Summary Statistics:
Gene Score: 3
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.
References
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
A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report.
Early infantile epileptic encephalopathy-13 (EIEE1
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
DD, epilepsy/seizures
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ASD, ID, epilepsy/seizures
Support
Integrating de novo and inherited variants in 42
ASD
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
Epilepsy/seizures
DD
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
The Genetic Puzzle of Cerebral Palsy: Results of a Monocentric Study
Cerebral palsy
DD, epilepsy/seizures
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
ASD, DD, ID, epilepsy/seizures
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
Genetic Diagnostic Yield in Autism Spectrum Disorder (ASD) and Epilepsy Phenotypes in Children with Genetically Defined ASD
ASD
ADHD, ID, 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
Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
DD
ID
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
Genetic diagnostic outcomes from a 10-year research programme in autism in Aotearoa New Zealand
ASD
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
Molecular and cellular context influences SCN8A variant function
DD, epilepsy/seizures
ASD, ID
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
Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses
ASD, DD, ID, epilepsy/seizures
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
Support
Expanding the genotype-phenotype spectrum in SCN8A-related disorders
Epilepsy/seizures
ASD, ADHD, DD, ID
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
Trio-whole exome sequencing reveals the importance of de novo variants in children with intellectual disability and developmental delay
DD, epilepsy/seizures
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
Neurodevelopmental outcomes in a cohort of Australian families with self-limited familial epilepsy of neonatal/infantile onset
Epilepsy/seizures
DD, autistic features
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
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.
GEN327R001
missense_variant
c.5302A>G
p.Asn1768Asp
De novo
GEN327R002
synonymous_variant
c.5601G>A
p.Gln1867=
Unknown
Unknown
GEN327R003
missense_variant
c.1915C>T
p.Arg639Cys
Unknown
Unknown
GEN327R004
missense_variant
c.3076C>T
p.Arg1026Cys
Unknown
Unknown
GEN327R005
missense_variant
c.3818C>T
p.Ala1273Val
Unknown
Unknown
GEN327R006
missense_variant
c.5215C>T
p.Pro1739Ser
Unknown
Unknown
GEN327R007
intron_variant
NM_014191:C>G
Unknown
Unknown
GEN327R008
missense_variant
c.4850G>A
p.Arg1617Gln
De novo
Simplex
GEN327R009
missense_variant
c.3868C>G
p.Leu1290Val
Familial
Paternal
GEN327R010
missense_variant
c.1984C>T
p.Arg662Cys
Unknown
GEN327R011
missense_variant
c.5492G>A
p.Arg1831Gln
Unknown
GEN327R012
missense_variant
c.641G>A
p.Gly214Asp
De novo
GEN327R013
missense_variant
c.2624T>A
p.Leu875Gln
De novo
GEN327R014
missense_variant
c.4750G>A
p.Gly1584Ser
De novo
Simplex
GEN327R015
missense_variant
c.643A>G
p.Asn215Asp
De novo
Simplex
GEN327R016
missense_variant
c.2952C>G
p.Asn984Lys
De novo
GEN327R017
missense_variant
c.4351G>A
p.Gly1451Ser
De novo
GEN327R018
missense_variant
c.172G>A
p.Asp58Asn
De novo
GEN327R019
missense_variant
c.2668G>A
p.Ala890Thr
De novo
GEN327R020
missense_variant
c.4727G>A
p.Arg1576Gln
De novo
GEN327R021
missense_variant
c.1221G>C
p.Leu407Phe
De novo
GEN327R022
missense_variant
c.2549G>A
p.Arg850Gln
De novo
GEN327R023
missense_variant
c.4787C>G
p.Ser1596Cys
De novo
GEN327R024
missense_variant
c.4935G>A
p.Met1645Ile
De novo
GEN327R025
missense_variant
c.5492G>A
p.Arg1831Gln
De novo
GEN327R026
missense_variant
c.1588C>T
p.Arg530Trp
Familial
Paternal
GEN327R027
missense_variant
c.5615G>T
p.Arg1872Leu
De novo
GEN327R028
missense_variant
c.5615G>T
p.Arg1872Leu
De novo
GEN327R029
missense_variant
c.5615G>A
p.Arg1872Gln
De novo
GEN327R030
missense_variant
c.641G>A
p.Gly214Asp
De novo
GEN327R031
missense_variant
c.2287A>G
p.Ile763Val
De novo
Multiplex
GEN327R032
missense_variant
c.3985A>G
p.Asn1329Asp
De novo
Simplex
GEN327R033
missense_variant
c.3995T>G
p.Leu1332Arg
De novo
Simplex
GEN327R034
missense_variant
c.5630A>G
p.Asn1877Ser
Familial
Paternal
Multi-generational
GEN327R035
missense_variant
c.302A>G
p.Lys101Arg
Familial
Maternal
Simplex
GEN327R036
missense_variant
c.202A>G
p.Ile68Val
Unknown
GEN327R037
missense_variant
c.2098A>T
p.Ile700Leu
Unknown
GEN327R038
missense_variant
c.2415A>G
p.Ile805Met
Unknown
GEN327R039
missense_variant
c.3076C>T
p.Arg1026Cys
Unknown
GEN327R040
missense_variant
c.3097C>G
p.Pro1033Ala
Unknown
GEN327R041
missense_variant
c.3148G>A
p.Gly1050Ser
Unknown
GEN327R042
missense_variant
c.5879G>A
p.Arg1960Gln
Unknown
GEN327R043
missense_variant
c.800T>C
p.Leu267Ser
De novo
Simplex
GEN327R044
missense_variant
c.4423G>A
p.Gly1475Arg
De novo
GEN327R045
missense_variant
c.4948G>A
p.Ala1650Thr
De novo
GEN327R046
missense_variant
c.5491C>T
p.Arg1831Trp
De novo
GEN327R047
missense_variant
c.5630A>G
p.Asn1877Ser
Familial
Maternal
Multi-generational
GEN327R048
missense_variant
c.2932A>G
p.Ser978Gly
De novo
GEN327R049
missense_variant
c.4214C>A
p.Ala1405Asp
De novo
GEN327R050
missense_variant
c.5615G>A
p.Arg1872Gln
De novo
GEN327R051
missense_variant
c.4727G>A
p.Arg1576Gln
De novo
GEN327R052
missense_variant
c.5276A>G
p.Asn1759Ser
Unknown
GEN327R053
missense_variant
c.4850G>A
p.Arg1617Gln
De novo
GEN327R054
missense_variant
c.644A>G
p.Asn215Ser
Familial
Maternal
GEN327R055
missense_variant
c.4877G>A
p.Arg1626His
Unknown
GEN327R056
missense_variant
c.4394A>T
p.Asp1465Val
De novo
GEN327R057
missense_variant
c.1588C>T
p.Arg530Trp
Familial
Simplex
GEN327R058
missense_variant
c.1920C>A
p.Asn640Lys
Familial
Simplex
GEN327R059
missense_variant
c.2130A>C
p.Glu710Asp
Familial
Simplex
GEN327R060
missense_variant
c.3928G>A
p.Gly1310Arg
Familial
Simplex
GEN327R061
missense_variant
c.4051G>A
p.Gly1351Arg
Familial
Simplex
GEN327R062
missense_variant
c.2890G>C
p.Gly964Arg
De novo
GEN327R063
missense_variant
c.3652G>A
p.Glu1218Lys
Unknown
Not maternal
GEN327R064
missense_variant
c.667A>G
p.Arg223Gly
De novo
GEN327R065
missense_variant
c.632T>C
p.Val211Ala
De novo
GEN327R066
missense_variant
c.692T>C
p.Ile231Thr
De novo
GEN327R067
splice_site_variant
c.4174A>G
p.Lys1392Glu
De novo
Simplex
GEN327R068
missense_variant
c.3844G>A
p.Ala1282Thr
De novo
Simplex
GEN327R069
missense_variant
c.5507A>G
p.Asn1836Ser
De novo
Simplex
GEN327R070
missense_variant
c.5492G>A
p.Arg1831Gln
De novo
Simplex
GEN327R071
missense_variant
c.4228G>A
p.Ala1410Thr
De novo
Simplex
GEN327R072
missense_variant
c.4850G>A
p.Arg1617Gln
De novo
GEN327R073
missense_variant
c.2879T>A
p.Val960Asp
De novo
GEN327R074
missense_variant
c.5401C>G
p.Gln1801Glu
De novo
GEN327R075
missense_variant
c.5615G>A
p.Arg1872Gln
De novo
GEN327R076
missense_variant
c.2668G>A
p.Ala890Thr
De novo
GEN327R077
missense_variant
c.4435A>G
p.Ile1479Val
De novo
GEN327R078
missense_variant
c.5491C>T
p.Arg1831Trp
De novo
GEN327R079
missense_variant
c.779T>C
p.Phe260Ser
De novo
GEN327R080
missense_variant
c.4814T>G
p.Ile1605Arg
De novo
GEN327R081
missense_variant
NM_001330260.2:c.5524C>T
p.Arg1872Gln
De novo
GEN327R082
missense_variant
c.1228G>T
p.Val410Leu
De novo
GEN327R083
splice_site_variant
c.4296+1del
De novo
GEN327R084
missense_variant
c.4814T>G
p.Ile1605Arg
De novo
GEN327R085
missense_variant
c.706+185_706+186delinsGG
De novo
GEN327R086
missense_variant
c.4774G>C
p.Val1592Leu
De novo
GEN327R087
missense_variant
c.5614C>T
p.Arg1872Trp
De novo
GEN327R088
missense_variant
c.1201T>C
p.Tyr401His
De novo
GEN327R089
missense_variant
c.2549G>T
p.Arg850Leu
De novo
GEN327R090
missense_variant
c.2590C>G
p.Leu864Val
De novo
GEN327R091
missense_variant
c.2932A>G
p.Ser978Gly
De novo
GEN327R092
missense_variant
c.4300G>A
p.Gly1434Arg
De novo
GEN327R093
missense_variant
c.4423G>A
p.Gly1475Arg
De novo
GEN327R094
missense_variant
c.4423G>A
p.Gly1475Arg
De novo
GEN327R095
missense_variant
c.4472C>T
p.Ala1491Val
De novo
GEN327R096
missense_variant
c.4472C>T
p.Ala1491Val
De novo
GEN327R097
missense_variant
c.4493A>T
p.Lys1498Met
De novo
GEN327R098
missense_variant
c.4594A>T
p.Ile1532Phe
De novo
GEN327R099
missense_variant
c.4639T>G
p.Phe1547Val
De novo
GEN327R100
missense_variant
c.5292C>G
p.Ile1764Met
De novo
GEN327R101
missense_variant
c.4859G>T
p.Arg1620Leu
De novo
GEN327R102
missense_variant
c.4865C>A
p.Ala1622Asp
De novo
GEN327R103
missense_variant
c.5614C>T
p.Arg1872Trp
De novo
GEN327R104
missense_variant
c.4423G>A
p.Gly1475Arg
De novo
GEN327R105
missense_variant
c.5280G>A
p.Met1760Ile
De novo
GEN327R106
missense_variant
c.2890G>C
p.Gly964Arg
De novo
GEN327R107
5_prime_UTR_variant
c.-8A>G
De novo
Simplex
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
GEN327R112
missense_variant
c.2287A>G
p.Ile763Val
De novo
Simplex
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
GEN327R115
missense_variant
c.3601G>A
p.Glu1201Lys
De novo
Simplex
GEN327R116
missense_variant
c.3722A>G
p.Tyr1241Cys
Unknown
Simplex
GEN327R117
missense_variant
c.3953A>G
p.Asn1318Ser
De novo
Simplex
GEN327R118
missense_variant
c.3956C>A
p.Ala1319Asp
De novo
Simplex
GEN327R119
missense_variant
c.3967G>A
p.Ala1323Thr
De novo
Simplex
GEN327R120
missense_variant
c.4391T>C
p.Ile1464Thr
Familial
Paternal
Multi-generational
GEN327R121
missense_variant
c.4300G>A
p.Gly1434Arg
Unknown
Multiplex
GEN327R122
missense_variant
c.4423G>A
p.Gly1475Arg
De novo
Simplex
GEN327R123
missense_variant
c.4423G>A
p.Gly1475Arg
De novo
Simplex
GEN327R124
missense_variant
c.4447G>A
p.Glu1483Lys
De novo
Simplex
GEN327R125
missense_variant
c.4585A>G
p.Met1529Val
De novo
Simplex
GEN327R126
missense_variant
c.4764C>G
p.Phe1588Leu
De novo
Simplex
GEN327R127
missense_variant
c.4764C>A
p.Phe1588Leu
De novo
Simplex
GEN327R128
missense_variant
c.4840A>G
p.Thr1614Ala
De novo
Simplex
GEN327R129
missense_variant
c.4850G>C
p.Arg1617Pro
De novo
Simplex
GEN327R130
missense_variant
c.4727G>C
p.Arg1576Pro
De novo
GEN327R131
missense_variant
c.4850G>C
p.Arg1617Pro
De novo
Simplex
GEN327R132
missense_variant
c.4949C>T
p.Ala1650Val
De novo
Simplex
GEN327R133
missense_variant
c.4961T>A
p.Ile1654Asn
Unknown
Simplex
GEN327R134
missense_variant
c.5273T>C
p.Val1758Ala
De novo
Simplex
GEN327R135
missense_variant
c.5311G>A
p.Val1771Ile
De novo
Simplex
GEN327R136
stop_gained
c.5458C>T
p.Arg1820Ter
De novo
Simplex
GEN327R137
missense_variant
c.5497G>C
p.Asp1833His
Unknown
Simplex
GEN327R138
missense_variant
c.5597G>A
p.Arg1866Gln
De novo
Simplex
GEN327R139
missense_variant
c.5615G>A
p.Arg1872Gln
Familial
Paternal
Multi-generational
GEN327R140
missense_variant
c.5507A>G
p.Asn1836Ser
Unknown
Simplex
GEN327R141
missense_variant
c.5630A>G
p.Asn1877Ser
Familial
Paternal
Multi-generational
GEN327R142
missense_variant
c.5630A>G
p.Asn1877Ser
Unknown
Simplex
GEN327R143
missense_variant
c.1207G>A
p.Val403Met
Unknown
Multiplex
GEN327R144
missense_variant
c.5257T>G
p.Ser1753Ala
De novo
GEN327R145
missense_variant
c.752T>C
p.Leu251Pro
De novo
GEN327R146
missense_variant
c.3953A>G
p.Asn1318Ser
De novo
Simplex
GEN327R147
missense_variant
c.769C>G
p.Leu257Val
De novo
GEN327R148
missense_variant
c.1157C>G
p.Thr386Arg
Unknown
GEN327R149
stop_gained
c.1759G>T
p.Glu587Ter
De novo
GEN327R150
missense_variant
c.2549G>A
p.Arg850Gln
De novo
GEN327R151
missense_variant
c.3960G>T
p.Leu1320Phe
Unknown
GEN327R152
missense_variant
c.3988G>A
p.Val1330Met
De novo
GEN327R153
missense_variant
c.4382G>T
p.Gly1461Val
Unknown
GEN327R154
missense_variant
c.4423G>A
p.Gly1475Arg
Unknown
GEN327R155
missense_variant
c.4423G>A
p.Gly1475Arg
De novo
GEN327R156
missense_variant
c.4435A>G
p.Ile1479Val
De novo
GEN327R157
missense_variant
c.4850G>A
p.Arg1617Gln
De novo
GEN327R158
missense_variant
c.4889T>C
p.Leu1630Pro
De novo
GEN327R159
missense_variant
c.5276A>G
p.Asn1759Ser
Unknown
GEN327R160
missense_variant
c.5615G>T
p.Arg1872Leu
De novo
GEN327R161
missense_variant
c.5630A>G
p.Asn1877Ser
Unknown
GEN327R162
missense_variant
c.5630A>G
p.Asn1877Ser
Unknown
GEN327R163
missense_variant
c.5710C>T
p.Arg1904Cys
Familial
Paternal
Simplex
GEN327R164
stop_gained
c.2791C>T
p.Arg931Ter
De novo
Simplex
GEN327R165
stop_gained
c.3226A>T
p.Lys1076Ter
De novo
Simplex
GEN327R166
missense_variant
c.2952C>G
p.Asn984Lys
De novo
Simplex
GEN327R167
frameshift_variant
c.4304del
p.Gly1435ValfsTer6
De novo
GEN327R168
missense_variant
c.1588C>T
p.Arg530Trp
De novo
GEN327R169
missense_variant
c.5473C>T
p.Arg1825Trp
Familial
Maternal
GEN327R170
missense_variant
c.5597G>A
p.Arg1866Gln
Familial
Maternal
GEN327R171
missense_variant
c.491C>T
p.Thr164Met
Unknown
GEN327R172
missense_variant
c.4414G>A
p.Gly1472Arg
Unknown
GEN327R173
missense_variant
c.4082C>T
p.Ser1361Phe
Unknown
GEN327R174
frameshift_variant
c.2498del
p.Ser833IlefsTer2
Unknown
GEN327R175
splice_site_variant
c.4136A>C
p.Tyr1379Ser
Unknown
GEN327R176
stop_gained
c.4330C>T
p.Gln1444Ter
Unknown
GEN327R177
stop_gained
c.5335C>T
p.Arg1779Ter
Unknown
GEN327R178
missense_variant
c.5587C>T
p.Arg1863Cys
Unknown
GEN327R179
missense_variant
c.5597G>A
p.Arg1866Gln
Unknown
GEN327R180
missense_variant
c.473C>T
p.Ser158Leu
Unknown
GEN327R181
missense_variant
c.2327C>T
p.Pro776Leu
Unknown
GEN327R182
missense_variant
c.3562C>T
p.Arg1188Trp
Unknown
GEN327R183
missense_variant
c.4727G>A
p.Arg1576Gln
Unknown
GEN327R184
frameshift_variant
c.1940_1957delins
p.Gly647ValfsTer18
Unknown
Simplex
GEN327R185
missense_variant
c.641G>A
p.Gly214Asp
De novo
Simplex
GEN327R186
missense_variant
c.2936C>T
p.Ser979Phe
Unknown
GEN327R187
missense_variant
c.2060A>G
p.Gln687Arg
Familial
Paternal
GEN327R188
missense_variant
c.1243G>A
p.Glu415Lys
Unknown
GEN327R189
frameshift_variant
c.3941del
p.Tyr1314SerfsTer38
De novo
Simplex
GEN327R190
missense_variant
c.4850G>A
p.Arg1617Gln
Unknown
GEN327R191
missense_variant
c.5528A>G
p.His1843Arg
Unknown
GEN327R192
missense_variant
c.779T>C
p.Phe260Ser
Unknown
GEN327R193
missense_variant
c.752T>C
p.Leu251Pro
De novo
GEN327R194
missense_variant
c.4205G>A
p.Gly1402Glu
Unknown
GEN327R195
missense_variant
c.2806G>A
p.Glu936Lys
De novo
GEN327R196
missense_variant
c.3979A>G
p.Ile1327Val
De novo
Simplex
GEN327R197
missense_variant
c.515A>T
p.Glu172Val
Familial
Maternal
GEN327R198
frameshift_variant
c.57del
p.Glu20SerfsTer70
Unknown
Not maternal
GEN327R199
missense_variant
c.3893T>C
p.Leu1298Pro
De novo
Simplex
GEN327R200
missense_variant
c.1622C>A
p.Ser541Tyr
De novo
Simplex
GEN327R201
missense_variant
c.1588C>T
p.Arg530Trp
Unknown
GEN327R202
missense_variant
c.5630A>G
p.Asn1877Ser
De novo
GEN327R203
missense_variant
c.779T>C
p.Phe260Ser
De novo
GEN327R204
missense_variant
c.5506A>G
p.Met1836Val
De novo
GEN327R205
missense_variant
c.5281T>C
p.Tyr1761His
De novo
Simplex
GEN327R206
missense_variant
c.2533T>C
p.Ser845Pro
De novo
GEN327R207
missense_variant
c.4382G>T
p.Gly1461Val
De novo
GEN327R208
missense_variant
c.4911T>G
p.Ile1637Met
Familial
Paternal
GEN327R209
stop_gained
c.3652G>T
p.Glu1218Ter
Familial
Paternal
GEN327R210
missense_variant
c.2585A>G
p.Asn862Ser
Familial
Paternal
GEN327R211
missense_variant
c.4337A>G
p.Glu1446Gly
De novo
GEN327R212
splice_site_variant
c.614+1G>A
De novo
Simplex
GEN327R213
missense_variant
c.4499C>T
p.Pro1500Leu
Familial
Maternal
Extended multiplex
GEN327R214
missense_variant
c.4877G>A
p.Arg1626His
Unknown
Simplex
GEN327R215
missense_variant
c.4355C>T
p.Ser1452Phe
Unknown
Simplex
GEN327R216
missense_variant
c.4922T>G
p.Leu1641Arg
Unknown
Simplex
GEN327R217
missense_variant
c.2952C>G
p.Asn984Lys
Unknown
Simplex
GEN327R218
stop_gained
c.5887G>T
p.Glu1963Ter
Unknown
Simplex
GEN327R219
missense_variant
c.5606T>C
p.Met1869Thr
Familial
Maternal
Simplex
GEN327R220
missense_variant
c.1103C>T
p.Thr368Ile
Familial
Paternal
Multiplex
GEN327R221
missense_variant
c.1238C>A
p.Ala413Asp
De novo
GEN327R222
missense_variant
c.5630A>G
p.Asn1877Ser
Familial
Paternal
Multiplex
GEN327R223
missense_variant
c.4447G>A
p.Glu1483Lys
De novo
GEN327R224
missense_variant
c.971G>A
p.Cys324Tyr
De novo
Unknown
GEN327R225
missense_variant
c.773C>T
p.Thr258Ile
De novo
Simplex
GEN327R226
missense_variant
c.986A>G
p.Asp329Gly
De novo
Simplex
GEN327R227
missense_variant
c.760G>A
p.Val254Met
Unknown
GEN327R228
missense_variant
c.2546T>A
p.Leu849His
De novo
GEN327R229
missense_variant
c.641G>A
p.Gly214Asp
Unknown
GEN327R230
frameshift_variant
c.844_845del
p.Val282CysfsTer12
Unknown
GEN327R231
missense_variant
c.5257T>G
p.Ser1753Ala
De novo
GEN327R232
missense_variant
c.2803G>T
p.Gly935Trp
Unknown
GEN327R233
missense_variant
c.3259A>G
p.Ile1087Val
Unknown
GEN327R234
missense_variant
c.2549G>A
p.Arg850Gln
Unknown
GEN327R235a
missense_variant
c.4601C>T
p.Thr1534Met
Familial
Maternal
Simplex
GEN327R235b
frameshift_variant
c.4137del
p.Gln1379HisfsTer12
Familial
Paternal
Simplex
GEN327R236
missense_variant
c.641G>A
p.Gly214Asp
Unknown
Simplex
GEN327R237
missense_variant
c.5710C>T
p.Arg1904Cys
Unknown
No Common Variants Available
Summary Statistics:
Model Summary
Link between ion channel variants and monogenic seizures.
References
Primary
Neuronal voltage-gated ion channels are genetic modifiers of generalized epilepsy with febrile seizures plus.
Additional
Autistic-like behavior, spontaneous seizures, and increased neuronal excitability in a Scn8a mouse model
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Targeted knock out of Scn8a gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: C57BL/6J
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Using CRISPR/Cas9 technology, the human R1620L mutation was introduced into the equivalent location of the mouse Scn8a gene (R1618 in the mouse) on the C57BL/6J background (MGI:7470853).
Allele Type: ASD mutation
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: N/A
Mutant ES Cell Line:
Model Source: Andrew Escayg (Emory University)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Using CRISPR/Cas9 technology, the human R1620L mutation was introduced into the equivalent location of the mouse Scn8a gene (R1618 in the mouse) on the C57BL/6J background (MGI:7470853).
Allele Type: ASD mutation
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: N/A
Mutant ES Cell Line:
Model Source: Andrew Escayg (Emory University)
Increased
View More
Description: Exp Paradigm:
Maximal electroconvulsive seizure threshold test
Unreported
Not Reported:
Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Sensory, Social behavior
Increased
View More
Description:
General observations
P15-P22
Decreased
View More
Description:
Observation of thermally induced seizures
P13-P14
Decreased
View More
Description:
Body weight measurement
P15-P22
Mortality/lethality: postnatal1
Increased
View More
Description:
Survival analysis
P0-P22
No change
Western blot
P21-P22
Not Reported:
General locomotor activity: ambulatory activity1
Increased
View More
Description:
Open field test
3-4 months
Action potential property: threshold1
Decreased
View More
Description: Exp Paradigm:
Whole-cell current clamp
2 months
Action potential property: amplitude1
Increased
View More
Description: Exp Paradigm:
In vivo local field potential (LFP) recordings
Not reported
Action potential property: half-width1
Increased
View More
Description: Exp Paradigm:
Whole-cell current clamp
2 months
Action potential property: firing rate1
Decreased
View More
Description: Exp Paradigm:
Whole-cell current clamp
2 months
Increased
View More
Description: Exp Paradigm:
In vivo local field potential (LFP) recordings
Not reported
Action potential property: firing rate1
Decreased
View More
Description: Exp Paradigm:
In vivo local field potential (LFP) recordings
Not reported
Vertical jumping or back flipping1
Increased
View More
Description:
Novel cage test
3-4 months
Decreased
View More
Description:
Observation of thermally induced seizures
P13-P14, P21-P23
Increased
View More
Description:
Electroencephalogram (EEG)
3-5 months
Decreased
View More
Description: Exp Paradigm:
Observation of electrically induced seizures
2-4 months
Decreased
View More
Description: Exp Paradigm:
Observation of chemically induced seizures
2-4 months
Decreased
View More
Description:
Reciprocal social interaction test
3-4 months
Decreased
View More
Description:
Three-chamber social approach test
3-4 months
Mortality/lethality: life span: incomplete penetrance1
Increased
View More
Description:
Survival analysis
P0-P90
Decreased
View More
Description:
Fear conditioning test
3-4 months
Cued or contextual fear conditioning: memory of cue1
Decreased
View More
Description:
Fear conditioning test
3-4 months
Cued or contextual fear conditioning: memory of context1
Decreased
View More
Description:
Fear conditioning test
3-4 months
Object recognition memory1
Decreased
View More
Description:
Novel object recognition test
3-4 months
No change
Open field test
3-4 months
No change
Light-dark exploration test
3-4 months
Exploratory activity: habituation1 No change
Novel cage test
3-4 months
No change
Local inflammatory reaction
3-4 months
No change
Western blot
P21-P22
Motor coordination and balance1 No change
Accelerating rotarod test
3-4 months
No change
Sciatic nerve recording
P14-P15
Pain or nociception: mechanical1 No change
Von Frey filament test
3-4 months
Pain or nociception: thermal1 No change
Hot plate test
3-4 months
No change
Three-chamber social approach test
3-4 months
Not Reported:
Summary Statistics:
Show all nodes
Hide non-ASD
Interactor Symbol
Interactor Name
Interactor Organism
Entrez ID
Uniprot ID
Interaction Type
Evidence
Reference
ANK3
ankyrin 3, node of Ranvier (ankyrin G)
288
Q12955
in silico target prediction
Gasser A , et al. 2012
APP
amyloid beta (A4) precursor protein
351
P05067
IP/WB; Co-localization; Proximity ligation assay
Liu C , et al. 2015
FGF13
fibroblast growth factor 13
2258
Q92913
Y2H; IP/WB
Wittmack EK , et al. 2004
FGF14
fibroblast growth factor 14
2259
Q92915
Luciferase reporter assay
Shavkunov A , et al. 2012
FMR1
fragile X mental retardation 1
14265
P35922
HITS-CLIP
Darnell JC , et al. 2011
Mtap1b
microtubule-associated protein 1B
17755
P14873
Y2H; IP/WB
O'Brien JE , et al. 2012
Nedd4
neural precursor cell expressed, developmentally down-regulated 4
17999
P46935
Far Western Blot
Fotia AB , et al. 2004
Nedd4l
neural precursor cell expressed, developmentally down-regulated gene 4-like
83814
E9PXB7
Far Western Blot
Fotia AB , et al. 2004
Rbfox1
RNA binding protein, fox-1 homolog (C. elegans) 1
268859
Q9JJ43
qRT-PCR
O'Brien JE , et al. 2011
Scnm1-ps
sodium channel modifier 1, pseudogene
69269
Q8K136
qRT-PCR
Howell VM , et al. 2007
Gnao1
guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O
50664
P59215
IP/WB
Anis Y , et al. 1999
Mapk14
mitogen activated protein kinase 14
81649
Q56A33
IP/WB; in vitro kinase assay
Wittmack EK , et al. 2005
Scn1b
sodium channel, voltage-gated, type I, beta
29686
Q00954
IP; EMSA; in situ hybridization
Hartshorne RP , et al. 1982
Scn2b
sodium channel, voltage-gated, type II, beta
25349
P54900
IP; EMSA
Hartshorne RP , et al. 1982
