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GeneBe

SCN1A

sodium voltage-gated channel alpha subunit 1, the group of Sodium voltage-gated channel alpha subunits

Basic information

Region (hg38): 2:165984640-166149214

Previous symbols: [ "SCN1", "FEB3" ]

Links

ENSG00000144285 ∙ NCBI:6323 ∙ OMIM:182389 ∙ HGNC:10585 ∙ Uniprot:P35498 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • developmental and epileptic encephalopathy, 6 (Definitive), mode of inheritance: AD
  • arthrogryposis (Moderate), mode of inheritance: AD
  • developmental and epileptic encephalopathy, 6 (Definitive), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus, type 2 (Definitive), mode of inheritance: AD
  • migraine, familial hemiplegic, 3 (Strong), mode of inheritance: AD
  • developmental and epileptic encephalopathy, 6 (Definitive), mode of inheritance: AD
  • Lennox-Gastaut syndrome (Supportive), mode of inheritance: AD
  • myoclonic-astatic epilepsy (Supportive), mode of inheritance: Unknown
  • familial or sporadic hemiplegic migraine (Supportive), mode of inheritance: AD
  • Dravet syndrome (Supportive), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus (Supportive), mode of inheritance: AD
  • malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
  • migraine, familial hemiplegic, 3 (Strong), mode of inheritance: AD
  • developmental and epileptic encephalopathy, 6 (Strong), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus, type 2 (Strong), mode of inheritance: AD
  • developmental and epileptic encephalopathy (Strong), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus (Definitive), mode of inheritance: AD
  • Dravet syndrome (Definitive), mode of inheritance: AD
  • familial hemiplegic migraine (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Migraine, familial hemiplegic 3ADNeurologic; PharmacogenomicVasoconstricting agents (due to risk of stroke) and cerebral angiography (due to risk of precipitation of attack) should be avoidedNeurologic10486327; 10852559; 10742094; 11524484; 15277634; 16054936; 16326807; 16505326; 17190949; 17347258; 20301562; 19522081; 19332696; 28331464
For 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 SCN1A gene.

  • Early infantile epileptic encephalopathy with suppression bursts (2612 variants)
  • not provided (1347 variants)
  • Severe myoclonic epilepsy in infancy (605 variants)
  • Generalized epilepsy with febrile seizures plus, type 2 (280 variants)
  • Inborn genetic diseases (223 variants)
  • not specified (198 variants)
  • Migraine, familial hemiplegic, 3 (129 variants)
  • Epilepsy (63 variants)
  • Seizure (28 variants)
  • Developmental and epileptic encephalopathy 6B (27 variants)
  • Generalized epilepsy with febrile seizures plus, type 1 (23 variants)
  • SCN1A-related condition (18 variants)
  • Autosomal dominant epilepsy (15 variants)
  • Familial hemiplegic migraine (9 variants)
  • Severe myoclonic epilepsy in infancy;Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2 (9 variants)
  • See cases (8 variants)
  • Intellectual disability (8 variants)
  • Migraine, familial hemiplegic, 3;Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2 (8 variants)
  • Epileptic encephalopathy (7 variants)
  • Developmental and epileptic encephalopathy, 6 (6 variants)
  • Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy;Migraine, familial hemiplegic, 3 (5 variants)
  • Severe myoclonic epilepsy in infancy;Developmental and epileptic encephalopathy 6B;Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2 (5 variants)
  • Severe myoclonic epilepsy in infancy;Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2;Developmental and epileptic encephalopathy 6B (4 variants)
  • Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy (4 variants)
  • Generalized epilepsy (4 variants)
  • SCN1A Seizure Disorders (4 variants)
  • Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2 (4 variants)
  • Migraine, familial hemiplegic, 3;Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2;Developmental and epileptic encephalopathy 6B (3 variants)
  • SCN1A-related conditions (3 variants)
  • Developmental and epileptic encephalopathy 6B;Severe myoclonic epilepsy in infancy;Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2 (3 variants)
  • Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2;Developmental and epileptic encephalopathy 6B (3 variants)
  • Migraine, familial hemiplegic, 3;Severe myoclonic epilepsy in infancy;Developmental and epileptic encephalopathy 6B;Generalized epilepsy with febrile seizures plus, type 2 (3 variants)
  • Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy (3 variants)
  • Generalized epilepsy with febrile seizures plus (3 variants)
  • Focal epilepsy (3 variants)
  • Generalized epilepsy with febrile seizures plus, type 2;Migraine, familial hemiplegic, 3;Severe myoclonic epilepsy in infancy (2 variants)
  • Seizure;Global developmental delay (2 variants)
  • 11 conditions (2 variants)
  • SUDDEN INFANT DEATH SYNDROME (2 variants)
  • Febrile seizures, familial, 3a (2 variants)
  • Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2;Developmental and epileptic encephalopathy 6B;Migraine, familial hemiplegic, 3 (2 variants)
  • Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy;Migraine, familial hemiplegic, 3;Developmental and epileptic encephalopathy 6B (2 variants)
  • Severe myoclonic epilepsy in infancy;Developmental and epileptic encephalopathy 6B (2 variants)
  • Childhood epilepsy with centrotemporal spikes (2 variants)
  • Migraine, familial hemiplegic, 3;Developmental and epileptic encephalopathy 6B;Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2 (2 variants)
  • Developmental and epileptic encephalopathy 6B;Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy;Migraine, familial hemiplegic, 3 (2 variants)
  • Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy;Developmental and epileptic encephalopathy 6B (2 variants)
  • Autism (2 variants)
  • West syndrome (2 variants)
  • Developmental and epileptic encephalopathy, 1 (2 variants)
  • Sudden unexplained death in childhood (2 variants)
  • Intellectual disability, mild;Seizure (1 variants)
  • Developmental and epileptic encephalopathy 6B;Migraine, familial hemiplegic, 3;Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2 (1 variants)
  • 7 conditions (1 variants)
  • Autosomal dominant SCN1A-related disorder (1 variants)
  • Microcephaly;Autism;Focal-onset seizure (1 variants)
  • Myoclonic encephalopathy (1 variants)
  • Microcephaly (1 variants)
  • Developmental and epileptic encephalopathy, 76 (1 variants)
  • SCN1A-related channelopathy (1 variants)
  • Severe myoclonic epilepsy in infancy;Early infantile epileptic encephalopathy with suppression bursts;Generalized epilepsy with febrile seizures plus;Familial hemiplegic migraine (1 variants)
  • Primary generalized epilepsy (1 variants)
  • Developmental and epileptic encephalopathy 6B;Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy (1 variants)
  • Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2;Migraine, familial hemiplegic, 3;Developmental and epileptic encephalopathy 6B (1 variants)
  • myoclonic epilepsy (1 variants)
  • carbamazepine response - Dosage (1 variants)
  • Seizure;Delayed speech and language development (1 variants)
  • Febrile seizures, familial, 1;Severe myoclonic epilepsy in infancy;Migraine, familial hemiplegic, 3;Generalized epilepsy with febrile seizures plus, type 2 (1 variants)
  • Neurodevelopmental disorder (1 variants)
  • Intellectual disability;Obesity;Seizure (1 variants)
  • Developmental and epileptic encephalopathy 6B;Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2 (1 variants)
  • Bilateral tonic-clonic seizure;Generalized non-motor (absence) seizure;Seizure (1 variants)
  • Focal impaired awareness seizure (1 variants)
  • Severe myoclonic epilepsy in infancy;Acute encephalopathy (1 variants)
  • pharmacoresistant multifocal epilepsy (1 variants)
  • Epilepsy;Severe myoclonic epilepsy in infancy (1 variants)
  • Developmental and epileptic encephalopathy 6B;Severe myoclonic epilepsy in infancy (1 variants)
  • Generalized epilepsy with febrile seizures plus, type 2;Severe myoclonic epilepsy in infancy;Developmental and epileptic encephalopathy 6B (1 variants)
  • Macrocephaly and epileptic encephalopathy (1 variants)
  • Seizure;Intellectual disability (1 variants)
  • Developmental and epileptic encephalopathy 6B;Severe myoclonic epilepsy in infancy;Generalized epilepsy with febrile seizures plus, type 2;Migraine, familial hemiplegic, 3 (1 variants)
  • 6 conditions (1 variants)
  • SCN1A-Related Disorders (1 variants)
  • Febrile seizure (within the age range of 3 months to 6 years) (1 variants)
  • Migraine, familial hemiplegic, 3;Severe myoclonic epilepsy in infancy;Febrile seizures, familial, 1;Generalized epilepsy with febrile seizures plus, type 2 (1 variants)
  • Seizure;Autism;Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN1A 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
1
clinvar
28
clinvar
365
clinvar
7
clinvar
 401
missense
334
clinvar
425
clinvar
976
clinvar
59
clinvar
5
clinvar
 1799
nonsense
222
clinvar
24
clinvar
5
clinvar
 251
start loss
1
clinvar
1
clinvar
 2
frameshift
396
clinvar
50
clinvar
9
clinvar
 455
inframe indel
13
clinvar
17
clinvar
21
clinvar
 51
splice donor/acceptor (+/-2bp)
106
clinvar
30
clinvar
3
clinvar
 139
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
16
18
55
48
1
 138
non coding
?
    UTR, intron and other, non coding variants
3
clinvar
3
clinvar
50
clinvar
261
clinvar
111
clinvar
 428
Total 1075 551 1092 685 123

Highest pathogenic variant AF is 0.0000132

Variants in SCN1A

This is a list of pathogenic ClinVar variants found in the SCN1A region.

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

Position Type Phenotype Significance ClinVar
2-165989256-G-A Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Jan 12, 2018)331855
2-165989284-G-A Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Benign/Likely benign (May 14, 2021)331856
2-165989293-A-G Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Benign/Likely benign (May 24, 2021)331857
2-165989295-C-T Migraine, familial hemiplegic, 3 • Epilepsy • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Jan 13, 2018)331858
2-165989372-GA-G Familial hemiplegic migraine • Epilepsy Conflicting classifications of pathogenicity (Oct 01, 2022)331859
2-165989381-A-T Migraine, familial hemiplegic, 3 • Epilepsy • Generalized epilepsy with febrile seizures plus, type 2 Conflicting classifications of pathogenicity (Nov 01, 2023)331860
2-165989450-C-T Migraine, familial hemiplegic, 3 • Epilepsy • Generalized epilepsy with febrile seizures plus, type 2 Conflicting classifications of pathogenicity (Jan 12, 2018)331861
2-165989451-G-A Generalized epilepsy with febrile seizures plus, type 2 • Migraine, familial hemiplegic, 3 Uncertain significance (Apr 28, 2017)893817
2-165989495-A-G Likely benign (May 19, 2021)1325975
2-165989506-G-A Migraine, familial hemiplegic, 3 • Epilepsy • Generalized epilepsy with febrile seizures plus, type 2 Benign (May 14, 2021)331862
2-165989552-T-C Migraine, familial hemiplegic, 3 • Epilepsy • Generalized epilepsy with febrile seizures plus, type 2 Benign/Likely benign (May 14, 2021)331863
2-165989592-G-A Migraine, familial hemiplegic, 3 • Epilepsy • Generalized epilepsy with febrile seizures plus, type 2 Benign/Likely benign (May 23, 2021)331864
2-165989763-C-T Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Jan 13, 2018)331865
2-165989879-T-A Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Jan 12, 2018)894730
2-165989920-C-T Generalized epilepsy with febrile seizures plus, type 2 • Migraine, familial hemiplegic, 3 Uncertain significance (Jan 12, 2018)894731
2-165989948-C-T Generalized epilepsy with febrile seizures plus, type 2 • Migraine, familial hemiplegic, 3 Uncertain significance (Jan 13, 2018)892748
2-165990021-C-T Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Benign/Likely benign (Jan 12, 2018)331866
2-165990093-T-C Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Jan 13, 2018)892749
2-165990101-C-G Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Mar 30, 2018)892750
2-165990120-A-C Generalized epilepsy with febrile seizures plus, type 2 • Migraine, familial hemiplegic, 3 Uncertain significance (Jan 13, 2018)893545
2-165990124-A-G Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Jan 12, 2018)331867
2-165990214-T-A Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Likely benign (Apr 27, 2017)331868
2-165990220-A-G Epilepsy • Migraine, familial hemiplegic, 3 • Generalized epilepsy with febrile seizures plus, type 2 Benign/Likely benign (Jan 12, 2018)331869
2-165990268-A-G Migraine, familial hemiplegic, 3 • Epilepsy • Generalized epilepsy with febrile seizures plus, type 2 Uncertain significance (Jan 12, 2018)331870
2-165990319-G-A Generalized epilepsy with febrile seizures plus, type 2 • Migraine, familial hemiplegic, 3 Uncertain significance (Mar 30, 2018)893842

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCN1Aprotein_codingprotein_codingENST00000303395 26138854
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.002.05e-13125733051257380.0000199
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense5.225901.07e+30.5510.000058113399
Missense in Polyphen189532.140.355176820
Synonymous0.8763643860.9430.00002243751
Loss of Function8.52288.50.02260.000005641020

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00006160.0000615
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00002650.0000264
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.000.00

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, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. Plays a key role in brain, probably by regulating the moment when neurotransmitters are released in neurons. Involved in sensory perception of mechanical pain: activation in somatosensory neurons induces pain without neurogenic inflammation and produces hypersensitivity to mechanical, but not thermal stimuli. {ECO:0000250|UniProtKB:A2APX8}.;
Disease
DISEASE: Generalized epilepsy with febrile seizures plus 2 (GEFS+2) [MIM:604403]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. {ECO:0000269|PubMed:10742094, ECO:0000269|PubMed:11254444, ECO:0000269|PubMed:11254445, ECO:0000269|PubMed:11524484, ECO:0000269|PubMed:11756608, ECO:0000269|PubMed:12535936, ECO:0000269|PubMed:12576172, ECO:0000269|PubMed:12919402, ECO:0000269|PubMed:14672992, ECO:0000269|PubMed:15525788, ECO:0000269|PubMed:15694566, ECO:0000269|PubMed:15715999, ECO:0000269|PubMed:16525050, ECO:0000269|PubMed:17347258, ECO:0000269|PubMed:17507202, ECO:0000269|PubMed:17561957, ECO:0000269|PubMed:17927801, ECO:0000269|PubMed:17928445, ECO:0000269|PubMed:18251839, ECO:0000269|PubMed:18413471, ECO:0000269|PubMed:18566737, ECO:0000269|PubMed:19339291, ECO:0000269|PubMed:19464195, ECO:0000269|PubMed:19522081, ECO:0000269|PubMed:20117752, ECO:0000269|PubMed:20550552, ECO:0000269|PubMed:20600615, ECO:0000269|PubMed:20729507, ECO:0000269|PubMed:21248271, ECO:0000269|PubMed:21864321}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 6 (EIEE6) [MIM:607208]: A severe form of epileptic encephalopathy characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development delay is observed around the second year of life. Some patients manifest a borderline disease phenotype and do not necessarily fulfill all diagnostic criteria for core EIEE6. EIEE6 is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus. {ECO:0000269|PubMed:11359211, ECO:0000269|PubMed:12083760, ECO:0000269|PubMed:12566275, ECO:0000269|PubMed:12754708, ECO:0000269|PubMed:12821740, ECO:0000269|PubMed:14504318, ECO:0000269|PubMed:14672992, ECO:0000269|PubMed:14738421, ECO:0000269|PubMed:15087100, ECO:0000269|PubMed:15944908, ECO:0000269|PubMed:16122630, ECO:0000269|PubMed:16458823, ECO:0000269|PubMed:16713920, ECO:0000269|PubMed:17054684, ECO:0000269|PubMed:17054685, ECO:0000269|PubMed:17129991, ECO:0000269|PubMed:17347258, ECO:0000269|PubMed:17561957, ECO:0000269|PubMed:18413471, ECO:0000269|PubMed:18639757, ECO:0000269|PubMed:18930999, ECO:0000269|PubMed:19522081, ECO:0000269|PubMed:19563458, ECO:0000269|PubMed:19589774, ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:20110217, ECO:0000269|PubMed:20431604, ECO:0000269|PubMed:20452746, ECO:0000269|PubMed:20522430, ECO:0000269|PubMed:20729507, ECO:0000269|PubMed:21248271, ECO:0000269|PubMed:21864321, ECO:0000269|PubMed:22092154, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28544625}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Intractable childhood epilepsy with generalized tonic- clonic seizures (ICEGTC) [MIM:607208]: A disorder characterized by generalized tonic-clonic seizures beginning usually in infancy and induced by fever. Seizures are associated with subsequent mental decline, as well as ataxia or hypotonia. ICEGTC is similar to SMEI, except for the absence of myoclonic seizures. {ECO:0000269|PubMed:12566275, ECO:0000269|PubMed:16210358, ECO:0000269|PubMed:17507202, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23708187}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Migraine, familial hemiplegic, 3 (FHM3) [MIM:609634]: A subtype of migraine associated with transient blindness in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking. {ECO:0000269|PubMed:16054936, ECO:0000269|PubMed:17397047, ECO:0000269|PubMed:18021921, ECO:0000269|PubMed:19332696}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Febrile seizures, familial, 3A (FEB3A) [MIM:604403]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. {ECO:0000269|PubMed:16326807, ECO:0000269|PubMed:19522081}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=SCN1A mutations may be involved in Panayiotopoulos syndrome, a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an electroencephalogram that shows shifting and/or multiple foci, often with occipital predominance. Autonomic seizures in Panayiotopoulos syndrome consist of episodes of disturbed autonomic function with emesis as the predominant symptom. Cardiorespiratory arrest is exceptional. {ECO:0000269|PubMed:17679682, ECO:0000269|PubMed:19339291, ECO:0000269|PubMed:19522081}.;
Pathway
Dopaminergic synapse - 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
0.214

Intolerance Scores

loftool
0.000138
rvis_EVS
-1.43
rvis_percentile_EVS
4.03

Haploinsufficiency Scores

pHI
0.258
hipred
Y
hipred_score
0.740
ghis
0.565

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.727

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scn1a
Phenotype
growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal 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); reproductive system 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);

Zebrafish Information Network

Gene name
scn1laa
Affected structure
Rohon-Beard neuron
Phenotype tag
abnormal
Phenotype quality
membrane potential

Gene ontology

Biological process
sodium ion transport;adult walking behavior;neuronal action potential propagation;neuronal action potential;regulation of ion transmembrane transport;sodium ion transmembrane transport;neuromuscular process controlling posture;detection of mechanical stimulus involved in sensory perception of pain;cardiac muscle cell action potential involved in contraction;membrane depolarization during action potential
Cellular component
voltage-gated sodium channel complex;nucleoplasm;plasma membrane;intercalated disc;nuclear body;Z disc;T-tubule;axon;node of Ranvier;neuronal cell body;axon initial segment
Molecular function
voltage-gated ion channel activity;voltage-gated sodium channel activity