SCN3A

sodium voltage-gated channel alpha subunit 3, the group of Sodium voltage-gated channel alpha subunits

Basic information

Region (hg38): 2:165087526-165204050

Links

ENSG00000153253NCBI:6328OMIM:182391HGNC:10590Uniprot:Q9NY46AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
  • genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
  • developmental and epileptic encephalopathy, 62 (Strong), mode of inheritance: AD
  • epilepsy, familial focal, with variable foci 4 (Strong), mode of inheritance: AD
  • genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
  • epilepsy, familial focal, with variable foci 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Epilepsy, familial focal, with variable foci 4; Developmental and epileptic encephalopathy 62ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic24157691; 29466837
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN3A gene.

  • not_provided (1823 variants)
  • Inborn_genetic_diseases (152 variants)
  • Developmental_and_epileptic_encephalopathy,_62 (74 variants)
  • Epilepsy,_familial_focal,_with_variable_foci_4 (58 variants)
  • SCN3A-related_disorder (49 variants)
  • not_specified (16 variants)
  • Developmental_and_epileptic_encephalopathy (5 variants)
  • Seizure (5 variants)
  • See_cases (3 variants)
  • Epilepsy (2 variants)
  • SCN3A-related_neurodevelopmental_disorder (2 variants)
  • SCN3A-related_neurodevelopmental_sisorder (2 variants)
  • Neurodevelopmental_disorder (1 variants)
  • atypical_cerebral_palsy (1 variants)
  • Congenital_bilateral_perisylvian_syndrome (1 variants)
  • Epilepsy,_focal,_SCN3A_related (1 variants)
  • Polymicrogyria (1 variants)
  • Epilepsy,_idiopathic_generalized,_susceptibility_to,_7 (1 variants)
  • Developmental_delay (1 variants)
  • Epilepsy,_familial_focal,_with_variable_foci_1 (1 variants)
  • Neurodevelopmental_abnormality (1 variants)
  • Developmental_and_epileptic_encephalopathy,_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN3A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006922.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
11
clinvar
455
clinvar
15
clinvar
481
missense
3
clinvar
28
clinvar
983
clinvar
87
clinvar
3
clinvar
1104
nonsense
2
clinvar
27
clinvar
29
start loss
0
frameshift
1
clinvar
4
clinvar
23
clinvar
28
splice donor/acceptor (+/-2bp)
3
clinvar
7
clinvar
10
Total 6 35 1051 542 18

Highest pathogenic variant AF is 0.0000218898

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCN3Aprotein_codingprotein_codingENST00000283254 26116546
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.003.05e-81257280201257480.0000795
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense4.626291.05e+30.5990.000055513365
Missense in Polyphen299563.360.530747247
Synonymous-1.244013711.080.00002043695
Loss of Function7.63883.10.09630.000004761032

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004780.000416
Ashkenazi Jewish0.00009930.0000992
East Asian0.000.00
Finnish0.00009250.0000924
European (Non-Finnish)0.00005350.0000527
Middle Eastern0.000.00
South Asian0.000.00
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:24157691, PubMed:28235671, PubMed:29466837). May contribute to the regulation of serotonin/5-hydroxytryptamine release by enterochromaffin cells (By similarity). In pancreatic endocrine cells, required for both glucagon and glucose-induced insulin secretion (By similarity). {ECO:0000250|UniProtKB:A2ASI5, ECO:0000269|PubMed:24157691, ECO:0000269|PubMed:28235671, ECO:0000269|PubMed:29466837}.;
Disease
DISEASE: Epilepsy, familial focal, with variable foci 4 (FFEVF4) [MIM:617935]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete. FFEVF4 is characterized by onset of focal seizures in the first years of life. {ECO:0000269|PubMed:24157691, ECO:0000269|PubMed:28235671}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 62 (EIEE62) [MIM:617938]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE62 is characterized by onset of seizures in the first year of life. {ECO:0000269|PubMed:29466837}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Taste transduction - Homo sapiens (human);Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

pRec
0.106

Intolerance Scores

loftool
0.00586
rvis_EVS
-2.48
rvis_percentile_EVS
0.97

Haploinsufficiency Scores

pHI
0.587
hipred
Y
hipred_score
0.809
ghis
0.621

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.881

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scn3a
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
sodium ion transport;neuronal action potential;regulation of ion transmembrane transport;sodium ion transmembrane transport;membrane depolarization during action potential
Cellular component
voltage-gated sodium channel complex;cytoplasm;plasma membrane;axon
Molecular function
voltage-gated ion channel activity;voltage-gated sodium channel activity