CNTNAP2
Homo sapiens
Gene Name: contactin associated protein-like 2
Aliases: CDFE; NRXN4; CASPR2; DKFZp781D1846
Chromosome No: 7
Chromosome Band: 7q35-q36.1
Genetic Category: Syndromic-Genetic Association, Rare Single Gene variant-Genetic Association-Rare Single Gene variant-Genetic association/functional-Rare single gene variant/genetic association-Genetic association/Rare single gene variant-Functional-Rare single gene variant/Functional
Associated Syndrome(s): Pitt-Hopkins like syndrome 1
Aliases: CDFE; NRXN4; CASPR2; DKFZp781D1846
Chromosome No: 7
Chromosome Band: 7q35-q36.1
Genetic Category: Syndromic-Genetic Association, Rare Single Gene variant-Genetic Association-Rare Single Gene variant-Genetic association/functional-Rare single gene variant/genetic association-Genetic association/Rare single gene variant-Functional-Rare single gene variant/Functional
Associated Syndrome(s): Pitt-Hopkins like syndrome 1
Summary Statistics:
ASD Reports: 98
Recent Reports: 18
Annotated variants: 174
Associated CNVs: 14
Evidence score: 4
ASD Reports: 98
Recent Reports: 18
Annotated variants: 174
Associated CNVs: 14
Evidence score: 4
| Associated Disorders: |
|
Relevance to Autism
Several studies have found a genetic association of the CNTNAP2 gene with autism. Among these, one study (Li et al., 2010) found positive association with the Chinese Han population. In addition, rare variants in the CNTNAP2 gene, including deletions and nonsynonymous changes, are also suggested to play a role in autism, ID, DD and language impairment. Interestingly, positive associations with CNTNAP2 and selective mutism, epilepsy and specific language impairment have also been found.
Molecular Function
This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein is localized at the juxtaparanodes of myelinated axons and associated with potassium channels.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.
ASD
Positive Association
Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder.
ASD
Positive Association
A functional genetic link between distinct developmental language disorders.
ASD
Positive Association
A candidate gene association study further corroborates involvement of contactin genes in autism.
ASD
Positive Association
Effect of CNTNAP2 polymorphism on receptive language in children with autism spectrum disorder without language developmental delay
Receptive language ability in ASD
Positive Association
Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.
ASD
Positive Association
Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach.
ASD
Positive Association
Association between Genetic Variants in DUSP15, CNTNAP2, and PCDHA Genes and Risk of Childhood Autism Spectrum Disorder
ASD
Positive Association
Defining the contribution of CNTNAP2 to autism susceptibility.
ASD
Positive Association
CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case-control study combined with a meta-analysis
ASD
Language impairment
Positive Association
Individual common variants exert weak effects on the risk for autism spectrum disorderspi.
ASD
Positive Association
Common variants of the autism-associated CNTNAP2 gene contribute to the modulatory effect of social function mediated by temporal cortex
ALTs
Gray matter volume and social performance
Positive Association
CNTNAP2 variants affect early language development in the general population.
ASD
Positive Association
Genetic variants in the CNTNAP2 gene are associated with gender differences among dyslexic children in China.
Developmental dyslexia
Positive Association
Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.
ASD
Negative Association
Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.
ASD
Negative Association
Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS dat...
ASD
Negative Association
Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders.
ASD, SCZ
BPD
Negative Association
CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.
ASD
Negative Association
No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contacti...
ASD
Support
Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells.
SCZ
Support
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.
ASD
Support
Pitt Hopkins-Like Syndrome 1 with Novel CNTNAP2 Mutation in Siblings
Pitt-Hopkins like syndrome 1, DD, epilepsy/seizure
ASD
Support
Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration.
Support
Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...
ASD
ID, epilepsy
Support
Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.
Cortical dysplasia-focal epilepsy syndrome
ID, ADHD, ASD, epilepsy/seizures
Support
Characterization of intellectual disability and autism comorbidity through gene panel sequencing.
ID, ASD or autistic traits
Support
Comprehensive molecular testing in patients with high functioning autism spectrum disorder.
ASD
Support
Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.
ASD
Support
Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants
ADHD, ID
Autistic features, stereotypy
Support
Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.
Specific language impairment
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
Novel Missense CNTNAP2 Variant Identified in Two Consanguineous Pakistani Families With Developmental Delay
DD, ID, epilepsy/seizures
ASD, stereotypy
Support
CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.
OCD
TS, ID
Support
The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children.
ASD, epilepsy/seizures
Support
Characterisation of CASPR2 deficiency disorder - a syndrome involving autism, epilepsy and language impairment.
ASD, ID, epilepsy/seizures
Support
Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case.
ASD
Support
High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population
DD, epilepsy/seizures
Support
Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task.
Support
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
ASD
Support
Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype c...
ASD
Support
Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.
ID
Epilepsy/seizures
Support
CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...
Pitt-Hopkins like syndrome 1
ID, epilepsy
Support
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
ASD, ADHD, DD, ID, epilepsy/seizures
Support
Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.
Epilepsy/seizures
Support
Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.
DD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
Both rare and common genetic variants contribute to autism in the Faroe Islands.
ASD
Support
Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome.
ID
Epilepsy
Support
Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder.
ASD
Support
Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings
ASD
Support
Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.
ASD
Support
Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...
Epilepsy
ADHD
Support
Hyperexcitable and Immature-Like Neuronal Activity in the Auditory Cortex of Adult Rats Lacking the Language-Linked CNTNAP2 Gene
Support
Genetic testing including targeted gene panel in a diverse clinical population of children with autism spectrum disorder: Findings and implications.
ASD
Support
Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.
ASD
Support
Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.
ASD
Support
Genome-wide detection of tandem DNA repeats that are expanded in autism
ASD
Support
Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and...
ID, epilepsy/seizures
Support
Rare copy number variants are an important cause of epileptic encephalopathies.
Epilepsy
ID, ASD
Support
A common variant of CNTNAP2 is associated with sub-threshold autistic traits and intellectual disability
ASD
ASD subphenotypes
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Support
Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.
CAS
Support
Cntnap2-dependent molecular networks in autism spectrum disorder revealed through an integrative multi-omics analysis
ASD
Support
CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.
SCZ
Epilepsy
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Highly Cited
Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K channels.
Recent Recommendation
CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.
Recent Recommendation
Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2.
Recent Recommendation
Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.
Recent Recommendation
Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.
Epilepsy
ASD
Recent Recommendation
Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.
CAS
Recent Recommendation
Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.
Recent Recommendation
Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...
DD
ID
Recent Recommendation
Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B.
Recent Recommendation
Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.
Recent Recommendation
Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons.
Recent Recommendation
Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS.
Recent Recommendation
Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.
ID
Recent Recommendation
Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2.
Recent Recommendation
Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.
Recent Recommendation
A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-relat...
Selective Mutism
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN051R007
missense_variant
c.2191G>A
p.Gly731Ser
Familial
Paternal
Simplex
GEN051R008
missense_variant
c.2606T>C
p.Ile869Thr
Familial
Paternal
Multiplex
GEN051R009
missense_variant
c.2606T>C
p.Ile869Thr
Familial
Maternal
Simplex
GEN051R010
missense_variant
c.2606T>C
p.Ile869Thr
Familial
Paternal
Simplex
GEN051R011
missense_variant
c.2717G>A
p.Arg906His
Familial
Paternal
Multiplex
GEN051R012
missense_variant
c.3356G>A
p.Arg1119His
Familial
Paternal
Multiplex
GEN051R013
missense_variant
c.3385G>C
p.Asp1129His
Familial
Paternal
Multiplex
GEN051R014
missense_variant
c.3679G>A
p.Ala1227Thr
Familial
Maternal & paternal
Extended multiplex
GEN051R015
missense_variant
c.3758T>C
p.Ile1253Thr
Familial
Maternal
Multiplex
GEN051R016
missense_variant
c.3833C>T
p.Thr1278Ile
Familial
Maternal
Simplex
GEN051R019
frameshift_variant
c.1175_1176dup
p.Asp393ArgfsTer51
Familial
Paternal
GEN051R030a
frameshift_variant
c.3709del
p.Asp1237IlefsTer17
Familial
Both parents
Extended multiplex
GEN051R068
missense_variant
c.3218A>T
p.Asp1073Val
Familial
Paternal
Simplex
GEN051R070a
stop_gained
c.1480G>T
p.Glu494Ter
Familial
Both parents
Simplex
GEN051R073b
frameshift_variant
c.2964del
p.Cys989AlafsTer45
Familial
Maternal
Multiplex
GEN051R075a
stop_gained
c.2046C>A
p.Cys682Ter
Familial
Both parents
Multiplex
GEN051R087a
missense_variant
c.2038G>A
p.Glu680Lys
Familial
Both parents
Simplex
GEN051R098a
frameshift_variant
c.1780_1781dup
p.Tyr595SerfsTer12
Familial
Both parents
Multiplex
GEN051R100b
frameshift_variant
c.1977_1989del13
p.Val660PhefsTer9
Familial
Maternal
Multiplex
GEN051R104a
missense_variant
c.682G>A
p.Gly228Arg
Familial
Both parents
Multiplex
GEN051R105a
missense_variant
c.682G>A
p.Gly228Arg
Familial
Both parents
Multiplex
GEN051R109a
frameshift_variant
c.1361_1362del
p.Asn454ArgfsTer24
Familial
Both parents
Multiplex
GEN051R110a
frameshift_variant
c.1361_1362del
p.Asn454ArgfsTer24
Familial
Both parents
Multiplex
GEN051R111a
frameshift_variant
c.1361_1362del
p.Asn454ArgfsTer24
Familial
Both parents
Multiplex
GEN051R112a
frameshift_variant
c.1361_1362del
p.Asn454ArgfsTer24
Familial
Both parents
Simplex
GEN051R116a
frameshift_variant
c.3407_3411del
p.Tyr1136SerfsTer27
Familial
Both parents
Simplex
GEN051R120a
frameshift_variant
c.1680del
p.Asn561IlefsTer45
Familial
Both parents
Simplex
GEN051R125
frameshift_variant
c.1628del
p.Ser543IlefsTer13
Familial
Maternal
Multiplex
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN051C002
intron_variant
rs2710102
c.2099-26267A>G;c.587-26267A>G
N/A
AGRE
Discovery
GEN051C004
intron_variant
rs2710102
c.2099-26267A>G;c.587-26267A>G
N/A
Discovery
GEN051C006
intron_variant
rs2710102
c.2099-26267A>G;c.587-26267A>G
C/T
Raine
Discovery
GEN051C007
intron_variant
rs759178
c.2099-25545A>C;c.587-25545A>C
G to T
Raine
Discovery
GEN051C008
intron_variant
rs17236239
c.2099-18352A>G;c.587-18352A>G
Raine
Discovery
GEN051C009
intron_variant
rs2538976
c.2099-14838T>C;c.587-14838T>C
G/A
Raine
Discovery
GEN051C010
intron_variant
rs2710117
c.2255+959T>A;c.743+959T>A
A/G
Raine
Discovery
GEN051C011
intron_variant
rs851715
c.2099-73751C>T;c.587-73751C>T
A/G
United Kingdom
Discovery
GEN051C012
intron_variant
rs10246256
c.2099-45850C>T;c.587-45850C>T
United Kingdom
Discovery
GEN051C013
intron_variant
rs2710102
c.2099-26267A>G;c.587-26267A>G
C/T
United Kingdom
Replication
GEN051C014
intron_variant
rs759178
c.2099-25545A>C;c.587-25545A>C
G to T
United Kingdom
Discovery
GEN051C015
intron_variant
rs1922892
c.2099-24246C>T;c.587-24246C>T
T to C
United Kingdom
Discovery
GEN051C016
intron_variant
rs2538991
c.2099-21038A>C;c.587-21038A>C
C/A
United Kingdom
Discovery
GEN051C017
intron_variant
rs17236239
c.2099-18352A>G;c.587-18352A>G
United Kingdom
Discovery
GEN051C018
intron_variant
rs2538976
c.2099-14838T>C;c.587-14838T>C
G/A
United Kingdom
Discovery
GEN051C019
intron_variant
rs4431523
c.2099-3491T>C;c.587-3491T>C
A to G
United Kingdom
Discovery
GEN051C020
intron_variant
rs2710117
c.2255+959T>A;c.743+959T>A
A/T
United Kingdom
Discovery
GEN051C021
intron_variant
rs1718101
c.97+308723T>C
Autism Genome Project (AGP)
Discovery (combined stages 1 and 2)
GEN051C022
intron_variant
rs2710093
c.2255+31322G>C;c.743+31322G>C
G/C
186 multiplex ASD families (from AGRE and NIMH) and 323 simplex ASD families (from SSC)
Discovery
GEN051C023
intron_variant
rs2253031
c.2255+31088A>G;c.743+31088A>G
187 multiplex ASD families (from AGRE and NIMH) and 323 simplex ASD families (from SSC)
Discovery
GEN051C024
2KB_upstream_variant
rs34712024
c.-876A>G
592 ASD families (492 trios, 73 duos, 27 singletons) recruited at the Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy at JW Goethe University Frankfurt/Main and at Saarland University Hospital
Discovery
GEN051C025
trinucleotide_repeat_microsatellite_feature
rs71781329
GCG[6]/GCG[7]
592 ASD families (492 trios, 73 duos, 27 singletons) recruited at the Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy at JW Goethe University Frankfurt/Main and at Saarland University Hospital
Discovery
GEN051C026
intron_variant
rs7804520
c.403-21804C>T
Allele 1, A; allele 2, G
67 ASD patients and 117 healthy controls
Discovery
GEN051C027
intron_variant
rs10262822
c.402+30643C>T
67 ASD patients and 117 healthy controls
Discovery
GEN051C028
intron_variant
rs1608628
c.403-32955T>G
A/C
67 ASD patients and 117 healthy controls
Discovery
GEN051C029
intron_variant
rs7794745
c.208+18133A>T
105 cases with high-functioning ASD (HFA), 133 controls
Replication
GEN051C030
intron_variant
rs7794745
c.208+18133A>T
210 ASD cases, 200 controls (Brazil)
Replication
GEN051C031
intron_variant
rs3779031
c.3248-4A>G
372 Chinese developmental dyslexia cases (282 male, 90 female), 354 Chinese controls (267 male, 87 female)
Discovery
GEN051C032
intron_variant, 3_prime_UTR_variant
rs987456
c.*279C>A
373 Chinese developmental dyslexia cases (282 male, 90 female), 354 Chinese controls (267 male, 87 female)
Discovery
GEN051C033
intron_variant
rs7794745
c.208+18133A>T
216 autistic children and 240 healthy volunteers from Bangladesh
Replication
GEN051C034
intron_variant
rs7794745
c.208+18133A>T
201 children with ASD and 200 healthy controls; all subjects of Han Chinese descent
Replication
GEN051C035
intron_variant
rs2710102
c.2099-26267A>G;c.587-26267A>G
N/A
67 children with autistic disorder (49 boys, 18 girls, aged 38-98 months) and 57 typically developing children (34 boys, 23 girls, aged 53-90 months) recruited from Kanazawa University and affiliated hospitals.
Replication
GEN051C036
intron_variant
rs2710102
c.2099-26267A>G;c.587-26267A>G
59 Japanese children with ASD (41 boys, 18 girls, age 40-98 months) and 57 typically-developing Japanese children (34 boys, 23 girls, age 53-90 months)
Replication
