ArticleMolecular psychiatry2015
Variants of the CNTNAP2 5' promoter as risk factors for autism spectrum disorders: a genetic and functional approach.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 3 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Convergent blood-brain barrier breakdown in schizophrenia and autism spectrum disorders: a systematic review of preclinical animal models.Fluids and barriers of the CNS · 2026Pooled it
- Pooled it
- CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.Journal of neural transmission (Vienna, Austria : 1996) · 2016Pooled it
- The Tumor-suppressive role of CNTNAP2 in glioma: Dual regulation of the NDN-ERK axis and M2 macrophage polarization.Cancer gene therapy · 2026Article
- Newborn metabolomics linking prenatal air pollution exposure and autism spectrum disorder risk in children.Journal of exposure science & environmental epidemiology · 2026Article
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- Genomic and ancestral variations linked to the development of post-acute sequelae of SARS-CoV-2 infection in Indian populations.Frontiers in genetics · 2025Article
- Dysregulated metabolic pathways associated with air pollution exposure and the risk of autism: Evidence from epidemiological studies.Environmental pollution (Barking, Essex : 1987) · 2024Review
- nlr-1/CNTNAP regulates dopamine circuit structure and foraging behaviors in C. elegans.Communications biology · 2024Article
- Decoding the genetic landscape of autism: A comprehensive review.World journal of clinical pediatrics · 2024Article
- Low Plasma Levels of Contactin-Associated Protein-Like 2 in Children with Autism Spectrum Disorder: Links to Neural Development.Neuropsychiatric disease and treatment · 2024Article
- Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1.Bioscience reports · 2023Article
- Evidence for parent-of-origin effects in autism spectrum disorder: a narrative review.Journal of applied genetics · 2023Review
- Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation.Frontiers in molecular neuroscience · 2023Article
- Altered Blood Brain Barrier Permeability and Oxidative Stress inJournal of clinical medicine · 2022Article
- Krüppel-like Transcription Factor 7 Is a Causal Gene in Autism Development.International journal of molecular sciences · 2022Article
- The role of contactin-associated protein-like 2 in neurodevelopmental disease and human cerebral cortex evolution.Frontiers in molecular neuroscience · 2022Review
- Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample.Journal of molecular neuroscience : MN · 2020Article
- High-resolution chromosomal microarray analysis for copy-number variations in high-functioning autism reveals large aberration typical for intellectual disability.Journal of neural transmission (Vienna, Austria : 1996) · 2020Article
- Intronic Variant inFrontiers in pediatrics · 2020Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin gene superfamily, is one of the best-replicated risk genes for autism spectrum disorders (ASD). ASD are predominately genetically determined neurodevelopmental disorders characterized by impairments of language development, social interaction and communication, as well as stereotyped behavior and interests. Although CNTNAP2 expression levels were proposed to alter ASD risk, no study to date has focused on its 5' promoter. Here, we directly sequenced the CNTNAP2 5' promoter region of 236 German families with one child with ASD and detected four novel variants. Furthermore, we genotyped the three most frequent variants (rs150447075, rs34712024, rs71781329) in an additional sample of 356 families and found nominal association of rs34712024G with ASD and rs71781329GCG[7] with language development. The four novel and the three known minor alleles of the identified variants were predicted to alter transcription factor binding sites (TFBS). At the functional level, the respective sequences spanning these seven variants were bound by nuclear factors. In a luciferase promoter assay, the respective minor alleles showed cell line-specific and differentiation stage-dependent effects at the level of promoter activation. The novel potential rare risk-variant M2, a G>A mutation -215 base pairs 5' of the transcriptional start site, significantly reduced promoter efficiency in HEK293T and in undifferentiated and differentiated neuroblastoid SH-SY5Y cells. This variant was transmitted to a patient with autistic disorder. The under-transmitted, protective minor G allele of the common variant rs34712024, in contrast, increased transcriptional activity. These results lead to the conclusion that the pathomechanism of CNTNAP2 promoter variants on ASD risk is mediated by their effect on TFBSs, and thus confirm the hypothesis that a reduced CNTNAP2 level during neuronal development increases liability for ASD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.