Developmental Brain Disorder Gene Database

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Missense

SCN8A

HGNC:10596 (protein-coding gene)

sodium voltage-gated channel alpha subunit 8

Unique Cases:
62
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
January 4, 2024

Summary
Cases
Publications
External

Gene Summary:

Gene Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes (PubMed:29726066). Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. {ECO:0000269|PubMed:19136557, ECO:0000269|PubMed:29726066, ECO:0000269|PubMed:33245860, ECO:0000269|PubMed:36696443, ECO:0000269|PubMed:36823201}. [Isoform 5]: In macrophages... (Source: Uniprot)
Previous symbols
MED
Alias symbols
Nav1.6, NaCh6, PN4, CerIII, CIAT
Chromosomal Location
12q13.13
Genomic Coordinates
GRCh37:chr12:51985020-52206648
GRCh38:chr12:51591233-51812864
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

5.53

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.13

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive4 Supportive3 Strong4 Limited1

Publications:

Rochtus A et. al., Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort., Epilepsia, 2020
Na JH et. al., Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy., Brain Dev, 2020
Fatema K et. al., SCN8A Mutation in Infantile Epileptic Encephalopathy: Report of Two Cases., J Epilepsy Res, 2019
Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020
Ostrander BEP et. al., Whole-genome analysis for effective clinical diagnosis and gene discovery in early infantile epileptic encephalopathy., NPJ Genom Med, 2018
Møller RS et. al., Parental mosaicism in epilepsies due to alleged de novo variants., Epilepsia, 2019
Costain G et. al., Clinical Application of Targeted Next-Generation Sequencing Panels and Whole Exome Sequencing in Childhood Epilepsy., Neuroscience, 2019
Snoeijen-Schouwenaars FM et. al., Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability., Epilepsia, 2019
Fung CW et. al., Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic encephalopathy., Epilepsia Open, 2017
Wang J et. al., Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome., Seizure, 2019
Demos M et. al., Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy., Front Neurol, 2019
Xie H et. al., De novo SCN1A, SCN8A, and CLCN2 mutations in childhood absence epilepsy., Epilepsy Res, 2019
Papuc SM et. al., The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study., Eur J Hum Genet, 2019
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Jang SS et. al., Diagnostic Yield of Epilepsy Panel Testing in Patients With Seizure Onset Within the First Year of Life., Front Neurol, 2019
Kothur K et. al., Diagnostic yield of targeted massively parallel sequencing in children with epileptic encephalopathy., Seizure, 2018
Epilepsy Genetics Initiative. et. al., The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield., Epilepsia, 2019
Peng J et. al., Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy., CNS Neurosci Ther, 2019
Yang L et. al., Clinical and genetic spectrum of a large cohort of children with epilepsy in China., Genet Med, 2019
Yuskaitis CJ et. al., Infantile Spasms of Unknown Cause: Predictors of Outcome and Genotype-Phenotype Correlation., Pediatr Neurol, 2018
Fernández-Marmiesse A et. al., Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients., Front Neurosci, 2019
Chérot E et. al., Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients., Clin Genet, 2018
Ko A et. al., Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy., Epilepsy Res, 2018
Balciuniene J et. al., Use of a Dynamic Genetic Testing Approach for Childhood-Onset Epilepsy., JAMA Netw Open, 2019
Arafat A et. al., Unexplained Early Infantile Epileptic Encephalopathy in Han Chinese Children: Next-Generation Sequencing and Phenotype Enriching., Sci Rep, 2017
Takata A et. al., Comprehensive analysis of coding variants highlights genetic complexity in developmental and epileptic encephalopathy., Nat Commun, 2019
Lin KM et. al., A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report., BMC Pediatr, 2019
Salinas V et. al., Clinical next generation sequencing in developmental and epileptic encephalopathies: Diagnostic relevance of data re-analysis and variants re-interpretation., Eur J Med Genet, 2021
van Eyk CL et. al., Targeted resequencing identifies genes with recurrent variation in cerebral palsy., NPJ Genom Med, 2019
McMichael G et. al., Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy., Mol Psychiatry, 2015
Lee HF et. al., Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders., Dev Med Child Neurol, 2021
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
Varesio C et. al., Diagnostic Yield and Cost-Effectiveness of "Dynamic" Exome Analysis in Epilepsy with Neurodevelopmental Disorders: A Tertiary-Center Experience in Northern Italy., Diagnostics (Basel), 2021
Sun D et. al., Detection of Disease-Causing SNVs/Indels and CNVs in Single Test Based on Whole Exome Sequencing: A Retrospective Case Study in Epileptic Encephalopathies., Front Pediatr, 2021

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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