ArticleAmerican journal of human genetics2015
A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Genetic assessment of consecutively recruited dystonia cases from a single center.Neurogenetics · 2026Article
- How Early Should I Refer My Patient? The Benefits of a Quick Ophthalmic Referral in Spinocerebellar Ataxias, a Case Series and Literature Review.Brain sciences · 2026Article
- The four voltage-sensing domains of T-type calcium channels activate near the resting membrane potential.Nature communications · 2026Article
- From early psychiatric symptoms to an adolescent diagnosis: Clues from childhood in spinocerebellar ataxia Type-42.Dusunen adam : Bakirkoy Ruh ve Sinir Hastaliklari Hastanesi yayin organi · 2026Article
- Two pairs of CACNA1I (CaV3.3) variants with opposite effects on channel function cause neurodevelopmental disorders of varying severity.PLoS genetics · 2025Article
- Living on the Rocks: Genomic Analysis of Limestone Langurs Provides Novel Insights into the Adaptive Evolution in Extreme Karst Environments.Genomics, proteomics & bioinformatics · 2025Article
- CACNA1G, A Heterotaxy Candidate Gene, Plays a Role in Ciliogenesis and Left-Right Patterning in Xenopus tropicalis.Genesis (New York, N.Y. : 2000) · 2025Article
- Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome.Scientific reports · 2025Article
- Electrophysiological classification ofFrontiers in pharmacology · 2025Article
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- CACNA1G Causes Dominantly Inherited Myoclonus-Ataxia with Intellectual Disability: A Case Report.Cerebellum (London, England) · 2024Article
- Channelopathies in epilepsy: an overview of clinical presentations, pathogenic mechanisms, and therapeutic insights.Journal of neurology · 2024Review
- The T-type calcium channelosome.Pflugers Archiv : European journal of physiology · 2024Review
- Dysregulation of alternative splicing in spinocerebellar ataxia type 1.Human molecular genetics · 2024Article
- Tremor in Spinocerebellar Ataxia: A Scoping Review.Tremor and other hyperkinetic movements (New York, N.Y.) · 2024Article
- Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.International journal of molecular sciences · 2023Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- Rapidly Progressive Atypical Parkinsonism as a Presenting Feature of ATX-Movement disorders clinical practice · 2023Article
- T-type calcium channels as therapeutic targets in essential tremor and Parkinson's disease.Annals of clinical and translational neurology · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs.
Indexed as
Identifiers
What OpenQuestion holds
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.