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GeneBe

SCN3A

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

Basic information

Region (hg38): 2:165087525-165204050

Links

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

Phenotypes

GenCC

Source: genCC

  • undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
  • developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
  • 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

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 (1391 variants)
  • Inborn genetic diseases (50 variants)
  • Developmental and epileptic encephalopathy, 62 (46 variants)
  • Epilepsy, familial focal, with variable foci 4 (29 variants)
  • Developmental and epileptic encephalopathy, 62;Epilepsy, familial focal, with variable foci 4 (18 variants)
  • SCN3A-related condition (14 variants)
  • not specified (13 variants)
  • See cases (3 variants)
  • SCN3A-related neurodevelopmental sisorder (2 variants)
  • SCN3A-related neurodevelopmental disorder (2 variants)
  • Early infantile epileptic encephalopathy with suppression bursts (1 variants)
  • SCN3A- Related Disorder (1 variants)
  • Polymicrogyria;Developmental delay (1 variants)
  • Epilepsy, idiopathic generalized, susceptibility to, 7 (1 variants)
  • Congenital bilateral perisylvian syndrome (1 variants)
  • Intellectual disability;Seizure (1 variants)
  • atypical cerebral palsy (1 variants)
  • Epilepsy, focal, SCN3A related;Developmental and epileptic encephalopathy, 62 (1 variants)
  • Neurodevelopmental disorder (1 variants)
  • Epilepsy, familial focal, with variable foci 1 (1 variants)
  • Intellectual disability (1 variants)
  • Epilepsy, familial focal, with variable foci 4;Developmental and epileptic encephalopathy, 62 (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.

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.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
12
clinvar
308
clinvar
19
clinvar
339
missense
1
clinvar
18
clinvar
723
clinvar
44
clinvar
3
clinvar
789
nonsense
2
clinvar
16
clinvar
18
start loss
0
frameshift
1
clinvar
2
clinvar
14
clinvar
17
inframe indel
1
clinvar
6
clinvar
1
clinvar
8
splice donor/acceptor (+/-2bp)
4
clinvar
4
splice region
23
41
1
65
non coding
6
clinvar
111
clinvar
50
clinvar
167
Total 4 21 781 463 73

Variants in SCN3A

This is a list of pathogenic ClinVar variants found in the SCN3A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
2-165090153-C-T Likely benign (Dec 20, 2023)2902159
2-165090155-T-C Uncertain significance (Oct 23, 2019)665545
2-165090155-T-G Uncertain significance (Nov 27, 2023)1968485
2-165090156-T-G Likely benign (Dec 25, 2023)800264
2-165090157-T-G Uncertain significance (Dec 06, 2023)403874
2-165090160-T-C Uncertain significance (May 06, 2021)1520898
2-165090162-TTC-T Uncertain significance (Feb 03, 2021)1435913
2-165090164-C-A Uncertain significance (Jul 25, 2022)2413097
2-165090166-C-G Uncertain significance (Aug 10, 2022)1429785
2-165090169-A-T Uncertain significance (Dec 30, 2023)1720758
2-165090170-C-T Uncertain significance (Jun 30, 2021)1331216
2-165090178-C-A Uncertain significance (Nov 15, 2022)1720543
2-165090183-G-C Uncertain significance (Sep 26, 2022)2446096
2-165090185-T-C Uncertain significance (Sep 27, 2022)1977509
2-165090188-C-T Uncertain significance (Jan 03, 2024)2161211
2-165090197-G-T Uncertain significance (Dec 04, 2019)863826
2-165090201-G-A not specified • SCN3A-related condition Benign/Likely benign (Feb 01, 2024)498232
2-165090204-T-C Likely benign (Aug 31, 2022)1110316
2-165090206-T-C Uncertain significance (Aug 09, 2022)1063741
2-165090206-T-G Developmental and epileptic encephalopathy, 62 • Epilepsy, familial focal, with variable foci 1 Uncertain significance (Jun 22, 2022)1339140
2-165090213-C-T Likely benign (Sep 01, 2022)1565319
2-165090218-C-T Uncertain significance (May 27, 2022)2100233
2-165090224-C-G Uncertain significance (Dec 06, 2021)1396447
2-165090227-G-A Uncertain significance (Sep 07, 2022)2090092
2-165090227-G-GT Uncertain significance (Dec 27, 2023)2777605

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