SCN2A
sodium voltage-gated channel alpha subunit 2, the group of Sodium voltage-gated channel alpha subunits
Basic information
Region (hg38): 2:165194993-165392310
Previous symbols: [ "SCN2A1", "SCN2A2" ]
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy, 11 (Definitive), mode of inheritance: AD
- seizures, benign familial infantile, 3 (Strong), mode of inheritance: AD
- genetic developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
- infantile spasms (Supportive), mode of inheritance: AD
- benign familial infantile epilepsy (Supportive), mode of inheritance: AD
- Dravet syndrome (Supportive), mode of inheritance: AD
- benign familial neonatal-infantile seizures (Supportive), mode of inheritance: AD
- malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
- complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
- episodic ataxia, type 9 (Strong), mode of inheritance: AD
- seizures, benign familial infantile, 3 (Strong), mode of inheritance: AD
- developmental and epileptic encephalopathy, 11 (Strong), mode of inheritance: AD
- complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
- intellectual disability (Definitive), mode of inheritance: AD
- developmental and epileptic encephalopathy, 11 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Developmental and epileptic encephalopathy 11; Seizures, benign familial infantile, 3; Episodic ataxia, type 9 | AD | Neurologic | In Epileptic encephalopathy, early infantile, 11 and Seizures, benign familial infantile, 3, individuals may manifest with seizures (among other findings), and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology; In Episodic ataxia, type 9, individuals manifest with ataxic episodes, and treatment with acetazolamide has been reported to be effective in some patients | Neurologic | 6660252; 3508699; 8734025; 11326335; 15048894; 15028761; 19786696; 20956790; 22029951; 22591750; 22612257; 23020937; 26645390; 28331464; 30415926; 30643928; 30870728; 30928199; 31487502 |
ClinVar
This is a list of variants' phenotypes submitted to
- Developmental_and_epileptic_encephalopathy,_11 (1866 variants)
- Seizures,_benign_familial_infantile,_3 (1792 variants)
- not_provided (1023 variants)
- Inborn_genetic_diseases (282 variants)
- not_specified (186 variants)
- Complex_neurodevelopmental_disorder (101 variants)
- SCN2A-related_disorder (88 variants)
- Episodic_ataxia,_type_9 (72 variants)
- Developmental_and_epileptic_encephalopathy (34 variants)
- West_syndrome (24 variants)
- Intellectual_disability (17 variants)
- Seizure (15 variants)
- Early_Infantile_Epileptic_Encephalopathy,_Autosomal_Dominant (13 variants)
- See_cases (11 variants)
- Benign_familial_infantile_epilepsy (9 variants)
- Epileptic_encephalopathy (8 variants)
- SCN2A-related_generalized_epilepsy_with_febrile_seizures_plus (6 variants)
- Autism_spectrum_disorder (5 variants)
- Infantile_spasms (5 variants)
- Epilepsy_of_infancy_with_migrating_focal_seizures (5 variants)
- unclassified_developmental_and_epileptic_encephalopathy (4 variants)
- Autism (4 variants)
- Developmental_disorder (4 variants)
- Lennox-Gastaut_syndrome (3 variants)
- Genetic_developmental_and_epileptic_encephalopathy (3 variants)
- Febrile_seizure_(within_the_age_range_of_3_months_to_6_years) (3 variants)
- Non-syndromic_intellectual_disability (3 variants)
- Neurodevelopmental_disorder (2 variants)
- Neurodevelopmental_delay (2 variants)
- Developmental_and_epileptic_encephalopathy,_1 (2 variants)
- Epilepsy_with_myoclonic_atonic_seizures (2 variants)
- Self-limited_epilepsy_with_centrotemporal_spikes (2 variants)
- benign_sporadic_infantile_epilepsy (2 variants)
- Benign_familial_neonatal-infantile_seizures_1 (2 variants)
- Malignant_migrating_partial_seizures_of_infancy (2 variants)
- Global_developmental_delay (2 variants)
- Continuous_spikes_and_waves_during_sleep (2 variants)
- Hemiplegia/hemiparesis (1 variants)
- Vertigo (1 variants)
- Benign_Neonatal_Epilepsy (1 variants)
- Focal_epilepsy (1 variants)
- Intellectual_disability,_autosomal_dominant (1 variants)
- SCN2A-related_neurodevelopmental_disorder (1 variants)
- History_of_neurodevelopmental_disorder (1 variants)
- Developmental_and_epileptic_encephalopathy,_12 (1 variants)
- Dystonia_12 (1 variants)
- SCN2A-associated_neurodevelopmental_disorders (1 variants)
- Severe_myoclonic_epilepsy_in_infancy (1 variants)
- SCN2A-mediated_disorder (1 variants)
- benign_sporadic_neonatal-infantile_epilepsy (1 variants)
- Hereditary_episodic_ataxia (1 variants)
- intellectual_deficiency (1 variants)
- Epilepsy (1 variants)
- Abnormal_cerebral_morphology (1 variants)
- Movement_disorder (1 variants)
- Marfanoid_habitus_and_intellectual_disability (1 variants)
- Pulmonary_fibrosis_and/or_bone_marrow_failure,_Telomere-related,_3 (1 variants)
- Epileptic_encephalopathy,_infantile_or_early_childhood (1 variants)
- Myoclonus (1 variants)
- Developmental_and_epileptic_encephalopathy,_76 (1 variants)
- Autism_Spectrum_Disorder_with_Intellectual_Disability (1 variants)
- Pyridoxine-dependent_epilepsy (1 variants)
- Spastic_ataxia (1 variants)
- Developmental_and_epileptic_encephalopathy,_30 (1 variants)
- Generalized_epilepsy_with_febrile_seizures_plus (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN2A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001040142.2. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 19 | 499 | 14 | 533 | ||
| missense | 134 | 302 | 1073 | 70 | 1583 | |
| nonsense | 60 | 22 | 85 | |||
| start loss | 1 | 1 | 2 | |||
| frameshift | 98 | 27 | 132 | |||
| splice donor/acceptor (+/-2bp) | 24 | 20 | 45 | |||
| Total | 317 | 373 | 1103 | 569 | 18 |
Highest pathogenic variant AF is 0.00002395049
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SCN2A | protein_coding | protein_coding | ENST00000357398 | 26 | 152907 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.55e-10 | 125727 | 0 | 4 | 125731 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 6.46 | 469 | 1.06e+3 | 0.442 | 0.0000572 | 13382 |
| Missense in Polyphen | 126 | 481.11 | 0.2619 | 6144 | ||
| Synonymous | -0.127 | 374 | 371 | 1.01 | 0.0000205 | 3708 |
| Loss of Function | 7.92 | 5 | 82.7 | 0.0605 | 0.00000468 | 1036 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.00000882 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000329 | 0.000326 |
dbNSFP
Source:
- 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, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. {ECO:0000269|PubMed:1325650, ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:28256214}.;
- Disease
- DISEASE: Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant. {ECO:0000269|PubMed:11371648, ECO:0000269|PubMed:12243921, ECO:0000269|PubMed:15048894, ECO:0000269|PubMed:16417554, ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:17386050, ECO:0000269|PubMed:18479388, ECO:0000269|PubMed:20371507, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:23758435, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26291284}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 11 (EIEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neruon excitability are associated with ASD. {ECO:0000269|PubMed:28256214}.;
- 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
- 0.344
Intolerance Scores
- loftool
- 0.00145
- rvis_EVS
- -1.99
- rvis_percentile_EVS
- 1.77
Haploinsufficiency Scores
- pHI
- 0.646
- hipred
- Y
- hipred_score
- 0.778
- ghis
- 0.624
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.710
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Scn2a
- Phenotype
- growth/size/body region phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- sodium ion transport;intrinsic apoptotic signaling pathway in response to osmotic stress;neuronal action potential;regulation of ion transmembrane transport;sodium ion transmembrane transport;myelination;neuron apoptotic process;membrane depolarization during action potential
- Cellular component
- voltage-gated sodium channel complex;plasma membrane;integral component of plasma membrane;intercalated disc;T-tubule;axon;intrinsic component of plasma membrane;node of Ranvier;paranode region of axon;sodium channel complex;glutamatergic synapse;integral component of presynaptic membrane
- Molecular function
- voltage-gated ion channel activity;voltage-gated sodium channel activity