ArticlePLoS genetics2019
An autism-causing calcium channel variant functions with selective autophagy to alter axon targeting and behavior.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Prenatal cell-free DNA methylome detects association with autism and maternal obesity.Communications biology · 2026Article
- Connectivity of the adult human brain with sequential neurogenesis of circuits and transcriptomics signatures.Nature communications · 2025Article
- Axon termination of the SAB motor neurons inbioRxiv : the preprint server for biology · 2025Article
- Impaired macroautophagy confers substantial risk for intellectual disability in children with autism spectrum disorders.Molecular psychiatry · 2025Article
- Article
- Autism candidate genebioRxiv : the preprint server for biology · 2024Article
- Molecular regulation of axon termination in mechanosensory neurons.Development (Cambridge, England) · 2024Review
- Article
- UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.bioRxiv : the preprint server for biology · 2024Article
- Genetic etiology of autism spectrum disorder in the African population: a scoping review.Frontiers in genetics · 2024Article
- UNC-116 and UNC-16 function with the NEKL-3 kinase to promote axon targeting.Development (Cambridge, England) · 2023Article
- Current updates on arrhythmia within Timothy syndrome: genetics, mechanisms and therapeutics.Expert reviews in molecular medicine · 2023Review
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Orexin/Hypocretin System Dysfunction in ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations).Neuropsychiatric disease and treatment · 2022Article
- A null allele in themicroPublication biology · 2022Article
- Autophagy in axonal and presynaptic development.Current opinion in neurobiology · 2021Review
- An autism-associated calcium channel variant causes defects in neuronal polarity in the ALM neuron ofmicroPublication biology · 2021Article
- Update on the Molecular Genetics of Timothy Syndrome.Frontiers in pediatrics · 2021Review
- Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour.PloS one · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Common and rare variants of the CACNA1C voltage-gated calcium channel gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD. However, little is known about how CACNA1C variants affect cellular processes to alter neurodevelopment. The Timothy syndrome mutation is a rare de novo gain-of-function variant in CACNA1C that causes autism with high penetrance, providing a powerful avenue into investigating the role of CACNA1C variants in neurodevelopmental disorders. Here, we use egl-19, the C. elegans homolog of CACNA1C, to investigate the role of voltage-gated calcium channels in autism. We show that an egl-19(gof) mutation that is equivalent to the Timothy syndrome mutation can alter axon targeting and affect behavior in C. elegans. We find that wildtype egl-19 negatively regulates axon termination. The egl-19(gof) mutation represses axon termination to cause axon targeting defects that lead to the misplacement of electrical synapses and alterations in habituation to light touch. Moreover, genetic interactions indicate that the egl-19(gof) mutation functions with genes that promote selective autophagy to cause defects in axon termination and behavior. These results reveal a novel genetic mechanism whereby a de novo mutation in CACNA1C can drive alterations in circuit formation and behavior.
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Registered trials
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.