAP3 gene (a paternally-inherited missense variant and a rare de novo nonsense variant) have been identified in ASD probands (Vaags et al., 2012; Turner et al., 2017). Elevated levels of CNTNAP3 mRNA were observed in leukocytes in a cohort of 100 schizophrenia patients compared to 100 age-matched controls (Okita et al., 2017). CNTNAP3-deficient mice were found to exhibit deficits in motor learning during the early phase of the accelerated rotarod task in Hirata et al., 2016.
Krishnan Probability Score
Score 0.49194072031139
Ranking 4893/25841 scored genes
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ExAC Score
Score 0.072566365554852
Ranking 8167/18225 scored genes
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Sanders TADA Score
Score 0.95044010135534
Ranking 18493/18665 scored genes
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Larsen Cumulative Evidence Score
Score 0
Ranking 442/461 scored genes
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