CNTNAP2contactin associated protein-like 2

SFARI Gene Score

Strong Candidate, Syndromic Criteria 2.1, Syndromic

Autism Reports / Total Reports

58 / 101

Rare Variants / Common Variants

133 / 36

Aliases

CNTNAP2, CDFE, NRXN4, CASPR2, DKFZp781D1846

Associated Syndromes

Cortical dysplasia-focal epilepsy syndrome, Pitt-Hopkins like syndrome 1, Pitt-Hopkins like syndrome 1, DD, epilepsy/seizure

Chromosome Band

7q35-q36.1

Associated Disorders

ADHD, ID, EP, BPD, EPS, ASD

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.

SFARI Genomic Platforms

GPF browser SFARI genome browser

Reports (101)
Variants (169)
Gene Score
Protein Interactions (19)

Reports related to CNTNAP2 (101 Reports)

#	Type	Title	Author, Year	Autism Report	Associated Disorders
1	Highly Cited	Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels	Poliak S , et al. (2000)	No	-
2	Support	CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder	Verkerk AJ , et al. (2003)	No	TS, ID
3	Support	Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2	Strauss KA , et al. (2006)	No	ID, ADHD, ASD, epilepsy/seizures
4	Support	CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy	Friedman JI , et al. (2007)	No	Epilepsy
5	Positive Association	Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene	Alarcn M , et al. (2008)	Yes	-
6	Primary	A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism	Arking DE , et al. (2008)	Yes	-
7	Support	Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders	Bakkaloglu B , et al. (2008)	Yes	-
8	Positive Association	A functional genetic link between distinct developmental language disorders	Vernes SC , et al. (2008)	Yes	-
9	Recent Recommendation	Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons	Horresh I , et al. (2008)	No	-
10	Recent Recommendation	Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS	Oiso S , et al. (2009)	No	-
11	Support	Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder	Poot M , et al. (2009)	Yes	-
12	Support	CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila	Zweier C , et al. (2009)	No	ID, epilepsy
13	Recent Recommendation	Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B	Horresh I , et al. (2010)	No	-
14	Recent Recommendation	Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2	Tan GC , et al. (2010)	No	-
15	Positive Association	Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population	Li X , et al. (2010)	Yes	-
16	Recent Recommendation	Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies	Mefford HC , et al. (2010)	No	ASD
17	Recent Recommendation	Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2	Scott-Van Zeeland AA , et al. (2010)	No	-
18	Support	Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case	Petrin AL , et al. (2010)	Yes	-
19	Recent Recommendation	A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-related traits	Stein MB , et al. (2011)	No	-
20	Positive Association	CNTNAP2 variants affect early language development in the general population	Whitehouse AJ , et al. (2011)	Yes	-
21	Support	Reduced transcript expression of genes affected by inherited and de novo CNVs in autism	Nord AS , et al. (2011)	Yes	-
22	Support	Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations	O'Roak BJ , et al. (2011)	Yes	-
23	Recent Recommendation	Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1	Gregor A , et al. (2011)	No	-
24	Recent Recommendation	Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits	Peagarikano O , et al. (2011)	No	-
25	Recent Recommendation	Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders	Mikhail FM , et al. (2011)	No	ID
26	Support	Rare copy number variants are an important cause of epileptic encephalopathies	Mefford HC , et al. (2011)	No	ID, ASD
27	Support	Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism	Lesca G , et al. (2012)	No	ADHD
28	Recent Recommendation	Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization	Laffin JJ , et al. (2012)	No	-
29	Positive Association	Individual common variants exert weak effects on the risk for autism spectrum disorders	Anney R , et al. (2012)	Yes	-
30	Recent Recommendation	Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development	Anderson GR , et al. (2012)	No	-
31	Support	Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay	Al-Murrani A , et al. (2012)	No	-
32	Support	A discovery resource of rare copy number variations in individuals with autism spectrum disorder	Prasad A , et al. (2013)	Yes	-
33	Negative Association	Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2	Toma C , et al. (2013)	Yes	-
34	Support	Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder	Girirajan S , et al. (2013)	Yes	-
35	Recent Recommendation	CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study	Clemm von Hohenberg C , et al. (2013)	No	-
36	Support	Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder	Koshimizu E , et al. (2013)	Yes	ID, epilepsy
37	Support	Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech	Worthey EA , et al. (2013)	No	-
38	Positive Association	Defining the contribution of CNTNAP2 to autism susceptibility	Sampath S , et al. (2013)	Yes	-
39	Support	Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families	Egger G , et al. (2014)	Yes	-
40	Support	Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome	Watson CM , et al. (2014)	No	Epilepsy
41	Positive Association	Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach	Chiocchetti AG , et al. (2014)	Yes	-
42	Positive Association	A candidate gene association study further corroborates involvement of contactin genes in autism	Poot M (2014)	Yes	-
43	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	-
44	Support	Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease	Karaca E , et al. (2015)	No	Epilepsy/seizures
45	Negative Association	CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches	Werling AM , et al. (2015)	Yes	-
46	Recent Recommendation	Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2	Hoffman EJ , et al. (2016)	No	-
47	Support	Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment	Rodenas-Cuadrado P , et al. (2016)	Yes	-
48	Support	Comprehensive molecular testing in patients with high functioning autism spectrum disorder	Alvarez-Mora MI , et al. (2016)	Yes	-
49	Positive Association	Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder	Nascimento PP , et al. (2016)	Yes	-
50	Support	Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells	Lee IS , et al. (2016)	No	-
51	Support	Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and phenotypic spectrum	Smogavec M , et al. (2016)	No	-
52	Support	Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior	Doan RN , et al. (2016)	Yes	-
53	Support	Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes	Parrini E , et al. (2016)	No	-
54	Support	Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task	Zhu B , et al. (2016)	No	-
55	Support	Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment	Chen XS , et al. (2017)	No	-
56	Support	Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration	Ross LA , et al. (2017)	No	-
57	Support	Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders	Li J , et al. (2017)	Yes	-
58	Support	Genetic testing including targeted gene panel in a diverse clinical population of children with autism spectrum disorder: Findings and implications	Kalsner L , et al. (2017)	Yes	-
59	Recent Recommendation	Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons	Canali G , et al. (2018)	No	-
60	Positive Association	Genetic variants in the CNTNAP2 gene are associated with gender differences among dyslexic children in China	Gu H , et al. (2018)	No	-
61	Negative Association	Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders	Toma C , et al. (2018)	Yes	BPD
62	Support	Both rare and common genetic variants contribute to autism in the Faroe Islands	Leblond CS , et al. (2019)	Yes	-
63	Negative Association	Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium	Zhang T , et al. (2019)	Yes	-
64	Support	Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations	Zhou WZ , et al. (2019)	Yes	-
65	Support	The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children	Long S , et al. (2019)	Yes	-
66	Support	Characterization of intellectual disability and autism comorbidity through gene panel sequencing	Aspromonte MC , et al. (2019)	Yes	-
67	Support	Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes	Feliciano P et al. (2019)	Yes	-
68	Support	Genome-wide detection of tandem DNA repeats that are expanded in autism	Trost B et al. (2020)	Yes	-
69	Support	-	Ohashi K et al. (2021)	Yes	-
70	Positive Association	-	Li D et al. (2021)	No	Gray matter volume and social performance
71	Positive Association	-	Uddin MS et al. (2021)	Yes	Language impairment
72	Positive Association	-	Fang F et al. (2021)	Yes	-
73	Support	-	Pode-Shakked B et al. (2021)	Yes	-
74	Support	-	Mitani T et al. (2021)	No	-
75	Support	-	Scala M et al. (2021)	No	Autistic features, stereotypy
76	Support	-	Mittal R et al. (2021)	No	ASD
77	Support	-	Shiota Y et al. (2021)	Yes	ASD subphenotypes
78	Support	-	Scott KE et al. (2022)	No	-
79	Support	-	Woodbury-Smith M et al. (2022)	Yes	-
80	Support	-	Lithuania) (04/0)	Yes	-
81	Positive Association	-	Shiota Y et al. (2022)	Yes	-
82	Support	-	Badshah N et al. (2022)	No	ASD, stereotypy
83	Support	-	Zhou X et al. (2022)	Yes	-
84	Support	-	Jang WE et al. (2022)	Yes	-
85	Support	-	Mhrle D et al. (2023)	Yes	-
86	Support	-	Cifuentes-Diaz C et al. (2023)	No	-
87	Recent Recommendation	-	Weinschutz Mendes H et al. (2023)	Yes	-
88	Support	-	Spataro N et al. (2023)	Yes	-
89	Support	-	Haddad FL et al. (2023)	Yes	-
90	Support	-	St George-Hyslop F et al. (2023)	No	-
91	Recent Recommendation	-	D&#x27 et al. (2023)	No	ASD, ADHD
92	Support	-	Zhang J et al. (2023)	Yes	-
93	Support	-	Cirnigliaro M et al. (2023)	Yes	-
94	Support	-	Sheth F et al. (2023)	Yes	DD, ID
95	Support	-	Dawson MS et al. (2023)	Yes	-
96	Support	-	Alaa El-Cheikh Mohamad et al. (2023)	Yes	-
97	Support	-	Manish Kumar Tripathi et al. (2024)	Yes	-
98	Recent Recommendation	-	Qing Zhang et al. (2024)	Yes	-
99	Support	-	Alice Zheng et al. (2024)	Yes	-
100	Support	-	Mathieu Thabault et al. (2024)	Yes	-
101	Support	-	Axel Schmidt et al. (2024)	No	-

Rare Variants (133)

Allele Change	Residue Change	Variant Type	Inheritance Pattern	Parental Transmission	Family Type	PubMed ID	Author, Year
-	-	copy_number_loss	-	-	-	22031302	Mikhail FM , et al. (2011)
-	-	copy_number_loss	Unknown	-	-	24643514	Egger G , et al. (2014)
-	-	copy_number_loss	De novo	-	-	21827697	Gregor A , et al. (2011)
-	-	minisatellite	Unknown	-	Simplex	32717741	Trost B et al. (2020)
-	-	minisatellite	Unknown	-	Unknown	32717741	Trost B et al. (2020)
T>C	-	intergenic_variant	-	-	Unknown	27667684	Doan RN , et al. (2016)
-	-	copy_number_gain	Unknown	-	Unknown	23275889	Prasad A , et al. (2013)
-	-	copy_number_loss	Familial	Maternal	-	21448237	Nord AS , et al. (2011)
c.2153G>A	p.Trp718Ter	stop_gained	-	-	-	21827697	Gregor A , et al. (2011)
-	-	copy_number_loss	Unknown	-	Simplex	21108403	Petrin AL , et al. (2010)
-	-	copy_number_loss	Unknown	-	Simplex	22766611	Laffin JJ , et al. (2012)
-	-	copy_number_loss	Familial	Maternal	-	21827697	Gregor A , et al. (2011)
-	-	copy_number_gain	Familial	Paternal	Simplex	35454361	Lithuania) (04/0)
-	-	copy_number_loss	Unknown	-	Simplex	17646849	Friedman JI , et al. (2007)
c.98-119906del	-	intron_variant	-	-	Unknown	27667684	Doan RN , et al. (2016)
-	-	copy_number_loss	Familial	Paternal	-	20502679	Mefford HC , et al. (2010)
-	-	copy_number_loss	Familial	Maternal	Simplex	37183190	D&#x27 et al. (2023)
-	-	copy_number_loss	Familial	Paternal	Simplex	37183190	D&#x27 et al. (2023)
c.1778-1G>C	-	splice_site_variant	De novo	-	-	30763456	Zhou WZ , et al. (2019)
-	-	copy_number_loss	Familial	Paternal	Simplex	26985448	Lee IS , et al. (2016)
-	-	copy_number_gain	Familial	Maternal	Unknown	22738016	Lesca G , et al. (2012)
c.655T>A	p.Ser219Thr	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
-	-	copy_number_loss	Familial	Maternal	Simplex	19896112	Zweier C , et al. (2009)
-	-	copy_number_loss	Familial	Paternal	Multiplex	34778490	Mittal R et al. (2021)
c.694C>T	p.Gln232Ter	stop_gained	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.1220A>G	p.Asn407Ser	missense_variant	-	-	-	18179895	Bakkaloglu B , et al. (2008)
c.1252A>G	p.Asn418Asp	missense_variant	-	-	-	18179895	Bakkaloglu B , et al. (2008)
c.2147A>G	p.Tyr716Cys	missense_variant	-	-	-	18179895	Bakkaloglu B , et al. (2008)
c.3862C>T	p.Arg1288Cys	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
-	-	complex_structural_alteration	De novo	-	Simplex	19582487	Poot M , et al. (2009)
-	-	copy_number_loss	Familial	Paternal	Multiplex	18179893	Alarcn M , et al. (2008)
c.3058C>T	p.Gln1020Ter	stop_gained	De novo	-	-	31452935	Feliciano P et al. (2019)
-	-	copy_number_gain	Familial	Maternal	Simplex	27439707	Smogavec M , et al. (2016)
-	-	copy_number_loss	Familial	Maternal	Simplex	27439707	Smogavec M , et al. (2016)
-	-	copy_number_loss	Familial	Paternal	Simplex	27439707	Smogavec M , et al. (2016)
-	-	copy_number_gain	Familial	Maternal	Simplex	23375656	Girirajan S , et al. (2013)
-	-	copy_number_loss	Familial	Paternal	Simplex	23375656	Girirajan S , et al. (2013)
c.1777+2T>C	-	splice_site_variant	-	Both parents	-	27864847	Parrini E , et al. (2016)
-	-	copy_number_loss	Familial	Paternal	Multiplex	27439707	Smogavec M , et al. (2016)
c.152C>G	p.Ser51Cys	missense_variant	Familial	-	Simplex	28831199	Li J , et al. (2017)
-	-	copy_number_loss	Familial	Both parents	Multiplex	19896112	Zweier C , et al. (2009)
-	-	copy_number_loss	Familial	Both parents	Multiplex	26539891	Karaca E , et al. (2015)
-	-	copy_number_loss	Familial	Maternal	Multiplex	23074684	Al-Murrani A , et al. (2012)
c.653C>T	p.Thr218Met	missense_variant	Familial	-	Simplex	28831199	Li J , et al. (2017)
c.686_688del	p.Glu229del	inframe_deletion	De novo	-	-	36980980	Spataro N et al. (2023)
c.1679C>G	p.Pro560Arg	missense_variant	Familial	-	Simplex	28831199	Li J , et al. (2017)
c.2396A>G	p.Asn799Ser	missense_variant	Familial	-	Simplex	28831199	Li J , et al. (2017)
c.2797T>C	p.Phe933Leu	missense_variant	Familial	-	Simplex	28831199	Li J , et al. (2017)
-	-	copy_number_loss	Familial	Both parents	Multiplex	22190369	Mefford HC , et al. (2011)
c.3814A>T	p.Ile1272Phe	missense_variant	De novo	-	Simplex	37183190	D&#x27 et al. (2023)
c.98-?_402+?	-	copy_number_loss	Familial	Maternal	Simplex	37183190	D&#x27 et al. (2023)
c.1634C>T	p.Ala545Val	missense_variant	De novo	-	Simplex	37543562	Sheth F et al. (2023)
c.252G>A	p.Trp84Ter	stop_gained	Familial	Maternal	Simplex	37183190	D&#x27 et al. (2023)
c.98-?_1348+?	-	copy_number_loss	Familial	Paternal	Simplex	37183190	D&#x27 et al. (2023)
c.3599C>T	p.Ser1200Leu	missense_variant	Unknown	-	-	31209962	Aspromonte MC , et al. (2019)
c.622C>A	p.Leu208Met	missense_variant	Unknown	-	-	35205252	Woodbury-Smith M et al. (2022)
c.515T>C	p.Ile172Thr	missense_variant	Familial	Maternal	-	33590427	Ohashi K et al. (2021)
c.158C>G	p.Ser53Cys	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.3716-7_3716-6insTGT	-	intron_variant	Unknown	-	Unknown	24083349	Worthey EA , et al. (2013)
c.511C>T	p.Arg171Cys	missense_variant	Unknown	-	Unknown	24083349	Worthey EA , et al. (2013)
c.338A>G	p.Tyr113Cys	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.416A>G	p.Asn139Ser	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.824A>G	p.His275Arg	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.860G>A	p.Ser287Asn	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.963C>A	p.Phe321Leu	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.98-7770_402+42260del	p.?	copy_number_loss	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.3331C>T	p.Gln1111Ter	stop_gained	Familial	Paternal	Simplex	37183190	D&#x27 et al. (2023)
c.97+?_209-?dup	-	copy_number_gain	Familial	Maternal	Simplex	34641913	Scala M et al. (2021)
IVS10-1G>T	-	splice_site_variant	Familial	Paternal	Simplex	19896112	Zweier C , et al. (2009)
c.853G>C	p.Gly285Arg	missense_variant	Familial	Paternal	-	29271092	Kalsner L , et al. (2017)
c.1051G>A	p.Ala351Thr	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.2123T>C	p.Val708Ala	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.2205C>A	p.Asn735Lys	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.2288A>G	p.Asp763Gly	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.2476T>G	p.Tyr826Asp	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.2657C>T	p.Thr886Ile	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.2698C>T	p.Arg900Trp	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.2820G>A	p.Leu940%3D	synonymous_variant	Unknown	-	-	35205252	Woodbury-Smith M et al. (2022)
c.1083G>A	p.Val361=	splice_site_variant	Familial	Maternal	-	21827697	Gregor A , et al. (2011)
c.1083G>A	p.Val361=	splice_site_variant	Familial	Paternal	-	21827697	Gregor A , et al. (2011)
c.3080G>C	p.Arg1027Thr	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.3131C>T	p.Pro1044Leu	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.3305T>C	p.Val1102Ala	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.3470T>C	p.Val1157Ala	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.3674C>T	p.Ser1225Leu	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.3758T>C	p.Ile1253Thr	missense_variant	Unknown	-	Simplex	25621974	Murdoch JD , et al. (2015)
c.1276C>A	p.Leu426Ile	missense_variant	Unknown	-	Unknown	24066114	Koshimizu E , et al. (2013)
c.1448G>A	p.Arg483Gln	missense_variant	Unknown	-	Unknown	24066114	Koshimizu E , et al. (2013)
c.2151C>A	p.Tyr717Ter	stop_gained	Familial	Both parents	Simplex	37183190	D&#x27 et al. (2023)
c.400T>G	p.Trp134Gly	missense_variant	Familial	Maternal	Simplex	37183190	D&#x27 et al. (2023)
c.550+5G>T	-	splice_site_variant	Familial	Both parents	Multiplex	37183190	D&#x27 et al. (2023)
-	-	copy_number_loss	Familial	Both parents	Extended multiplex	25045150	Watson CM , et al. (2014)
-	-	copy_number_loss	Familial	Both parents	Multiplex	26843181	Rodenas-Cuadrado P , et al. (2016)
c.3262C>T	p.Arg1088Ter	stop_gained	Familial	Both parents	Simplex	37183190	D&#x27 et al. (2023)
c.2449G>A	p.Gly817Arg	missense_variant	Familial	Paternal	Simplex	37183190	D&#x27 et al. (2023)
c.1777+2T>C	-	splice_site_variant	Familial	Both parents	Multiplex	37183190	D&#x27 et al. (2023)
-	-	complex_structural_alteration	Familial	Paternal	Multiplex	12809671	Verkerk AJ , et al. (2003)
c.2151C>A	p.Tyr717Ter	stop_gained	Familial	Both parents	-	34580403	Pode-Shakked B et al. (2021)
c.3046C>T	p.Arg1016Ter	stop_gained	Familial	Both parents	Unknown	31139143	Long S , et al. (2019)
c.3046C>T	p.Arg1016Ter	stop_gained	Familial	Maternal	Simplex	27439707	Smogavec M , et al. (2016)
c.1249G>T	p.Asp417Tyr	missense_variant	Familial	Maternal	-	31209962	Aspromonte MC , et al. (2019)
c.3262C>T	p.Arg1088Ter	stop_gained	Familial	Both parents	Multiplex	37183190	D&#x27 et al. (2023)
c.2752C> T	p.Leu918Phe	missense_variant	Familial	Paternal	Simplex	34641913	Scala M et al. (2021)
c.403-1G>A	-	splice_site_variant	Familial	Maternal	Multiplex	37506195	Cirnigliaro M et al. (2023)
c.-215G>A	-	2KB_upstream_variant	Familial	Paternal	Simplex	25224256	Chiocchetti AG , et al. (2014)
c.824A>G	p.His275Arg	missense_variant	Familial	Maternal	Simplex	21572417	O'Roak BJ , et al. (2011)
c.1105G>T	p.Val369Leu	missense_variant	Familial	Paternal	Multiplex	28440294	Chen XS , et al. (2017)
c.1480G>T	p.Glu494Ter	stop_gained	Familial	Both parents	Simplex	27439707	Smogavec M , et al. (2016)
-	-	copy_number_loss	Familial	Maternal and Paternal	Extended multiplex	30586385	Toma C , et al. (2018)
c.2046C>A	p.Cys682Ter	stop_gained	Familial	Both parents	Multiplex	27439707	Smogavec M , et al. (2016)
c.2191G>A	p.Gly731Ser	missense_variant	Familial	Paternal	Simplex	18179895	Bakkaloglu B , et al. (2008)
c.2606T>C	p.Ile869Thr	missense_variant	Familial	Maternal	Simplex	18179895	Bakkaloglu B , et al. (2008)
c.2606T>C	p.Ile869Thr	missense_variant	Familial	Paternal	Simplex	18179895	Bakkaloglu B , et al. (2008)
c.682G>A	p.Gly228Arg	missense_variant	Familial	Both parents	Multiplex	35911904	Badshah N et al. (2022)
c.3833C>T	p.Thr1278Ile	missense_variant	Familial	Maternal	Simplex	18179895	Bakkaloglu B , et al. (2008)
c.2038G>A	p.Glu680Lys	missense_variant	Familial	Both parents	Simplex	30675382	Leblond CS , et al. (2019)
c.2606T>C	p.Ile869Thr	missense_variant	Familial	Paternal	Multiplex	18179895	Bakkaloglu B , et al. (2008)
c.2717G>A	p.Arg906His	missense_variant	Familial	Paternal	Multiplex	18179895	Bakkaloglu B , et al. (2008)
c.1175_1176dup	p.Asp393ArgfsTer51	frameshift_variant	Familial	Paternal	-	21827697	Gregor A , et al. (2011)
c.3356G>A	p.Arg1119His	missense_variant	Familial	Paternal	Multiplex	18179895	Bakkaloglu B , et al. (2008)
c.3385G>C	p.Asp1129His	missense_variant	Familial	Paternal	Multiplex	18179895	Bakkaloglu B , et al. (2008)
c.3758T>C	p.Ile1253Thr	missense_variant	Familial	Maternal	Multiplex	18179895	Bakkaloglu B , et al. (2008)
c.1628del	p.Ser543IlefsTer13	frameshift_variant	Familial	Maternal	Multiplex	37183190	D&#x27 et al. (2023)
c.3218A>T	p.Asp1073Val	missense_variant	Familial	Paternal	Simplex	26845707	Alvarez-Mora MI , et al. (2016)
c.1680del	p.Asn561IlefsTer45	frameshift_variant	Familial	Both parents	Simplex	37183190	D&#x27 et al. (2023)
c.2964del	p.Cys989AlafsTer45	frameshift_variant	Familial	Maternal	Multiplex	27439707	Smogavec M , et al. (2016)
c.1361_1362del	p.Asn454ArgfsTer24	frameshift_variant	Familial	Both parents	Simplex	37183190	D&#x27 et al. (2023)
c.3407_3411del	p.Tyr1136SerfsTer27	frameshift_variant	Familial	Both parents	Simplex	37183190	D&#x27 et al. (2023)
c.1977_1989del13	p.Val660PhefsTer9	frameshift_variant	Familial	Maternal	Multiplex	34778490	Mittal R et al. (2021)
c.1361_1362del	p.Asn454ArgfsTer24	frameshift_variant	Familial	Both parents	Multiplex	37183190	D&#x27 et al. (2023)
c.1780_1781dup	p.Tyr595SerfsTer12	frameshift_variant	Familial	Both parents	Multiplex	34582790	Mitani T et al. (2021)
c.3709del	p.Asp1237IlefsTer17	frameshift_variant	Familial	Both parents	Extended multiplex	16571880	Strauss KA , et al. (2006)
c.3679G>A	p.Ala1227Thr	missense_variant	Familial	Maternal & paternal	Extended multiplex	18179895	Bakkaloglu B , et al. (2008)

Common Variants (36)

Allele Change	Residue Change	Variant Type	Inheritance Pattern	Paternal Transmission	Family Type	PubMed ID	Author, Year
GCG[6]/GCG[7]	-	trinucleotide_repeat_microsatellite_feature	-	-	-	25224256	Chiocchetti AG , et al. (2014)
c.402+30643C>T	-	intron_variant	-	-	-	25337070	Poot M (2014)
c.403-32955T>G	A/C	intron_variant	-	-	-	25337070	Poot M (2014)
c.3248-4A>G	-	intron_variant	-	-	-	30017804	Gu H , et al. (2018)
c.1348+50804A>G	-	intron_variant	-	-	-	20414140	Li X , et al. (2010)
c.208+18133A>T	-	intron_variant	-	-	-	34257739	Fang F et al. (2021)
c.97+308723T>C	-	intron_variant	-	-	-	22843504	Anney R , et al. (2012)
c.208+18133A>T	-	intron_variant	-	-	-	33950402	Uddin MS et al. (2021)
c.208+18133A>T	-	intron_variant	-	-	-	18179894	Arking DE , et al. (2008)
c.208+18133A>T	-	intron_variant	-	-	-	26559825	Werling AM , et al. (2015)
c.208+18133A>T	-	intron_variant	-	-	-	26909962	Nascimento PP , et al. (2016)
c.-876A>G	-	2KB_upstream_variant	-	-	-	25224256	Chiocchetti AG , et al. (2014)
c.1349-83693C>T	G/A	intron_variant	-	-	-	21310003	Whitehouse AJ , et al. (2011)
c.*279C>A	-	intron_variant, 3_prime_UTR_variant	-	-	-	30017804	Gu H , et al. (2018)
c.403-21804C>T	Allele 1, A; allele 2, G	intron_variant	-	-	-	25337070	Poot M (2014)
c.2099-26267A>G;c.587-26267A>G	-	intron_variant	-	-	-	35733350	Shiota Y et al. (2022)
c.2255+959T>A;c.743+959T>A	A/T	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-18352A>G;c.587-18352A>G	-	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-45850C>T;c.587-45850C>T	-	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2255+31088A>G;c.743+31088A>G	-	intron_variant	-	-	-	24147096	Sampath S , et al. (2013)
c.2099-26267A>G;c.587-26267A>G	N/A	intron_variant	-	-	-	34898614	Shiota Y et al. (2021)
c.2099-26267A>G;c.587-26267A>G	N/A	intron_variant	-	-	-	18179893	Alarcn M , et al. (2008)
c.2099-26267A>G;c.587-26267A>G	N/A	intron_variant	-	-	-	21193173	Stein MB , et al. (2011)
c.2099-14838T>C;c.587-14838T>C	G/A	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-21038A>C;c.587-21038A>C	C/A	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-26267A>G;c.587-26267A>G	C/T	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-73751C>T;c.587-73751C>T	A/G	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2255+31322G>C;c.743+31322G>C	G/C	intron_variant	-	-	-	24147096	Sampath S , et al. (2013)
c.2255+959T>A;c.743+959T>A	A/G	intron_variant	-	-	-	21310003	Whitehouse AJ , et al. (2011)
c.2099-3491T>C;c.587-3491T>C	A to G	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-18352A>G;c.587-18352A>G	-	intron_variant	-	-	-	21310003	Whitehouse AJ , et al. (2011)
c.2099-24246C>T;c.587-24246C>T	T to C	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-25545A>C;c.587-25545A>C	G to T	intron_variant	-	-	-	18987363	Vernes SC , et al. (2008)
c.2099-14838T>C;c.587-14838T>C	G/A	intron_variant	-	-	-	21310003	Whitehouse AJ , et al. (2011)
c.2099-26267A>G;c.587-26267A>G	C/T	intron_variant	-	-	-	21310003	Whitehouse AJ , et al. (2011)
c.2099-25545A>C;c.587-25545A>C	G to T	intron_variant	-	-	-	21310003	Whitehouse AJ , et al. (2011)

Current Score
Scoring History
3rd Party Scoring

SFARI Gene score

Strong Candidate, Syndromic

Syndromic because of apparent causative mutations in focal epilepsy and Pitt-Hopkins syndrome. Multiple lines of evidence point to CNTNAP2 in autism, including common SNP association to autism diagnosis (Arking et al., 2008; PMID: 18179894 and Anney et al, 2012; PMID: 22843504), a modest increase in the burden of rare variants identified by re-sequencing in individuals with autism (Bakkaloglu et al., 2008; PMID: 18179895), and common SNP association with quantitative language phenotype in individuals with autism (Alarcon et al., 2008; PMID: 18179893). Imaging evidence indicates that the language-associated SNP alters functional connectivity in the cerebral cortex (Vernes et al., 2008; PMID: 18987363; Scott-Van Zeeland et al., 2010; PMID: 21048216). Functional analysis of several CNTNAP2 missense variants originally identified in ASD cases in Bakkaloglu et al., 2008 demonstrated impaired axonal outgrowth in cortical neurons (Canali et al., 2018).

Score Delta: Score remained at 2S

criteria met

See SFARI Gene'scoring criteria

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.

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2021

Score remained at 2S

Description

Reports Added

[Common variants of the autism-associated CNTNAP2 gene contribute to the modulatory effect of social function mediated by temporal cortex2021] [CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case-control study combined with a meta-analysis2021]

1/1/2021

Score remained at 2S

Description

Reports Added

[Comprehensive Genetic Analysis of Non-syndromic Autism Spectrum Disorder in Clinical Settings2021]

7/1/2020

Score remained at 2S

Description

Reports Added

[Genome-wide detection of tandem DNA repeats that are expanded in autism2020]

10/1/2019

Score remained at 2S

New Scoring Scheme

Description

Reports Added

[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]

7/1/2019

Score remained at 2S

Description

Reports Added

[The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children.2019] [Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019]

1/1/2019

Score remained at 2S

Description

Reports Added

[Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders.2018] [Both rare and common genetic variants contribute to autism in the Faroe Islands.2019] [Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS dat...2019] [Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype c...2019]

7/1/2018

Score remained at 2S

Description

Reports Added

[Genetic variants in the CNTNAP2 gene are associated with gender differences among dyslexic children in China.2018]

10/1/2017

Score remained at 2S

Description

Reports Added

[Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.2017]

7/1/2017

Score remained at 2S

Description

Reports Added

[Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration.2017]

4/1/2017

Score remained at 2S

Description

Reports Added

[Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.2008] [A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.2008] [Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.2008] [A functional genetic link between distinct developmental language disorders.2008] [Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder.2009] [Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.2010] [Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case.2010] [CNTNAP2 variants affect early language development in the general population.2011] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Defining the contribution of CNTNAP2 to autism susceptibility.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach.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] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.2013] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.2012] [Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.2006] [Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.2010] [Rare copy number variants are an important cause of epileptic encephalopathies.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome.2014] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.2003] [CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.2007] [A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-relat...2011] [Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K channels.2000] [Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.2008] [Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS.2009] [Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B.2010] [Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.2010] [Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2.2010] [Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.2011] [Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.2012] [CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.2013] [CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.2015] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015] [Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2.2016] [Characterisation of CASPR2 deficiency disorder - a syndrome involving autism, epilepsy and language impairment.2016] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Single nucleotide polymorphisms in the CNTNAP2 gene in Brazilian patients with autistic spectrum disorder.2016] [Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells.2016] [Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and...2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task.2016] [Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.2017]

1/1/2017

Score remained at 2S

Description

Reports Added

[Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task.2016]

10/1/2016

Score remained at 2S

Description

Reports Added

[Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016]

7/1/2016

Score remained at 2S

Description

Reports Added

[Eight further individuals with intellectual disability and epilepsy carrying bi-allelic CNTNAP2 aberrations allow delineation of the mutational and...2016]

4/1/2016

Score remained at 2S

Description

Reports Added

1/1/2016

Score remained at 2S

Description

Reports Added

1/1/2015

Score remained at 2S

Description

Reports Added

[No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contacti...2015]

10/1/2014

Score remained at 2S

Description

Reports Added

[Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach.2014] [A candidate gene association study further corroborates involvement of contactin genes in autism.2014]

7/1/2014

No data

Increased from No data to 2S

Description

Reports Added

[Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K channels.2000] [CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder.2003] [Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2.2006] [CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.2007] [Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.2008] [A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism.2008] [Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.2008] [A functional genetic link between distinct developmental language disorders.2008] [Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons.2008] [Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS.2009] [Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder.2009] [CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in D...2009] [Organization of myelinated axons by Caspr and Caspr2 requires the cytoskeletal adapter protein 4.1B.2010] [Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2.2010] [Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.2010] [Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.2010] [Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2.2010] [Identification of a microdeletion at the 7q33-q35 disrupting the CNTNAP2 gene in a Brazilian stuttering case.2010] [A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-relat...2011] [CNTNAP2 variants affect early language development in the general population.2011] [Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.2011] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1.2011] [Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.2011] [Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental...2011] [Rare copy number variants are an important cause of epileptic encephalopathies.2011] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Individual common variants exert weak effects on the risk for autism spectrum disorderspi.2012] [Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.2012] [Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.2013] [Defining the contribution of CNTNAP2 to autism susceptibility.2013] [Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014] [Diagnostic whole genome sequencing and split-read mapping for nucleotide resolution breakpoint identification in CNTNAP2 deficiency syndrome.2014]

4/1/2014

No data

Increased from No data to 2S

Description

Reports Added

[Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.2014]

Krishnan Probability Score

Score 0.61403089293347

Ranking 134/25841 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 3.8288260734217E-5

Ranking 13588/18225 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 0.95084116029586

Ranking 18649/18665 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 59

Ranking 27/461 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 0.28409542588975

Ranking 2965/20870 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

External PIN Data

BioGRID Human Protein Reference Database

Interaction Table

Interactor Symbol	Interactor Name	Interactor Organism	Interactor Type	Entrez ID	Uniprot ID
ADAM11	Disintegrin and metalloproteinase domain-containing protein 11	Mouse	Protein Binding	11488	Q9R1V4
ADAM22	Disintegrin and metalloproteinase domain-containing protein 22	Mouse	Protein Binding	11496	Q9R1V6
ADAM23	Disintegrin and metalloproteinase domain-containing protein 23	Mouse	Protein Binding	23792	Q9R1V7
CASK	calcium/calmodulin-dependent serine protein kinase (MAGUK family)	Mouse	Protein Binding	12361	O70589
CKMT1	Creatine kinase U-type, mitochondrial	Mouse	Protein Binding	12716	P30275
CNTN2	contactin 2 (axonal)	Human	Protein Binding	6900	Q02246
KCNA1	Potassium voltage-gated channel subfamily A member 1	Mouse	Protein Binding	16485	P16388
KCNA2	potassium voltage-gated channel, shaker-related subfamily, member 2	Mouse	Protein Binding	16490	P63141
KCNA3	Potassium voltage-gated channel subfamily D member 3	Mouse	Protein Binding	56543	Q9Z0V1
KCNA4	potassium voltage-gated channel, shaker-related subfamily, member 4	Mouse	Protein Binding	16492	Q61423
KCNA6	Potassium voltage-gated channel subfamily A member 6	Mouse	Protein Binding	16494	Q61923
KCNAB2	Voltage-gated potassium channel subunit beta-2	Mouse	Protein Binding	16498	P62482
LGI2	leucine-rich repeat LGI family, member 2	Mouse	Protein Binding	246316	Q8K4Z0
LGI3	Leucine-rich repeat LGI family member 3	Mouse	Protein Binding	213469	Q8K406
LGI4	Leucine-rich repeat LGI family member 4	Mouse	Protein Binding	243914	Q8K1S1
Mpdz	multiple PDZ domain protein	Rat	Protein Binding	29365	O55164
PDIA3	protein disulfide isomerase family A, member 3	Human	Protein Binding	2923	P30101
STOX1	storkhead box 1	Human	DNA Binding	219736	Q6ZVD7
TPI1	Triosephosphate isomerase	Mouse	Protein Binding	21991	P17751

Human Gene Module / Chromosome 7 / CNTNAP2

CNTNAP2contactin associated protein-like 2

SFARI Gene Score

Autism Reports / Total Reports

Rare Variants / Common Variants

Aliases

Associated Syndromes

Chromosome Band

Associated Disorders

Relevance to Autism

Molecular Function

External Links

Human

Mouse

Rat

Fruit fly

Zebrafish

SFARI Genomic Platforms

Reports related to CNTNAP2 (101 Reports)

Rare Variants (133)

Common Variants (36)

SFARI Gene score

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

criteria met

Strong Candidate

Syndromic

4/1/2021

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1/1/2021

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7/1/2020

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10/1/2019

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New Scoring Scheme

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4/1/2017

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10/1/2016

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