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Predicting Functional Effects of Missense Variants in Voltage-Gated Sodium and Calcium Channels

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Outgoing claims: the papers this work cites, builds on, or argues with.

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SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome
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De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
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Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia
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Opposing Effects on Na V 1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures
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CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism
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SCN9A Mutations in Paroxysmal Extreme Pain Disorder: Allelic Variants Underlie Distinct Channel Defects and Phenotypes
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Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders
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Progress in Understanding and Treating SCN2A-Mediated Disorders
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Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4
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Absence Epilepsy in Tottering Mutant Mice Is Associated with Calcium Channel Defects
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Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial
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Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine
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Calcium channel characteristics conferred on the sodium channel by single mutations
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An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness
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Targeted gene sequencing in 6994 individuals with neurodevelopmental disorder with epilepsy
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Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies
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Multi-ethnic genome-wide association study for atrial fibrillation
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De novo variants in neurodevelopmental disorders with epilepsy
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Predicting changes to INa from missense mutations in human SCN5A
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A rare schizophrenia risk variant of CACNA1I disrupts CaV3.3 channel activity
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Nonfunctional Na V 1.1 familial hemiplegic migraine mutant transformed into gain of function by partial rescue of folding defects
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Functional heterogeneity of the four voltage sensors of a human L-type calcium channel
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Dynamic action potential clamp predicts functional separation in mild familial and severe de novo forms of SCN2A epilepsy
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Molecular Analysis of the Putative Inactivation Particle in the Inactivation Gate of Brain Type IIA Na+ Channels
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Tracking Voltage-dependent Conformational Changes in Skeletal Muscle Sodium Channel during Activation
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The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials
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De Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of Infancy
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Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders
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UniProt: the Universal Protein knowledgebase
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ClinVar: public archive of interpretations of clinically relevant variants
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The Human Phenotype Ontology in 2017
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UniProt: the universal protein knowledgebase
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A codon-based model of nucleotide substitution for protein-coding DNA sequences.
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Regional missense constraint improves variant deleteriousness prediction
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Gene family information facilitates variant interpretation and identification of disease-associated genes
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ASD and ADHD have a similar burden of rare protein-truncating variants
inferredcites →https://doi.org/10.1101/531210openalex-snapshot
The mutational constraint spectrum quantified from variation in 141,456 humans
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NaV1.1 channels and epilepsy
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Structural Basis for Pharmacology of Voltage-Gated Sodium and Calcium Channels
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Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies
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Genotype phenotype associations across the voltage-gated sodium channel family
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STRUCTURE AND FUNCTION OF VOLTAGE-GATED ION CHANNELS
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SCN5A (Na V 1.5) Variant Functional Perturbation and Clinical Presentation
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Exome Sequencing and Systems Biology Converge to Identify Novel Mutations in the L-Type Calcium Channel, CACNA1C , Linked to Autosomal Dominant Long QT Syndrome
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Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance
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Electrophysiological Properties of Mutant Na v 1.7 Sodium Channels in a Painful Inherited Neuropathy
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Estimating Diversifying Selection and Functional Constraint in the Presence of Recombination
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Biophysics, pathophysiology, and pharmacology of ion channel gating pores

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

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Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders
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SETBP1 variants outside the degron disrupt DNA-binding and transcription independent of protein abundance to cause a heterogeneous neurodevelopmental disorder
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Successful treatment of adult Dravet syndrome patients with cenobamate
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Cenobamate as add‐on treatment for SCN8A developmental and epileptic encephalopathy
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The suitability of high throughput automated patch clamp for physiological applications
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