SCN8A
Homo sapiens
Gene Name: sodium channel, voltage gated, type VIII, alpha subunit
Aliases: CERIII, CIAT, MED, NaCh6, Nav1.6, PN4
Chromosome No: 12
Chromosome Band: 12q13.13
Genetic Category: Rare single gene variant-Syndromic--Functional-Rare single gene variant/Functional
Aliases: CERIII, CIAT, MED, NaCh6, Nav1.6, PN4
Chromosome No: 12
Chromosome Band: 12q13.13
Genetic Category: Rare single gene variant-Syndromic--Functional-Rare single gene variant/Functional
Summary Statistics:
ASD Reports: 61
Recent Reports: 2
Annotated variants: 226
Associated CNVs: 1
Evidence score: 4
ASD Reports: 61
Recent Reports: 2
Annotated variants: 226
Associated CNVs: 1
Evidence score: 4
| Associated Disorders: |
|
Relevance to Autism
A rare de novo mutation in the SCN8A gene was found in a patient with epilepsy, autism, intellectual disability and developmental delay (Veeramah et al., 2012).
Molecular Function
This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with mental retardation, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP.
Epilepsy
Autism
Positive Association
De novo mutations in epileptic encephalopathies.
Epilepsy
IS, LGS, DD, ID, ASD, ADHD
Support
Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.
Epilepsy/seizures
Support
Social Deficits and Cerebellar Degeneration in Purkinje Cell Scn8a Knockout Mice
ASD
Support
A multi-disciplinary clinic for SCN8A-related epilepsy.
Epilepsy/seizures
ASD
Support
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.
ASD, DD
Support
The phenotypic spectrum of SCN8A encephalopathy.
Early infantile epileptic encephalopathy-13 (EIEE1
Support
Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications
DD, ID, epilepsy/seizures
Support
The phenotype of SCN8A developmental and epileptic encephalopathy.
Early infantile epileptic encephalopathy-13 (EIEE1
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
ID
Support
Genetic analysis using targeted exome sequencing of 53 Vietnamese children with developmental and epileptic encephalopathies
DD, epilepsy/seizures
Support
A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report.
Early infantile epileptic encephalopathy-13 (EIEE1
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ASD, ID, epilepsy/seizures
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Epilepsy/seizures
ID, microcephaly
Support
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study
DD, epilepsy/seizures
Support
De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy.
Epileptic encephalopathy
DD, epilepsy/seizures
Support
Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy.
Epilepsy/seizures, ID
Support
Commonalities and distinctions between two neurodevelopmental disorder subtypes associated with SCN2A and SCN8A variants and literature review
DD, ID
Support
Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.
ASD
Support
A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.
Epilepsy/seizures
Support
Monogenic developmental and epileptic encephalopathies of infancy and childhood
DD, ID, epilepsy/seizures
Support
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Epilepsy
ID, ASD, DD
Support
Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort
Epilepsy/seizures
ASD, DD
Support
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.
Epilepsy/seizures
DD/ID
Support
Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?
Epilepsy/seizures
Developmental regression, progressive cerebellar a
Support
Rare variants in the outcome of social skills group training for autism
ASD
Support
Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.
ASD
Epilepsy/seizures
Support
Novel SCN8A mutation in a girl with refractory seizures and autistic features.
Epilepsy/seizures, autistic features
Support
Impaired Neurodevelopmental Genes in Slovenian Autistic Children Elucidate the Comorbidity of Autism With Other Developmental Disorders
DD
Autistic behavior
Support
Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.
ID
Epilepsy, ASD
Support
Genome sequencing broadens the range of contributing variants with clinical implications in schizophrenia
SCZ
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Support
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
DD, ID, epilepsy/seizures
Support
Autism spectrum disorder and comorbid neurodevelopmental disorders (ASD-NDDs): Clinical and genetic profile of a pediatric cohort
ASD
Epilepsy/seizures
Support
The spectrum of intermediate SCN8A-related epilepsy.
Epilepsy/seizures
ID, ASD or autistic features
Support
SCN8A mutation in a child presenting with seizures and developmental delays.
Epilepsy/seizures, DD, ID
Support
Clinical Targeted Panel Sequencing Analysis in Clinical Evaluation of Children with Autism Spectrum Disorder in China
ASD
Support
Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.
Epilepsy
Support
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
ASD, DD
Support
Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.
ID, epilepsy/seizures
Microcephaly
Support
Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.
Lennox-Gastaut syndrome
Epilepsy
Support
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
ASD
Support
The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.
Epilepsy/seizures
Support
De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis.
Epilepsy/seizures, DD
ASD, ID
Support
Genetic and Phenotype Analysis of a Chinese Cohort of Infants and Children With Epilepsy
Epilepsy/seizures
Support
Overrepresentation of genetic variation in the AnkyrinG interactome is related to a range of neurodevelopmental disorders
Epilepsy/seizures
DD, ID, psychomotor retardation
Support
Loss-of-function variants of SCN8A in intellectual disability without seizures.
DD, ID
ADHD, social communication disorder
Support
De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.
DD, ID
Epilepsy/seizures, ASD
Support
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
DD, ID
Support
Neuronal mechanisms of mutations in SCN8A causing epilepsy or intellectual disability.
ASD, ID, epilepsy/seizures
Recent Recommendation
Regulation of Thalamic and Cortical Network Synchrony by Scn8a.
Recent Recommendation
Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy.
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN327R014
missense_variant
c.4750G>A
p.Gly1584Ser
De novo
Simplex
GEN327R015
missense_variant
c.643A>G
p.Asn215Asp
De novo
Simplex
GEN327R034
missense_variant
c.5630A>G
p.Asn1877Ser
Familial
Paternal
Multi-generational
GEN327R047
missense_variant
c.5630A>G
p.Asn1877Ser
Familial
Maternal
Multi-generational
GEN327R108
missense_variant
c.411C>G
p.Ile137Met
Familial
Maternal
Multi-generational
GEN327R109
missense_variant
c.1122C>G
p.Asn374Lys
De novo
Extended multiplex
GEN327R110
frameshift_variant
c.1630_1631del
p.Asn544SerfsTer38
Familial
Maternal
Multi-generational
GEN327R111
missense_variant
c.2287A>G
p.Ile763Val
De novo
Extended multiplex
GEN327R113
missense_variant
c.2671G>A
p.Val891Met
Familial
Maternal
Multi-generational
GEN327R114
missense_variant
c.2806G>A
p.Glu936Lys
Unknown
Not maternal
Multi-generational
GEN327R120
missense_variant
c.4391T>C
p.Ile1464Thr
Familial
Paternal
Multi-generational
GEN327R139
missense_variant
c.5615G>A
p.Arg1872Gln
Familial
Paternal
Multi-generational
GEN327R141
missense_variant
c.5630A>G
p.Asn1877Ser
Familial
Paternal
Multi-generational
GEN327R163
missense_variant
c.5710C>T
p.Arg1904Cys
Familial
Paternal
Simplex
GEN327R184
frameshift_variant
c.1940_1957delins
p.Gly647ValfsTer18
Unknown
Simplex
GEN327R189
frameshift_variant
c.3941del
p.Tyr1314SerfsTer38
De novo
Simplex
GEN327R213
missense_variant
c.4499C>T
p.Pro1500Leu
Familial
Maternal
Extended multiplex
Common
No Common Variants Available
