ArticleAnnals of neurology2012
Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- Genetic associations for keratoconus: a systematic review and meta-analysis.Scientific reports · 2017Pooled it
- Insights from cerebellar transcriptomic analysis into the pathogenesis of ataxia.JAMA neurology · 2014Trial
- Genotype and Age at Onset Drive Vermis Atrophy in CACNA1A- and GAA-FGF14-related Ataxias.Cerebellum (London, England) · 2026Article
- Ventricular ion channels and arrhythmias: an overview of physiology, pathophysiology and pharmacology.Medical review (2021) · 2025Review
- Restoration of Shal/KCellular and molecular life sciences : CMLS · 2025Article
- Functional characterization of two KCND3 variants associated with SCA 19/22 ataxia in Latin American families.Biological research · 2025Article
- A dominant negative Kcnd3 F227del mutation in mice causes spinocerebellar ataxia type 22 (SCA22) by impairing ER and Golgi functioning.The Journal of pathology · 2025Article
- A novel KCND3 variant in the N-terminus impairs the ionic current of Kv4.3 and is associated with SCA19/22.Journal of cellular and molecular medicine · 2024Article
- Potential Benefit of Channel Activators in Loss-of-Function Primary Potassium Channelopathies Causing Heredoataxia.Cerebellum (London, England) · 2024Review
- Oxidative stress and ion channels in neurodegenerative diseases.Frontiers in physiology · 2024Review
- Therapeutic role of voltage-gated potassium channels in age-related neurodegenerative diseases.Frontiers in cellular neuroscience · 2024Review
- Molecular Mimicry between Meningococcal B Factor H-Binding Protein and Human Proteins.Global medical genetics · 2023Article
- An E280K Missense Variant inInternational 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
- Pediatric-Onset Epilepsy and Developmental Epileptic Encephalopathies Followed by Early-Onset Parkinsonism.International journal of molecular sciences · 2023Review
- Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss.Frontiers in molecular neuroscience · 2023Review
- A Second Case With the V374ANeurology. Genetics · 2022Article
- The Regulation of MiTF/TFE Transcription Factors Across Model Organisms: from Brain Physiology to Implication for Neurodegeneration.Molecular neurobiology · 2022Review
- Feasibility of Follow-Up Studies and Reclassification in Spinocerebellar Ataxia Gene Variants of Unknown Significance.Frontiers in genetics · 2022Article
- Rare KCND3 Loss-of-Function Mutation Associated With the SCA19/22.Frontiers in molecular neuroscience · 2022Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo identify the causative gene for the neurodegenerative disorder spinocerebellar ataxia type 19 (SCA19) located on chromosomal region 1p21-q21.
methodsExome sequencing was used to identify the causal mutation in a large SCA19 family. We then screened 230 ataxia families for mutations located in the same gene (KCND3, also known as Kv4.3) using high-resolution melting. SCA19 brain autopsy material was evaluated, and in vitro experiments using ectopic expression of wild-type and mutant Kv4.3 were used to study protein localization, stability, and channel activity by patch-clamping.
resultsWe detected a T352P mutation in the third extracellular loop of the voltage-gated potassium channel KCND3 that cosegregated with the disease phenotype in our original family. We identified 2 more novel missense mutations in the channel pore (M373I) and the S6 transmembrane domain (S390N) in 2 other ataxia families. T352P cerebellar autopsy material showed severe Purkinje cell degeneration, with abnormal intracellular accumulation and reduced protein levels of Kv4.3 in their soma. Ectopic expression of all mutant proteins in HeLa cells revealed retention in the endoplasmic reticulum and enhanced protein instability, in contrast to wild-type Kv4.3 that was localized on the plasma membrane. The regulatory β subunit Kv channel interacting protein 2 was able to rescue the membrane localization and the stability of 2 of the 3 mutant Kv4.3 complexes. However, this either did not restore the channel function of the membrane-located mutant Kv4.3 complexes or restored it only partially.
interpretationKCND3 mutations cause SCA19 by impaired protein maturation and/or reduced channel function.
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.